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The key points from the European Society of Cardiology (ESC) Guide
for the Diagnosis and Treatment of Acute and Chronic Heart Failure (HF)
from 2021 [1] are presented, as well as some views from the American
ACC / AHA Guidelines from 2022 [2]:
Heart failure (HF) nomenclature with left ventricular ejection
fraction (LVEF) of 41-49% has been revised in HF with mildly reduced
EF (HFmEF). HF with LVEF ≤40% remains HF with reduced EF (HFrEF),
and HF with LVEF ≥50% remains HF with preserved EF (HFpEF).
Table 1. Heart failure (HF) nomenclature from ESC guideline 2021
All patients with suspected HF should have: electrocardiogram,
transthoracic echocardiogram, X-ray of thorax (lung and heart),
complete blood count, urea, creatinine, electrolytes, thyroid
hormones, glycosylated hemoglobin (HbA1c), lipid status, iron
analysis, peptide (BNP / NT-proBNP). Magnetic resonance imaging of
the heart is recommended in patients with poor acoustic window for
ultrasound of the heart or in patients with suspected infiltrative
cardiomyopathy, amyloidosis , hemochromatosis, dilated
non-compaction cardiomyopathy or myocarditis [1]. The new diagnostic
algorithm for heart failure (HF) is shown in Figure 1.
FIGURE 1. DIAGNOSTIC ALGORITHM FOR HEART
INSUFFICIENCY (HF) ACCORDING TO THE NEW ESC GUIDE 2021.
LEGEND: Heart failure with reduced left ventricular ejection
fraction (HFrEF)
Heart failure with mildly reduced left ventricular ejection fraction
(HFmrEF)
Heart failure with preserved left ventricular ejection fraction (HFpEF)
Available at www.escardio.org/guidelines (doi: 10.1093/eurheartj/ehab368)
Medical, primarily drug therapy directed by the New ESC Guide,
ie guidelines for patients with heart failure (HF) with reduced
ejection fraction (HFrEF) brings significant innovations and changes
in the treatment paradigm, from the gradual introduction of drugs to
the simultaneous introduction of 5 main classes of drugs.
Treatment of heart failure with reduced left ventricular ejection
fraction (HFrEF) and symptoms of class II-New York Heart Association
(NYHA) -dispnea at higher exertion and higher classes, now includes
angiotensin receptor inhibitor neprilysin (ARNI) as a substitute for
angiotenzin convertase enzyme inhibitor( ACEI). Another significant
innovation is the addition of SGLT-2 (Sodium Glucose channels
Cotransporter-2) inhibitors, dapagliflozin or empagliflozin in
first-line therapy for heart failure, simultaneously with the
introduction of beta-blockers, ACEI or ARNI, mineralocorticoid
receptor inhibitors and diuretics. class I. (picture 2)
Figure 2. Treatment of patients with HEART
INSUFFICIENCY WITH REDUCED EJECTION FRAGMENT (HFrEF) according to
the ESC guide from 2021
Legend ACE-I = angiotensin converting enzyme
inhibitor; ARNI = angiotensin receptor-neprilysin inhibitor; ARB =
angiotensin receptor blocker; BB = beta-blocker; CRT-D = pacemaker
for cardiac resynchronization with a defibrillator; CRT-P =
pacemaker for cardiac resynchronization; Available at
www.escardio.org/guidelines (doi: 10.1093/eurheartj/ehab368)
Excessive neurohumoral activation antagonists, beta-adrenergic
receptor blockers, and renin-angiotensin-aldosterone system
antagonists have shown a reduction in CV mortality in HFrEF in a
number of clinical randomized studies and have been the primary
therapy for heart failure for some time. These drugs achieved the
following beneficial effects: slowing the progression of left
ventricular remodeling, reducing discomfort, improving endurance and
quality of life in all symptomatic categories from NYHA class II to
NYHA class IV. Eplerenone as a selective mineralocorticoid
aldosterone receptor antagonist is recommended for NYHA class II,
while for severe class III-IV patients with beta-blockers and ACEIs
or sartans, a non-selective mineralocorticoid aldosterone receptor
antagonist beparon (beta blocker) should be added with . In
decompensated patients with severe congestion, Henle's loop
diuretics remain a pillar of therapy.
In the treatment of heart failure with reduced LVEF (HFrEF),
sacubitril-valsartan, a combined neprilysin and angiotensin
inhibitor (ARNI), was introduced in previous 2016 ESC guidelines,
which showed an additional reduction in CV mortality and
hospitalizations due to HFrEF compared to the ACE inhibitor enala .
Dapagliflozin and empagliflozin reduce the risk of cardiovascular
mortality or hospitalization due to HF in patients with HF and
reduced left ventricular ejection fraction <40% (HFrEF) [1] but
empagliflozin has also recently shown an effect in HFpEF [65%
ejection] .
In patients with HFrEF and NYHA class II to III symptoms, ARNi is
recommended to reduce morbidity and mortality (class 1A) [3-7].
In patients with previous or current symptoms of chronic HFrEF, the
use of ACEi is useful in reducing morbidity and mortality when ARNi
is not feasible (class 1A) [8-15].
In patients with previous or current symptoms of chronic HFrEF who
are intolerant to ACEi due to cough or angioedema and when the use
of ARNi is not feasible, the use of ARBs is recommended to reduce
morbidity and mortality [16-20].
In patients with previous or current symptoms of chronic HFrEF, in
whom the introduction of ARNi is not feasible, treatment with ACEi
or ARB gives high economic viability [2,21-27].
ARNi is contraindicated in concomitant ACEi or within 36 hours of
the last dose of ACEi, or in patients with a history of angioedema.
Recommendations for the administration of empagliflozin and
dapagliflozin that reduce cardiovascular mortality or
hospitalization due to HF in patients with HF and reduced left
ventricular ejection fraction <40% (HFrEF)
In patients with symptomatic chronic HFrEF, SGLT2i is recommended
to reduce hospitalization due to HF and cardiovascular mortality,
regardless of the presence of type 2 diabetes [28,29] and thus
introduced SGLT2i therapy has good economic justification [30,31].
Recommendations for HF with MILDLY reduced EF (HFmrEF)
In patients with HFmrEF, SGLT2i may be helpful in reducing
hospitalizations for HF and cardiovascular mortality [32]. Among
patients with current or previous symptomatic HFmrEF (LVEF, 41%
–49%), the use of ARNi, ACEi or ARB and MRA and evidence-based beta
blockers for HFrEF may be considered adequate for use to reduce the
risk of hospitalization for HF and cardiovascular mortality ,
especially among patients with LVEF at the lower end of this
spectrum [33-40].
Recommendations for HF with preserved EF (HFpEF) according to the
ACC / AHA guide from 2022 (ref 2)
- Patients with HFpEF and hypertension should be titrated with
antihypertensive drugs in order to achieve the target blood
pressure in accordance with published guidelines of clinical
practice for the prevention of morbidity [41-43].
- In patients with HFpEF, SGLT2 inhibitors may be useful in
reducing HF hospitalizations and cardiovascular mortality [44].
- In patients with HFpEF, treatment of atrial fibrillation
(AF) may be helpful in improving symptoms.
- In selected patients with HFpEF, mineralocorticoid receptor
(MRA) antagonists may be considered effective in reducing
hospitalizations, especially among patients with LVEF at the
lower end of this spectrum [45-47].
- In selected patients with HFpEF, the use of ARBs may be
considered to reduce hospitalizations, especially among patients
with LVEF at the lower end of this spectrum [48,49].
Implantable cardioverter-defibrillators (ICDs) are recommended
for the primary prevention of sudden cardiac death in symptomatic
ischemic or non-ischemic cardiomyopathy with LVEF ≤35% despite 3
months of optimal targeted therapy (GDMT) if 1-year survival is
expected. ICD is not recommended within 40 days of myocardial
infarction (MI) or for patients with NIHA class IV symptoms who are
not candidates for advanced therapy.
Cardiac pacemaker resinchronization (CRT) therapy is recommended for
symptomatic HFrEF with EF <35% in sinus rhythm with left bundle
branch block (LBBB) for 150 ms despite GDMT. It is also recommended
for HFrEF with EF <35% regardless of the symptoms or duration of
heart failure if there is a high degree of atrioventricular (AV)
block with the need for a pacemaker. (FIGURE 3)
FIGURE 3. Strategic review of care for patients
with heart failure and reduced left ventricular ejection fraction (HFrEF)
LEGEND: b.p.m = beats per minute; BTC = bridge to
transplant candidate; BTT = bridge to heart transplant; CABG =
surgical coronary artery bypass grafting; CRT-D = defibrillator
pacemaker resynchronization; CRT-P = pacemaker for cardiac
resynchronization; DT = definitive therapy; ICD = implantable
cardioverter-defibrillator; ISDN = isosorbide dinitrate; LBBB =
block of the left branch of the His bundle; MCS = mechanical
circulation support; MV = mitral valve; PVI = radiofrequency
isolation of pulmonary veins; SAVR = surgical replacement of the
aortic valve; SR = sinus rhythm; TAVI = transcatheter replacement of
the aortic valve; TEE MV repair = transcatheter MV reconstruction
from edge to edge.
Color code for recommendation class: green for recommendation class
I; Yellow for recommendation class IIa. The figure shows the
management options with Class I and IIa recommendations. See special
tables for those with Class IIb recommendations.
Available at www.escardio.org/guidelines (doi: 10.1093/eurheartj/ehab368)
For HFmEF, diuretics are recommended to alleviate or eliminate
congestion. ACE inhibitors / angiotensin receptor blockers / ARNI /
beta-blockers / mineralocorticoid receptor antagonists may be
considered as adjunctive therapy to reduce mortality and
hospitalization (Class IIa recommendation).
Diagnosis and treatment of factors that contribute to heart failure
(hypertension, kidney disease, etc.) and the use of diuretics are
recommended for patients with heart failure with preserved left
ventricular ejection fraction (HFpEF). Specific therapies have not
been shown to reduce mortality in HFpEF. However, after the release
of the ESC guide (August 2021), a new registration study
Emperor-preserved (2) appeared, where empagliflozin showed
improvement in the clinical outcome of treatment in patients with
heart failure and preserved LVEF> 40%. A pooled analysis of the
effects of empagliflozin 10 mg daily with pre-existing drug therapy
for heart failure was performed on 9,718 Emperor-reduced and
Emperor-Preserved patients. These two studies were comparable so
that a wide range of left ventricular ejection fraction from 25% to
65% was obtained. Studies have shown that empagliflozin reduces the
risk of hospitalization due to heart failure in a wide range of
ejection fraction values by up to 65%, and its efficiency is reduced
in patients with LVEF> 65%. There is also a beneficial effect of
empagliflozin on symptoms and endurance effort consistently with an
ejection fraction of less than 65%. Further analysis found that the
size of the therapeutic response to empagliflozin did not depend on
the size of LVEF in the range of 25% to 65%, with a similar
reduction in HF hospitalization risk to LVEF size in subgroups <30%
and 40-50%, and in the subgroup with preserved left ventricular
ejection fraction> 50%. An important fact from these studies is that
empagliflozin reduces the risk of worsening glomerular filtration (GFR)
in HF along the entire spectrum of the ejection fraction of LVEF,
both with reduced, slightly reduced and preserved LVEF from 25% to
65% (2).
For all patients with HF, enrollment in a multidisciplinary HF
program, at home or at the clinic, is recommended. For the
prevention of HF, Class I recommendations include: appropriate
hypertension treatment, statin use, when indicated, SGLT2 inhibitors
in diabetics at high risk for or with cardiovascular disease, and
counseling to discontinue, consume alcohol and drugs, and treat
obesity.
For acute decompensated HF, routine use of inotropic drugs is not
recommended in the absence of cardiogenic shock, and routine use of
opioid-morphine is also not recommended for cardiogenic pulmonary
edema. Routine use of an intra-aortic balloon pump in cardiogenic
shock after myocardial infarction is not recommended.
Additional Class I recommendations for hospitalized patients with
acute HF include the introduction of targeted oral therapy and the
careful elimination of pre-discharge volume overload (congestion)
with early follow-up within 1-2 weeks of hospital discharge.
For patients with atrial fibrillation (AF), routine use of
anticoagulants for CHA2DS2-VASc ≥2 in men and ≥3 in women is
recommended, preferably with direct-acting oral anticoagulants (NOAC),
except in the presence of a prosthetic mechanical valve or moderate
or severe mitral stenosis. Recommended. Emergency cardioversion is
recommended for patients with HF AF who are hemodynamically
compromised. Rhythm control, including radiofrequency catheter
ablation, should be considered in AF patients who have symptoms.
For patients with HF and severe aortic stenosis, transcatheter /
surgical replacement of the aortic valve using the Heart Time
approach is recommended. For patients with HF with secondary mitral
regurgitation, percutaneous edge-to-edge mitral valve repair should
be considered if severe symptoms persist despite appropriate guided
therapy (GDMT). For patients with secondary mitral regurgitation and
coronary artery disease requiring revascularization, coronary
by-pass and mitral valve surgery should be considered.
Patients with cancer who are being considered for cardiotoxic
chemotherapeutic drugs and who are at risk of cardiotoxicity should
ideally be evaluated by a cardio-oncologist before starting therapy.
Tafamidis is a Class I recommendation in patients with TTR-type
amyloidosis with symptoms of NIHA class I-II.
All patients with HF should be periodically examined for iron
deficiency anemia. Administration of ferric carboxymaltose should be
considered in symptomatic, outpatient patients with HF and anemia
due to iron deficiency and EF ≤45% or hospitalized patients with HF
with EF ≤50%.
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