Article

PDF
Access to the PDF text
Advertising


Free Article !

Archives of cardiovascular diseases
Volume 110, n° 1
pages 1-6 (janvier 2017)
Doi : 10.1016/j.acvd.2016.12.001
Received : 12 July 2016 ;  accepted : 5 December 2016
New guidelines, new recommendations! But what is really new? A pragmatic interpretation of the 2016 European guidelines for the management of chronic heart failure
Nouvelles recommandations ! Mais quelles nouveautés ? Une interprétation pragmatique des recommandations européennes 2016 de la prise en charge de l’insuffisance cardiaque chronique
 

Pascal de Groote a, b, , Ariel Cohen c, Yves Juillière d, Thibaud Damy e
a Service de cardiologie, pôle cardiovasculaire et pulmonaire, CHRU de Lille, 59037 Lille, France 
b Inserm U1167, institut Pasteur de Lille, université de Lille 2, 59000 Lille, France 
c Service de cardiologie, institut lorrain du cœur et des vaisseaux Louis-Mathieu, 54500 Vandoeuvre-lès-Nancy, France 
d Service de cardiologie, hôpital Saint-Antoine, université Pierre-et-Marie-Curie, Assistance publique–Hôpitaux de Paris, 75012 Paris, France 
e Service de cardiologie, GRC Amyloid Research Institute and Mondor Amyloidosis Network, DHU A-TVB, UPEC, hôpital Henri-Mondor, université Paris Est Créteil, Assistance publique–Hôpitaux de Paris, 94010 Paris, France 

Corresponding author at: service de cardiologie, pôle cardiovasculaire et pulmonaire, institut cœur-poumon, boulevard Prof.-J.-Leclercq, CHRU de Lille, 59037 Lille cedex, France.

Keywords : Guidelines, Heart failure, Treatment

Mots clés : Recommandations, Insuffisance cardiaque, Traitement

Abbreviations : ACC, ACEI, AHA, ARB, ARNI, BNP, ESC, HF, HFmrEF, HFpEF, HFrEF, HFSA, ICD, LBBB, LVEF, MRA, NP, NT-proBNP, NYHA


Background

Despite a significant improvement in therapeutic management, heart failure (HF) remains a major health problem. In France, recent publications clearly show that mortality and rehospitalization rates for HF remain high [1, 2, 3, 4].

The new European Society of Cardiology (ESC) guidelines for the management of patients with HF were presented and published in May 2016 [5]. Concomitantly, an update of the 2013 American College of Cardiology (ACC) Foundation/American Heart Association (AHA) guidelines [6], focused on the pharmacological treatment, was published by the ACC/AHA/Heart Failure Society of America (HFSA) [7]. We are obliged to follow these guidelines as closely as possible. However, as always, some statements raise questions. We will comment on some of these, focusing on the change in HF definition, diagnostic algorithm, and preventive and curative treatments in patients with chronic HF.

As always, guidelines are based on classes of recommendations (class I: recommended; IIa: should be considered; IIB: may be considered; III: not recommended) and level of evidence (A: multiple randomized studies or meta-analyses; B: single randomized study or large non-randomized studies; C: expert opinion or small, retrospective studies or registries) [5].

A new classification of chronic heart failure

The most important parameter used to classify HF is left ventricular ejection fraction (LVEF). Previous 2012 ESC guidelines [8] used the threshold of 50% for LVEF to divide patients with HF into two groups: those with a LVEF50% had HF with reduced ejection fraction (HFrEF) while those with LVEF>50% were classified as HF with preserved ejection fraction (HFpEF) (Table 1). Most of the major HFrEF clinical trials included patients with LVEF35%. Therefore, the subgroup of HFrEF patients with LVEF 36–50% were individualized as patients with mild systolic dysfunction without clear therapeutic recommendations. In clinical practice, most of these patients received the same treatment as patients with LVEF35%. The new ESC guidelines [5] propose a new subgroup of HF, namely HF with mid-range ejection fraction (HFmrEF), defined as LVEF 40–49% (Table 1). Consequently, the two other subgroups are HFpEF when LVEF50% and HFrEF when LVEF<40%. Patients with either HFmrEF or HFpEF must have structural cardiac abnormalities (left ventricular hypertrophy, left atrial dilatation or diastolic dysfunction) and an increase in natriuretic peptides (NPs). Echocardiography plays a key role in patients with HF, depending on the mode of presentation, for diagnosis, aetiology determination, treatment planning and follow-up. Appropriateness criteria have been reported and compared to available guidelines, highlighting difficulties or uncertainties in clinical practice [9]. This new classification has the advantage of clearly defining different cut-off values of LVEF for HFpEF (≥50%) and for the “grey zone”, HFmrEF. This classification will also stimulate new research into the pathophysiology and treatment of HFmrEF and HFpEF.

In clinical practice, there are several limitations to the use of this new definition. First is the measurement of LVEF itself, although this limitation is true for all LVEF cut-off values. LVEF measurement is subject to high inter- and intra-observer variability when using one technique, but also varies when different techniques are used to measure it (echocardiography, radionuclide angiography and magnetic resonance imaging). In clinical practice, the method of choice is echocardiography, and most cardiologists generally determine LVEF by a combination of different methods (visual estimation, four-cavity Simpson method or biplane method) and consequently, use increments of 5% (i.e. 30%, 35%, 40%, 45%) [10]. Second, most HFrEF treatments are indicated for patients with LVEF35%. Therefore, this new definition creates a subgroup of HFrEF with LVEF 36–39% without clear recommended treatments. Third, patients in the five major clinical trials in HFpEF (DIG [11], PEP-CHF [12], CHARM-Preserved [13], I-PRESERVE [14], TOPCAT [15]) had LVEF>40%. Thus, why are patients only considered to have HFpEF when their LVEF is50%? Finally, patients with LVEF of 40% are now classified as HFmrEF and not HFrEF patients, contrasting with USA guidelines [6] (Table 1).

Guidelines are lacking for patients with an initial reduced LVEF (≤40%) who had a significant LVEF increase (LVEF>40%) after appropriate treatment (either medications or resynchronization therapy). Should they be included in the HFmrEF or HFpEF subgroups? Recent publications show that recovered HF patients do not have the same clinical presentation as HFpEF patients and do not have the same prognosis as those who do not recover [16, 17]. In contrast with ESC guidelines, such patients have been individualized in USA guidelines as “patients with recovered EF” or “improved HFpEF” [6] (Table 1). As for HFmrEF, we need to improve our knowledge of the pathophysiology and treatment of this subgroup of patients.

Diagnostic algorithm in chronic heart failure

In patients with chronic (i.e. not acute) HF, a clear algorithm is presented in the new ESC guidelines [5]. This algorithm is firstly based on clinical history, signs and symptoms, and electrocardiogram findings. NP measurement and/or echocardiography is to be performed after this first step rather than immediately in patients with symptoms. Compared with the 2012 version of the ESC guidelines [8], we do appreciate that the clinical evaluation has been integrated. In most cases, general practitioners are the first contact of the patient. Although HF is unlikely in a patient with a normal electrocardiogram, its interest is limited in France because few general practitioners performed electrocardiograms. The diagnostic algorithm recommends that all patients with symptoms suggestive of HF should be seen by a cardiologist, but this is not realistic in clinical practice. However, this algorithm is appropriate to be able to exclude HF in symptomatic patients. HF is also unlikely in patients with low NP levels, but the thresholds for NP (which are similar to those presented in the 2012 ESC guidelines [8]), appear to be surprisingly low (≥35pg/mL for B-type natriuretic peptide [BNP] or125pg/mL for N-terminal pro-B type natriuretic peptide [NT-proBNP] [5]), particularly for HFpEF, with mainly affects elderly patients. In contrast, echocardiography should be performed in patients with increased NP levels to confirm the presence of cardiac structural abnormalities. Echocardiography should also be performed when NP determination is not available. Finally, in France, HF is likely to be diagnosed after clinical evaluation and NP measurement, but before evaluation by a cardiologist.

Diagnostic tests are only recommended if their results imply “a meaningful clinical consequence” [5]. Echocardiography remains the technique of choice for the diagnosis and management of patients with HF (level of recommendation: I – C). However, new techniques have been added to the new ESC guidelines [5]: tissue Doppler imaging and strain (IIa – C), cardiac magnetic resonance imaging with late gadolinium enhancement (IIa – C), cardiac computed tomography for the analysis of coronary arteries (IIb – C) and bone scintigraphy (3,3-diphosphono-1,2-propanodicarboxylicacid) for the diagnosis of transthyretin cardiac amyloidosis (no level of recommendation), an underestimated cause of heart failure [18, 19, 20]. The level of recommendation has been changed for non-invasive stress imaging, from IIa – C [8] to IIb – B [5].

Delay or prevention of chronic heart failure

A new chapter has been included in the new ESC guidelines [8], focused on delaying or preventing clinical HF. The authors summarize important recommendations for the management of hypertension, dyslipidaemia, control of other cardiac risk factors with counselling and drugs (e.g. angiotensin converting enzyme inhibitors [ACEIs], beta-blockers) (levels of recommendation from I – A to IIa – C), but also empagliflozin for patients with diabetes mellitus (IIa – B) [21].

Treatment of chronic heart failure

The most keenly awaited chapter was the one detailing the recommendations on the treatment of chronic HF. The cornerstone of the treatment of left ventricular systolic dysfunction remains the combination of ACEI and beta-blockers, up-titrated to maximal tolerated doses (I – A) [5]. Mineralocorticoid receptor antagonists (MRAs) are recommended for symptomatic patients with LVEF35% and either a recent hospitalization for HF (<6 months) or elevated NP (BNP>250pg/mL or NT-proBNP>500pg/mL in men or>750pg/mL in women) (I – A). The up-titration to maximal tolerated doses is an extremely important step that will have a significant impact on the second step. If the position of MRA in the chart cannot be discussed in general, we must keep in mind that the mean age of French patients with HF is close to 80 years. In elderly patients, it might be dangerous to choose this option systematically due to the risk of renal failure and/or hyperkalemia.

Three options are available for patients who remain symptomatic with LVEF35% [5]. In case of QRS130ms, cardiac resynchronization therapy (CRT) must be considered (the various levels of recommendation are shown in Table 2). If the heart rate is70 bpm and the patient is in sinus rhythm, ivabradine should be added (IIa – B). If the patient is tolerant to ACEI (or angiotensin receptor blockers [ARBs]) at maximal dosage (i.e. “doses equivalent to enalapril 10mg b.i.d.” [5]) but still have increased NP levels (BNP150pg/mL or NT-proBNP600pg/mL or, in case of HF hospitalization within 12 months, BNP100pg/mL or NT-proBNP400pg/mL), the replacement of these drugs by an angiotensin receptor neprilysin inhibitor (ARNI), namely LCZ696 (valsartan/sacubitril), must be considered (I – B). This switch requires the ACEI to be stopped 36hours before starting the ARNI due to the potential risk of angioedema. This recommendation follows the results of the PARADIGM-HF trial [22], which demonstrated, for the first time since the SOLVD trial [23], that a new drug, LCZ696, significantly reduced total mortality compared with enalapril, an ACEI.

Other recommendations are not new, but have been updated [5]. For example, diuretic treatment is always required at minimal doses to control water and sodium retention, but with a new level of recommendation (I – B), based only on results of meta-analyses. The level of recommendation for ARB use has been decreased without any new data. The level of recommendation of ARB as an alternative in patients with ACEI intolerance has been changed (I – A in 2012 [8] to I – B in 2016 [5]) and the combination of ACEI and ARB is only recommended in patients who are intolerant to MRA (I – A to IIb – C). Renin inhibitors are not recommended as an alternative to ACEI/ARB. Initiation of statins is not recommended, but statins must be prescribed in ischaemic heart disease.

The new treatment algorithm seems clear at first glance. However, it raises some questions and comments.

Is the recommendation for ARNI too restrictive for clinical practice?

The ESC guidelines for ARNI strictly follow the inclusion criteria of PARADIGM-HF [22], particularly the need to tolerate the 10mg twice daily dose-equivalent of enalapril. In clinical practice, not all patients reach the maximal dosage of ACEI/ARB due to hypotension or renal failure. Strictly following the ESC guidelines, these patients should not receive ARNI. In contrast, updated USA guidelines recommend the switch from ACEI/ARB to LCZ696 in patients with HFrEF (LVEF40%) and when the maximal tolerated dose of ACEI/ARB is obtained (I – B) [7], allowing the potential prescription of ARNI in a larger number of patients than with the ESC guidelines [5]. Even with these limitations, ARNI could potentially be prescribed in a great number of patients with HF. Finally, the long-term safety of ARNI needs to be addressed, particularly the real-life risk of angioedema [24].

When patients remain symptomatic with maximal tolerated doses of ACEI/ARB and beta-blockers, which of these three options must be considered first and/or in combination: CRT, LCZ696, ivabradine?

The 2016 ESC guidelines [5] mention that “These above treatments may be combined if indicated”. However, the question is, in which sequence? CRT first, then ivabradine, then LCZ696; or ivabradine then LCZ696 and, finally, CRT?

Our main objective as clinicians is to improve the prognosis of our patients with HF. Optimization of the treatment must be individualized, based on risk stratification. The levels of recommendation are different for these proposals, and that could be one of the arguments to help us decode (LCZ696: I; ivabradine: IIa; CRT: I or IIa, depending on the width and the morphology of QRS). LCZ696 and CRT have been reported to reduce all-cause mortality [22, 25]; in contrast, ivabradine has no significant impact on total mortality [26]. The improvement of LVEF is greater with CRT (+5%) than with ivabradine (+2%) [27, 28]; and we do not currently have any information on left ventricular remodelling with LCZ696.

We can suggest that in patients with left bundle branch block (LBBB) (QRS150ms), CRT should be the first treatment of choice, while in patients with a heart rate75 bpm despite maximal doses of beta-blockers, ivabradine seems to be a good option. In other cases, LCZ696 should replace ACEI/ARB and if patients do not reach the therapeutic goals (New York Heart Association [NYHA] class>I, LVEF35%, heart rate70 bpm, elevated NP), treatment tailoring is required.

Cardiac resynchronization therapy recommendations

The other important modifications between the 2012 [8] and the 2016 ESC guidelines [5] concern CRT. In 2012, CRT was recommended for patients in sinus rhythm with a LVEF30% in two situations:

LBBB morphology with a QRS130ms for those in NYHA class II and QRS120ms for those in NYHA class III (I – A);
non-LBBB morphology with QRS150ms (IIa – A).

In 2016 [5], the level of LVEF and the width of QRS have changed following the publication of the EchoCRT study [29]. New recommendations regarding CRT are summarized in Table 2.

There is uncertainty in patients with atrial fibrillation, and atrioventricular nodal ablation is recommended only in patients with a high ventricular rate (>110 bpm) despite optimal medical therapy. CRT is indicated – rather than right ventricular pacing – in symptomatic patients with HFrEF, regardless of NYHA class, who have an indication for ventricular pacing and high-degree atrioventricular block to reduce morbidity whatever their rhythm (sinus or atrial fibrillation). In these two scenarios, ventricular capture needs to be>98%.

For implantable cardioverter-defibrillators (ICDs), there is no significant modification. An ICD is recommended if LVEF is35% despite optimal medical therapy (for 3 months) (I – A in patients with ischaemic heart disease; I – B in those with other cardiac diseases) or in secondary prevention (I – A). However, for primary prevention in patients with dilated cardiomyopathy, recommendations will probably be changed following the publication of the DANISH trial, which demonstrated no reduction in total mortality with ICDs [30]. Finally, wearable ICDs may be considered to reduce the risk of sudden cardiac death for a limited period or as a bridge to an implanted device (IIb – C) and subcutaneous ICDs are also an alternative option.

As in the 2012 guidelines [8], there is a chapter dedicated to the importance of non-pharmacological non-device/surgical interventions used in the management of HF patients [5]. Regular exercise and a multidisciplinary care management programme are strongly recommended (I – A). Telemonitoring (CardioMems, ICD) appears in these recommendations with a level of recommendation of IIB – B. Interventions to improve medication adherence among patients with HF have significant effects on reducing readmissions and decreasing mortality [31].

Co-morbidities

Co-morbidities are presented in alphabetical order and anaemia has been integrated in the section on iron deficiency [5]. Based on the results of different randomized trials, intravenous ferric carboxymaltose should be considered (IIa – A) in patients with iron deficiency to improve symptoms, exercise capacity and quality of life [32, 33]. Following the results of the RED-HF trial with darbepoetin [34], erythropoietin-stimulating agents are not recommended for the treatment of anaemia.

Similarly, due to the negative results of the SERVE-HF trial [35], which showed a significant increase in mortality in the treatment arm, adaptive servo-ventilation is contraindicated in patients with predominant central sleep apnoea and HFrEF (III – B). However, there is no recommendation concerning the alternative methods to treat central sleep apnoea or in patients with HFmrEF or HFpEF. For obstructive sleep apnoea, all treatment methods should be considered in case of apnoea-hypopnea index>30/h, but no trial has studied the impact of these methods on survival.

Limitations

We have not discussed several important topics (acute heart failure, management of atrial fibrillation, valvular diseases or myocardial ischaemia). We aimed to focus on the most important changes and share our personal point of view, mostly on how the ESC guidelines could be interpreted in clinical practice. Guidelines are based on scientific level of evidence (clinical trials) and it is difficult to recommend anything rational when the proof is lacking.

Conclusions

We now have the responsibility of following the new ESC guidelines and to share the information with all cardiologists to improve the management of patients with chronic systolic heart failure. The road is long, but we have the best guide to avoid getting lost!

Sources of funding

None.

Disclosure of interest

P. de G. Received consultant fees from Actelion, Bayer, MSD, Novartis, Sanofi-Aventis, Servier, Resmed, Vifor Pharma for participating in advisory boards and from Actelion, Bayer, Novartis, Servier Vifor for participation in meetings as speaker or chairman.

A. C. Received a research grant for research nurses (RESICARD) and consultant and lecture fees from Astra-Zeneca, Bayer Pharma, BMS, Boehringer-Ingelheim, Daiichi Sankyo, Novartis.

Y. J. Received honoraria from Bayer, Boston Scientific, Servier, Saint-Jude Medical, Novartis for participating in advisory boards, and from Abbott Vascular, Amgen, Astra-Zeneca, Bristol-Myers-Squibb, Boston Scientific, GSK, Medicines Company, MSD-Schering-Plough, Novartis, Roche Diagnostics, Sanofi-Aventis, Saint-Jude Medical for participation in investigational trials as French national coordinator and/or meetings as speaker or chairman.

T. D. Received honoraria, meeting, research grants from Alnylam, Actelion, Astra-Zeneca, Bayer, GSK, Menarini, Novartis, Pfizer, Resmed, Servier, Thorax-St Jude Medica, Vifor Pharma.

References

Tuppin P., Cuerq A., de Peretti C., and al. First hospitalization for heart failure in France in 2009: patient characteristics and 30-day follow-up Arch Cardiovasc Dis 2013 ;  106 : 570-585 [inter-ref]
Juilliere Y., Suty-Selton C., Riant E., and al. Prescription of cardiovascular drugs in the French ODIN cohort of heart failure patients according to age and type of chronic heart failure Arch Cardiovasc Dis 2014 ;  107 : 21-32 [cross-ref]
Tuppin P., Cuerq A., de Peretti C., and al. Two-year outcome of patients after a first hospitalization for heart failure: a national observational study Arch Cardiovasc Dis 2014 ;  107 : 158-168 [inter-ref]
Tuppin P., Riviere S., Rigault A., and al. Prevalence and economic burden of cardiovascular diseases in France in 2013 according to the national health insurance scheme database Arch Cardiovasc Dis 2016 ;  109 : 399-411 [inter-ref]
Ponikowski P., Voors A.A., Anker S.D., and al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC Eur Heart J 2016 ;  37 : 2129-2200 [cross-ref]
Yancy C.W., Jessup M., Bozkurt B., and al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines J Am Coll Cardiol 2013 ;  62 : e147-e239
Yancy C.W., Jessup M., Bozkurt B., and al. 2016 ACC/AHA/HFSA focused update on new pharmacological therapy for heart failure: an update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America J Am Coll Cardiol 2016 ;  68 : 1476-1488 [cross-ref]
McMurray J.J., Adamopoulos S., Anker S.D., and al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC Eur Heart J 2012 ;  33 : 1787-1847
Garbi M., Edvardsen T., Bax J., and al. EACVI appropriateness criteria for the use of cardiovascular imaging in heart failure derived from European National Imaging Societies voting Eur Heart J Cardiovasc Imaging 2016 ;  17 : 711-721 [cross-ref]
Cikes M., Solomon S.D. Beyond ejection fraction: an integrative approach for assessment of cardiac structure and function in heart failure Eur Heart J 2016 ;  37 : 1642-1650 [cross-ref]
Ahmed A., Rich M.W., Fleg J.L., and al. Effects of digoxin on morbidity and mortality in diastolic heart failure: the ancillary digitalis investigation group trial Circulation 2006 ;  114 : 397-403 [cross-ref]
Cleland J.G., Tendera M., Adamus J., Freemantle N., Polonski L., Taylor J. The perindopril in elderly people with chronic heart failure (PEP-CHF) study Eur Heart J 2006 ;  27 : 2338-2345 [cross-ref]
Yusuf S., Pfeffer M.A., Swedberg K., and al. Effects of candesartan in patients with chronic heart failure and preserved left ventricular ejection fraction: the CHARM-Preserved Trial Lancet 2003 ;  362 : 777-781 [cross-ref]
Massie B.M., Carson P.E., McMurray J.J., and al. Irbesartan in patients with heart failure and preserved ejection fraction N Engl J Med 2008 ;  359 : 2456-2467 [cross-ref]
Pitt B., Pfeffer M.A., Assmann S.F., and al. Spironolactone for heart failure with preserved ejection fraction N Engl J Med 2014 ;  370 : 1383-1392 [cross-ref]
Punnoose L.R., Givertz M.M., Lewis E.F., Pratibhu P., Stevenson L.W., Desai A.S. Heart failure with recovered ejection fraction: a distinct clinical entity J Card Fail 2011 ;  17 : 527-532 [cross-ref]
de Groote P., Fertin M., Duva Pentiah A., Goeminne C., Lamblin N., Bauters C. Long-term functional and clinical follow-up of patients with heart failure with recovered left ventricular ejection fraction after beta-blocker therapy Circ Heart Fail 2014 ;  7 : 434-439 [cross-ref]
Gillmore J.D., Maurer M.S., Falk R.H., and al. Nonbiopsy diagnosis of cardiac transthyretin amyloidosis Circulation 2016 ;  133 : 2404-2412 [cross-ref]
Galat A., Rosso J., Guellich A., and al. Usefulness of (99m)Tc-HMDP scintigraphy for the etiologic diagnosis and prognosis of cardiac amyloidosis Amyloid 2015 ;  22 : 210-220 [cross-ref]
Damy T., Costes B., Hagege A.A., and al. Prevalence and clinical phenotype of hereditary transthyretin amyloid cardiomyopathy in patients with increased left ventricular wall thickness Eur Heart J 2016 ;  37 : 1826-1834 [cross-ref]
Zinman B., Wanner C., Lachin J.M., and al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes N Engl J Med 2015 ;  373 : 2117-2128 [cross-ref]
McMurray J.J., Packer M., Desai A.S., and al. Angiotensin-neprilysin inhibition versus enalapril in heart failure N Engl J Med 2014 ;  371 : 993-1004 [cross-ref]
The SOLVD Investigators Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure N Engl J Med 1991 ;  325 : 293-302
Juilliere Y., Ferrieres J. [New therapeutic era in heart failure with reduced ejection fraction: which population of French patients is concerned?] Ann Cardiol Angeiol (Paris) 2016 ;  65 : 237-239 [cross-ref]
Tang A.S., Wells G.A., Talajic M., and al. Cardiac resynchronization therapy for mild-to-moderate heart failure N Engl J Med 2010 ;  363 : 2385-2395 [cross-ref]
Swedberg K., Komajda M., Bohm M., and al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study Lancet 2010 ;  376 : 875-885 [cross-ref]
Tardif J.C., O’Meara E., Komajda M., and al. Effects of selective heart rate reduction with ivabradine on left ventricular remodelling and function: results from the SHIFT echocardiography substudy Eur Heart J 2011 ;  32 : 2507-2515 [cross-ref]
Solomon S.D., Foster E., Bourgoun M., and al. Effect of cardiac resynchronization therapy on reverse remodeling and relation to outcome: multicenter automatic defibrillator implantation trial: cardiac resynchronization therapy Circulation 2010 ;  122 : 985-992 [cross-ref]
Ruschitzka F., Abraham W.T., Singh J.P., and al. Cardiac resynchronization therapy in heart failure with a narrow QRS complex N Engl J Med 2013 ;  369 : 1395-1405 [cross-ref]
Kober L., Thune J.J., Nielsen J.C., and al. Defibrillator implantation in patients with nonischemic systolic heart failure N Engl J Med 2016 ;  375 : 1221-1230 [cross-ref]
Ruppar T.M., Cooper P.S., Mehr D.R., Delgado J.M., Dunbar-Jacob J.M. Medication adherence interventions improve heart failure mortality and readmission rates: systematic review and meta-analysis of controlled trials J Am Heart Assoc 2016 ;  5 :
Anker S.D., Comin-Colet J., Filippatos G., and al. Ferric carboxymaltose in patients with heart failure and iron deficiency N Engl J Med 2009 ;  361 : 2436-2448 [cross-ref]
Ponikowski P., van Veldhuisen D.J., Comin-Colet J., and al. Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency dagger Eur Heart J 2015 ;  36 : 657-668 [cross-ref]
Swedberg K., Young J.B., Anand I.S., and al. Treatment of anemia with darbepoetin alfa in systolic heart failure N Engl J Med 2013 ;  368 : 1210-1219 [cross-ref]
Cowie M.R., Woehrle H., Wegscheider K., and al. Adaptive servo-ventilation for central sleep apnea in systolic heart failure N Engl J Med 2015 ;  373 : 1095-1105 [cross-ref]



© 2016  Elsevier Masson SAS. All Rights Reserved.
EM-CONSULTE.COM is registrered at the CNIL, déclaration n° 1286925.
As per the Law relating to information storage and personal integrity, you have the right to oppose (art 26 of that law), access (art 34 of that law) and rectify (art 36 of that law) your personal data. You may thus request that your data, should it be inaccurate, incomplete, unclear, outdated, not be used or stored, be corrected, clarified, updated or deleted.
Personal information regarding our website's visitors, including their identity, is confidential.
The owners of this website hereby guarantee to respect the legal confidentiality conditions, applicable in France, and not to disclose this data to third parties.
Close
Article Outline