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Highlights from the new ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure (version 2012)

The new ESC Guidelines for the diagnosis and treatment of heart failure (HF) have been released four years after the former ones. Four plentiful years of considerable scientific evidence in HF field. They were presented in May 2012 at the Heart Failure Congress 2012 and afterwards published in the European Heart Journal (1).

Heart Failure (HF)


The most important changes relate to:

1.Classification

The classification of HF by structural abnormality (ACC/AHA: from stage A to D) is no more considered; the one considered is the New York Heart Association (NYHA: from class I to IV) based on severity of symptoms and physical activity.

2.Co-morbidities

Management of co-morbidities is fundamental for the holistic care of patients with HF. The new co-morbidities considered are:

  • Angina pectoris: on the contrary of beta-blockers, diltiazem and verapamil are considered unsafe in
    HF-REF(reduced ejection fraction). Percutaneous and surgical revascularization can be alternative approaches to the treatment of angina.
  • Cancer: some chemotherapeutic agents, such as trastuzumab and anthracyclines, can cause or aggravate left ventricle (LV) dysfunction and HF. Pre-  and post-evaluation of EF is essential in patients receiving cardiotoxic chemotheraphy. Dexarazoxane may confer cardioprotection versus anthracyclines.
  • Depression: it worsens clinical status and prognosis in HF. Selective serotonin reuptake inhibitors are thought to be safe; on the contrary tryciclic antidepressant are not.
  • Erectile dysfunction: phosphodiesterase inhibitor can be useful in HF patients unless they are taking nitrates or have hypertrophic cardiomyopathy.
  • Prostatic dysfunction: alpha-adrenoceptor blockers may not be safe in HF because they cause hypotension, sodium and water retention. 5-alpha reductase inhibitors are preferred.
  • Hypertension: negatively inotropic calcium channel blockers (CCbs) and moxonidine are contraindicated in patients with HF-REF. Angiotensin converting enzyme inhibitors (ACE-I), angiotensin receptor blockers (ARBs), beta-blockers (BBs), mineral corticoid receptor antagonists (MRAs), diuretics, hydralazine, and amlodipine (or felodipine) are suggested in chronic hypertension. Nitrates i. v. or sodium nitroprusside are recommended to lower blood pressure.
  • Holistic management: regular aerobic exercise is recommended in patients with HF to improve functional capacity and symptoms (class I, level A). It is recommended that patients with HF are enrolled in a multidisciplinary-care management programme to reduce the risk of HF hospitalization (class I, level A).
  • Acute HF: after stabilization it is suggested to go on ACE-I/ARBs, BBs, MRAs and digoxin. The dose should be up-titrated as far as possible before discharge, and a plan made to complete dose up-titration after discharge.

3.Diagnostic procedures

a) BNP and NT-proBNP: for patients presenting with acute onset or worsening of symptoms the cut-off points for optimal exclusion are respectively 100 and 300 pg/mL; for chronic patients they are 35 and 125 pg/mL. In this case the sensitivity and specificity for the diagnosis of HF is lower. Natriuretic peptides can also be used to obtain prognostic information (Class IIa, level C). 

b) MRproANP: a new marker to be used in acute setting with a cut-off point of 120 pmol/L. 

c) New laboratory tests: thyrotropin, blood glucose to identify undiagnosed diabetes and liver enzymes.

d) Chest X-ray is of limited use in the diagnostic work-up. Significant LV systolic dysfunction may be present without cardiomegaly on the chest X-ray.

e) Echocardiography maintains a fundamental role for evaluation of cardiac anatomy and function. Three-dimensional echocardiography improves quantification of ventricular volume and ejection fraction calculation (I-C recommendation).

f) Cardiac magnetic resonance is particularly valuable in identifying and stratifying inflammatory and infiltrative conditions. It has limited availability and quality is limited in arrhythmias. Linear gadolineum chelates are contraindicated in subjects with a GFR < 30 mL/min/m2.

4.Therapeutic recommendations

The guidelines state the treatment effect supported by the class and level of recommendation in tabular format and also focus, sometimes, on mortality and morbidity outcome.

A/ Pharmacological treatment 

a) A new indication for the sinus node inhibitor ivabradine

According to the SHIFT study, ivabradine can be considered to reduce the risk of heart failure hospitalization in patients in sinus rhythm with an ejection fraction =35%, a heart rate remaining =70 bpm, and persisting symptoms (NYHA Class II-IV) despite optimal treatment with an evidence-based dose of BBs, ACE-I (or ARBs if not tolerated) and a MRA (Class IIa, level). Ivabradine also improves LV function and quality of life.

b) An expansion of the indication for mineralo-corticoid (aldosterone) receptor antagonists

MRAs such as spironolactone or eplerenone (according to EPHESUS and EMPHASIS-HF) are now recommended for all heart failure symptomatic patients (NYHA Class II-IV) and an ejection fraction =35% despite treatment with an ACE-I and a BB to reduce the risk of heart failure hospitalization and the risk of premature death (class I, level A). Reductions were also seen in rates of death for any cause (24%), hospitalization for any reason (23%) and cardiovascular death (24 %).

c) Angiotensin receptor blockers

Recommended to reduce the risk of HF hospitalization and the risk of premature death in patients with EF < 40% intolerant of an ACE-I (Class I, level A) or may be added to ACE-I and BBs in patients with EF <40% and NYHA II-VI unable to tolerate MRA (Class I, level A).

No treatment has yet been shown to reduce mortality and morbidity in patients with HF with preserved ejection fraction (HFPEF) unless two very small studies have shown that verapamil (CCB of the phenylalkylamine class) may improve exercise capacity and symptoms. BBs may be used to reduce heart rate in patients with HFPEF and atrial fibrillation.

B/ Non surgical device treatment in HFREF patients

a) An expanded indication for cardiac resynchronisation therapy (CRT)

CRT (preferably CRT-defibrillator: CRT-D) is now recommended in NYHA class II heart failure patients as well as in those who are more severely symptomatic despite optimal pharmacological therapy. CRT-Pacemaker or CRT-D  is indicated if the patients are in sinus rhythm with a QRS duration of =130 ms, LBBB QRS morphology,  and an ejection fraction =30% and if expected to survive with good functional status for more than one year, to reduce the risk of heart failure hospitalization and the risk of premature death (Class I, level A). In contrast, in patients who do not have a LBBB QRS morphology, a QRS duration of =150 ms is required (Class IIa, level A). The guideline also indicates that the evidence for CRT is uncertain in two commonly encountered clinical situations, in patients with atrial fibrillation and when a patient with a reduced ejection fraction has an indication for conventional pacing and no other indication for CRT.

b) Recognition of the growing use of ventricular assist devices

Left ventricular or biventricular assist devices (LVAD or BIVAD) are recommended in selected patients with systolic heart failure at end stage heart failure despite optimal pharmacological and device treatment and who are otherwise suitable for heart transplantation to improve symptoms and reduce the risk of heart failure hospitalization for worsening of HF and to reduce the risk of premature death while awaiting transplantation (Class I level B). A LVAD could also be recommended in patients with the same traits and aims, but not suitable for heart transplantation and expected to survive > 1 year with good functional status (Class IIa level B). However all these patients are required to have severe heart failure symptoms for more than two months despite optimal medical and device therapy and more than one of the following conditions: LVEF < 25% and VO2 peak < 12 mL/Kg/min; =3 HF hospitalization in previous 12 months without an obvious precipitating cause; dependence on i.v. inotropic therapy; progressive end–organ dysfunction due to reduced perfusion and not to inadequate ventricular filling pressure; deterioration of right ventricular function.

c) The emergence of transcatheter valve interventions

Valvular heart disease may be the underlying aetiology for HF or an important aggravating factor. Low-dose dobutamine stress echocardiography is recommended to differentiate between severe aortic stenosis and pseudo-aortic stenosis and also to provide information about myocardial contractile reserve which is of prognostic importance. Transcatheter aortic valve replacement should be considered in patients with heart failure and severe aortic stenosis if patients are not medically fit for surgery. The differentiation between primary and secondary mitral regurgitation is crucial. Secondary regurgitation occurs because left ventricle enlargement and remodeling lead to reduced leaflet closing. It can be prevented and reduced by an effective medical therapy. In patients with secondary mitral regurgitation and judged inoperable or at unacceptably high surgical risk, percutaneous edge-to-edge repair (mitral clip) may be considered in order to improve symptoms. In presence of atrial fibrillation atrial ablation and left atrial appendage closure may be considered at the time of mitral valve surgery.

C/ New information on the role of coronary revascularization in HF

Surgical coronary revascularization (CABG) is recommended for relief of angina in patients with significant left main stenosis, suitable for surgery and expected to survive > 1 year with good functional status, to reduce the risk of premature death (Class I, level C).

CABG is also recommended in case of two-or three vessel coronary disease including a left anterior descending stenosis to reduce the risk of hospitalization for cardiovascular causes and the risk of premature death from cardiovascular causes (Class I level B).

In the above categories PCI may be considered as an alternative to CABG when the patients are unsuitable for surgery (Class IIb, level C). The benefit-risk balance for CABG and PCI in patients without angina/ischemia or without viable myocardium remains uncertain and are not recommended (Class III,  level C). The choice of PCI or CABG is based on the extent of CAD, expected completeness of revascularization, associated valvular disease and presence of co-morbidities.

Conclusion
In conclusion these new guidelines are very concise and aim to assist clinical physicians in adopting the best strategies for patient with heart failure. The wealth of evidence let the recommendations on chronic heart failure resulting from left ventricular systolic dysfunction focus on mortality and morbidity outcomes. They consider the impact on outcome and risk–benefit ratio of diagnostic and therapeutic procedures. Other relevant guidelines, consensus statements, and position papers are cited to avoid a very long text. We know that the implementation of these guidelines depends on individual patients as well as on socio-economic factors and European national health services rules. The ESC and the Council for Cardiology Practice together with National cardiological societies will give their useful contribution to implement them in clinical practi