Reproduced from: Bauersachs J, de Boer RA, Lindenfeld J, Bozkurt B. The year in cardiovascular medicine 2021: heart failure and cardiomyopathies. Eur Heart J. 2022 Feb 3;43(5):367-376. doi: 10.1093/eurheartj/ehab887, by permission of Oxford University Press on behalf of the European Society of Cardiology.
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In the year 2021, the universal definition and classification of heart failure (HF) was published that defines HF as a clinical syndrome with symptoms and/or signs caused by a cardiac abnormality and corroborated by elevated natriuretic peptide levels or objective evidence of cardiogenic congestion. This definition and the classification of HF with reduced ejection fraction (HFrEF), mildly reduced, and HF with preserved ejection fraction (HFpEF) is consistent with the 2021 ESC Guidelines on HF. Among several other new recommendations, these guidelines give a Class I indication for the use of the sodium–glucose co-transporter 2 (SGLT2) inhibitors dapagliflozin and empagliflozin in HFrEF patients. As the first evidence-based treatment for HFpEF, in the EMPEROR-Preserved trial, empagliflozin reduced the composite endpoint of cardiovascular death and HF hospitalizations. Several reports in 2021 have provided novel and detailed analyses of device and medical therapy in HF, especially regarding sacubitril/valsartan, SGLT2 inhibitors, mineralocorticoid receptor antagonists, ferric carboxymaltose, soluble guanylate cyclase activators, and cardiac myosin activators. In patients hospitalized with COVID-19, acute HF and myocardial injury is quite frequent, whereas myocarditis and long-term damage to the heart are rather uncommon.
U 2021.godini objavljena je Univerzalna definicija i klasifikacija zatajivanja srca (HF) koja HF definira kao klinički sindrom sa simptomima i/ili znakovima koje uzrokuje poremećaj srca i potvrđen povišenim vrijednostima natrijuretskog peptida ili objektivnim pokazateljima kongestije. Ova definicija i klasifikacija HF-a sa sniženom ejekcijskom frakcijom (HFrEF), blago sniženom, i HF-a s očuvanom ejekcijskom frakcijom (HFpEF) u skladu je sa Smjernicama Europskog kardiološkog društva (ESC) za HF. Među ostalim novim preporukama, te su smjernice dale klasu I. preporuke za uporabu inhibitora natrij-glukoza kotransportera 2 (SGLT2) dafagliglozina i emfagliflozina u bolesnika s HFrEF-om. Kao prva terapija utemeljena na dokazima za HFpEF, u istraživanju EMPORER-Preserved, empagliflozin je smanjio zajednički ishod kardiovaskularne smrti i hospitalizacija zbog HF-a. Više radova u 2021. godini pridonijelo je novom i cjelovitom pristupu liječenju HF-a, posebice sakubitril/valsartan, SGLT2 inhibitori, antagonisti mineralokortikosteroidnih receptora, željezove karboksimaltoze, aktivatori solubilne gvanilat ciklaze i aktivatora srčanog miozina. U bolesnika hospitaliziranih zbog bolesti COVID-19, akutni HF i oštećenje miokarda vrlo su česti, dok su miokarditis i dugotrajna oštećenja srca prilično rijetka pojava.
Heart failure (HF) remains a major challenge for patients and healthcare systems worldwide. For patients suffering from HF with reduced ejection fraction (HFrEF), several evidence-based treatments are available and have markedly improved prognosis and quality of life; however, a subset of these patients displays a rapid progression of HF despite best care. A recent special article called to action for global approaches to novel drug solutions for these patients, (
In this article, we summarize important progress that has been made in 2021 regarding the diagnosis and treatment of HF with a special focus on articles published in 2021 in the European Heart Journal and the European Journal of Heart Failure.
With the recognition of the need for standardization of an HF definition, the Universal Definition and Classification of Heart Failure was developed, which defined HF as a clinical syndrome with current or prior symptoms and or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide (NP) levels or objective evidence of cardiogenic pulmonary or systemic congestion by diagnostic modalities (
GRAPHICAL ABSTRACT. Summary of the universal definition and EF classification of heart failure; management of HFrEF according to 2021 ESC guidelines for heart failure and results of the EMPEROR-preserved trial. (from Bauersachs J, de Boer RA, Lindenfeld J, Bozkurt B. The year in cardiovascular medicine 2021: heart failure and cardiomyopathies. Eur Heart J. 2022 Feb 3;43(5):367-376. doi: 10.1093/eurheartj/ehab887, by permission of OUP on behalf of the ESC).
Please see Figure 1 in the original article.
The HF Atlas survey reports a wide-ranging incidence of HF and HF hospitalizations across Europe with considerable heterogeneity in the resources for management and the data quality providing data to allow the development of strategies to improve inequalities. (
Long-term joint exposure to various air pollutants, including PM2.5, PM10, PM2.5–10, NO2, and NOx is associated with an elevated risk of incident heart failure in an additive manner. Persons with genetic higher susceptibility to heart failure displayed a particularly high risk of heart failure. Reprinted with permission from Wang
A recent European registry report demonstrated that dilated cardiomyopathy (DCM), not skeletal myopathy, is the major determinant of prognosis in patients with dystrophin gene mutations. (
For HFrEF, the main diagnostic criterion remains LVEF ≤40%. (
There is increasing appreciation that classical diagnostics fall short in complex multifactorial diseases with various aetiologies and precipitants, and several studies have addressed whether an agnostic approach, where large data sets are queried by computer algorithms, may be superior in making a specific diagnosis. Such techniques are referred to as machine learning (ML) and artificial intelligence (AI). Peyster et al. (
Artificial intelligence/machine learning might be particularly useful for a diagnosis of HF. Kwon et al. (
In the near future, we will be faced with many more potential utility of AI/ML models, as there is a clear need for individualized approaches and decision-making. (
A state-of-the-art diagnosis of HF remains challenging. The ESC guidelines3 recommend using an array of signs and symptoms, supplemented with imaging and biomarkers studies. The imaging primarily relies on echocardiography and CMR, and NPs and high sensitivity troponins are the preferred biomarkers. However, sophisticated classification of patients in various categories using imaging and biomarkers may enhance adequate phenotyping, (
The 2021 ESC guidelines did not significantly change recommendations for acute HF, although the use of opioids was downgraded to a Class III recommendation. (
Mortality remains high in cardiogenic shock, and randomized trials assessing therapies remain rare but a single-centre trial randomized patients with cardiogenic shock to either milrinone or dobutamine and showed no differences in any of the primary or secondary outcomes. (
A single entry registry confirms that HeartMate III (HMIII) outcomes are better than historical controls confirming randomized trials. (
Women with a known cardiomyopathy or at risk for HF planning pregnancy, or presenting with HF during or after pregnancy are in need of individualized pre-, during, and post-pregnancy assessment and counselling. (
Patients with peripartum cardiomyopathy are at risk for detrimental outcomes (
In the health status analysis of EXPLORER-HCM, mavacamten markedly improved the health status of patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) compared with placebo. (
Heart failure often complicates the treatment of cancer, and a recent paper proposes definitions of cardiovascular (CV) toxicities. (
This field extends the increasing awareness that incident cancer is more common in patients with prevalent HF, (
NEW ALGORITHM OF THE 2021 ESC GUIDELINES ON HEART FAILURE FOR THE PHARMACOLOGICAL TREATMENT OF HEART FAILURE WITH REDUCED EJECTION FRACTION
The 2021 ESC Guidelines on HF provide a Class I recommendation for pharmacological treatment of all HFrEF patients with a combination of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor–neprilysin inhibitor (ARNI), a betablocker, a mineralocorticoid receptor antagonist (MRA), and a sodium–glucose co-transporter 2 (SGLT2) inhibitor (dapagliflozin or \and empagliflozin) (
A recent consensus document of the HFA of the ESC identified nine patient profiles that may be relevant for treatment implementation in patients with HFrEF taking into account heart rate, atrial fibrillation, symptomatic low blood pressure, estimated glomerular filtration rate, or hyperkalaemia. Using such a personalized approach may lead to a better and more comprehensive therapy for each individual patient. (
While ACE inhibitors are a standard for the prevention and treatment of HF for many years, the impact of these drugs as preventive therapy for HF in patients with Duchenne muscular dystrophy was unclear. A large French registry showed that prophylactic treatment of patients without LV dysfunction with an ACE inhibitor was able to prevent the transition to HF and improve survival in Duchenne muscular dystrophy. (
ANGIOTENSIN RECEPTOR–NEPRILYSIN INHIBITORS (PARAGON, PARADIGM, PARALLAX, PARADISE-MI, LIFE)
In an analysis of the PARADIGM-HF trial, initiation of sacubitril/valsartan, even when titrated to target dose, did not lead to greater discontinuation or down-titration of other guideline-directed medical therapies and was associated with fewer discontinuations of MRA. (
In the new 2021 ESC Guidelines on HF, (
SODIUM–GLUCOSE CO-TRANSPORTER 2 INHIBITORS (EMPEROR-REDUCED, EMPEROR-PRESERVED, DAPA-HF, SOLOIST)
Sodium–glucose co-transporter 2 inhibitors are rapidly becoming the panacea for the entire spectrum of cardiometabolic and renal disease. In trials in type 2 diabetes mellitus (T2DM), a beneficial effect was observed for CV endpoints in general, while the effects on incident HF were overwhelmingly positive. These effects were validated in patients with prevalent HFrEF, first in DAPA-HF and a year later in the EMPEROR-Reduced trial. Numerous subanalyses from these trials were published in 2021.
First, besides the striking effects on hard endpoints, it is more and more recognized that functional status and symptoms are important to patients with HFrEF. (
Different from HFrEF, the efficacy of SGLT2 inhibitors in HFpEF remained to be proven. However, the EMPEROR-Preserved study presented during ESC 2021 demonstrated that empagliflozin reduced the primary combined endpoint of CV death and HF hospitalization in almost 6000 patients with HFpEF (
Please see
Sodium–glucose co-transporter 2 inhibitors were also evaluated in patients with acute HF or immediately after acutely decompensated HF. The SOLOIST trial, (
Sodium–glucose co-transporter 2 inhibitors do not stop to amaze us in renal disease. After the publication of the hallmark trials CREDENCE and DAPA-CKD, (
MINERALOCORTICOID RECEPTOR ANTAGONISTS (FIDELIO, FIGARO, HOMAGE)
Mineralocorticoid receptor antagonists are first-line therapies for HFrEF and may also be considered in HFmrEF. (
The novel activator of soluble guanylate cyclase, vericiguat, in a subanalysis of the VICTORIA trial, did not reduce new-onset atrial fibrillation. However, pre-existing atrial fibrillation did not affect the beneficial effect of vericiguat on the primary composite outcome (time to CV death or first HF hospitalization) or its components. (
A substudy of the pivotal trial of the myosin activator omecamtiv mecarbil (GALACTIC-HF) in patients with HFrEF found that the drug reduced the primary endpoint of HF hospitalization and CV death more as EF declined with a 17% decrease in the lowest quartile (EF≤22%) and no benefit in the highest quartile (EF≥33%). (
Iron deficiency is related to worse outcomes in HF. The AFFIRM-AHF study demonstrated that in patients with LVEF, 50% and iron deficiency after a hospitalization for acute HF, i.v. treatment with ferric carboxymaltose did not only reduce HF hospitalizations but also results in clinically meaningful beneficial effects on quality of life. (
Iron deficiency also contributes to resistance to endogenous erythropoietin, an important cause of anaemia in HF. (
In a small clinical trial, CDR132L, an antisense oligonucleotide drug directed against miR-132 was well tolerated and seemed to be associated with cardiac functional improvement in HF patients. (
In 50 patients with idiopathic chronic DCM and parvovirus B19 persistence, i.v. immunoglobulin therapy did not significantly improve LV systolic function or functional capacity beyond standard medical therapy. (
In patients with HF, atrial fibrillation and a narrow QRS mortality and HF hospitalizations were reduced by atrioventricular junctional ablation and cardiac resynchronization therapy (CRT) compared with pharmacological treatment alone; this beneficial effect was similar in patients with LVEF≤35% and .35%. (
The US Valvular Disease Guidelines as well as the 2021 ESC Guidelines on valvular heart disease recently upgraded the recommendation for transcatheter mitral valve repair (TEER) for secondary (functional) mitral regurgitation (SMR) to a IIA recommendation for patients who meet COAPTcriteria. (
The GUIDE-HF trial evaluated haemodynamic guided management to reduce HF hospitalizations and mortality in patients with NYHA II-IV and all ejection fractions. The overall analysis was negative but when COVID-19 was accounted for there was a significant reduction in HF hospitalization in NYHA II-III patients with either a previous HF hospitalization or elevated NPs. (
In a comprehensive review, Bekfani and colleagues discuss unmet needs in the management of patients with HF, how remote monitoring might contribute to future solutions and provide an overview of current and novel remote monitoring technologies. (
In an Expert Panel consensus document on Cardiac Rehabilitation for Patients with Heart Failure, Bozkurt et al. (
Incident acute HF was recognized as a complication in 2%, and myocardial injury in 10% of all patients hospitalized with COVID-19. (
Myocardial injury in recovered COVID-19 patients assessed by cardiovascular magnetic resonance. Myocarditis-like injury can be encountered, with limited extent and minimal functional consequence. Reprinted with permission from Kotecha