Author + information
- Received October 24, 2018
- Revision received February 6, 2019
- Accepted March 7, 2019
- Published online May 27, 2019.
- Peter van der Meer, MD, PhDa,∗,
- Hanna K. Gaggin, MD, MPHb,∗@HannaGaggin and
- G. William Dec, MDb,∗ (, )@MassGeneralNews
- aDepartment of Cardiology, University Medical Center Groningen, Groningen, the Netherlands
- bCardiology Division, Massachusetts General Hospital, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. G. William Dec, Cardiology Division, Massachusetts General Hospital, Yawkey 5B, Boston, Massachusetts 02114.
• HF is a highly prevalent, progressive condition associated with substantial morbidity and mortality.
• Practice HF guidelines provide a contemporary, evidence-based approach to its diagnosis and management.
• Guideline recommendations from the American College of Cardiology and European Society of Cardiology for differing HF phenotypes have similarities and discordances.
• Although effective treatment options exist for HF with reduced ejection fraction, new therapies for HF with preserved ejection fraction and AHF are urgently needed.
The 2013 (with updates in 2016 and 2017) American College of Cardiology/American Heart Association and 2016 European Society of Cardiology guidelines provide practical evidence-based clinical guidelines for the diagnosis and treatment of both acute and chronic heart failure (HF). Both guidelines address noninvasive and invasive testing to establish the diagnosis of HF with reduced ejection fraction and HF with preserved ejection fraction. Extensive trial evidence supports the use of guideline-directed medical therapy and device-based therapies for the optimal management of patients with HF with reduced ejection fraction. Specific recommendations are also provided for HF with preserved ejection fraction although the evidence is substantially weaker. Management of medical comorbidities is now addressed in both guidelines. Acute HF and end-stage disease requiring advanced therapies are also discussed. This review compares specific recommendations across the spectrum of HF phenotypes and disease severity, highlights areas where differences exist, and lists consequential studies published since the latest guidelines.
Practice guidelines from the American College of Cardiology/American Heart Association (ACC/AHA) and the European Society of Cardiology (ESC) provide clinicians with an evidence-based approach to the management of patients with acute or chronic heart failure (HF). The guidelines have been developed by content experts and are updated regularly to reflect new clinical data, particularly related to pivotal findings from randomized controlled trials. The ACC/AHA guidelines (ACCG) were extensively updated in 2013 and had focused updates in 2016 and 2017 (1–3). The ESC guidelines (ESCG) were most recently revised in 2016 (4). Consequently, recommendations vary based upon differences in the timing of available data and weighting of results among consensus panels. Both guidelines provide recommendations by class and level of evidence (Table 1). Although their scope is broad, many recommendations focus on the management of chronic HF with reduced ejection fraction (HFrEF). This reflects the many positive clinical trials showing efficacy of pharmacological and device-based therapies in this population. Specific recommendations are provided regarding the management of HF with preserved ejection fraction (HFpEF), but treatments have largely proven ineffective in this condition. The guidelines also focus on strategies aimed at prevention of HF and the early treatment of asymptomatic left ventricular (LV) dysfunction. Similarly, greater recognition of the importance of medical comorbidities has led to specific treatment recommendations. This review summarizes major recommendations regarding the diagnosis and treatment of cardiomyopathies and symptomatic HF. Although both guidelines have many similarities (Figure 1), differences are also highlighted (Central Illustration). Finally, important new studies that have been published after the guidelines are summarized within relevant sections because they may influence future guideline revisions (Table 2).
Classifications of Disease: Background
The clinical syndrome of HF may result from disorders of the pericardium, myocardium, endocardium, or heart valves. However, most patients have symptoms related to impaired LV myocardial function. Abnormalities of systolic and diastolic function coexist, irrespective of ejection fraction. LV ejection fraction (LVEF) remains crucial in classification because it was originally used to differentiate HFrEF and evaluate its pathophysiology and response to therapy. Clinical trials that have demonstrated a mortality benefit have been in this population. HFrEF is defined by clinical HF syndrome with LVEF ≤40%, whereas HFpEF encompasses HF patients with LVEF ≥50%. ESC criteria require additional supportive findings beyond signs or symptoms of HF and include elevated levels of natriuretic peptide, and objective evidence of structural or functional alterations. Key structural abnormalities include left atrial enlargement or increased LV mass; functional alterations consistent with diastolic dysfunction including E/e′ >13 and a mean e′ septal and lateral wall <9 cm/s (5). A third group has been recently characterized—HF with mid-range ejection fraction (HFmrEF) (LVEF = 40% to 49%).
Onset of HF may be delayed or prevented by interventions aimed at modifying risk factors (stage A) or treating asymptomatic LV dysfunction (stage B). Hypertension is a major risk factor for the development of both HFrEF and HFpEF, and treatment has been shown to reduce the risk of incident HF by approximately 50%. Diuretic agents, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or beta-blockers have all been shown effective and are recommended in both guidelines. ESCG also comments on the results of the SPRINT study (Systolic Blood Pressure Intervention Trial), which demonstrated that hypertension should be treated to a lower goal (systolic blood pressure <120 mm Hg) in older hypertensive patients or those at high risk (6). Both guidelines recommend aggressive treatment with statin therapy in patients with or at high risk of coronary artery disease, smoking cessation, and limitation in alcohol intake.
Obesity and insulin resistance, with or without overt diabetes mellitus, are important risk factors for HF development. ESCG cite recent data on the effectiveness of empagliflozin (a sodium-glucose transporter-2 inhibitor) in reducing mortality and HF hospitalizations (7); other classes of agents have not been shown to reduce the risk of cardiovascular events and may increase the risk of HF (e.g., pioglitiazone).
Biomarkers may also be of use in identifying patients at risk. The STOP-HF trial (St. Vincent's Screening To Prevent Heart Failure Study) evaluated patients >40 years of age with either cardiovascular risk factors or cardiac disease, and found that collaborative care for patients with minor elevation in B-type natriuretic peptide (BNP) reduced the combined rate of LV systolic dysfunction and overt HF (8). Similarly, serial use of biomarkers (BNP and/or troponin) in conjunction with serial echocardiography may help identify at-risk patients receiving cardiotoxic chemotherapeutic regimens (particularly, anthracyclines or trastuzumab). However, neither guideline yet recommends this approach.
Asymptomatic LV Dysfunction/Stage B Disease
All recommendations for stage A patients also apply to those with stage B disease. ACCG also provide for the use of ARBs to prevent HF in post-myocardial infarction (MI) LV dysfunction (Class of Recommendation [COR]: I) ESCG also recommend ACE inhibitor therapy for patient with stable coronary artery disease (CAD) even without LV systolic dysfunction (COR: IIa). ACE inhibitors have been shown to reduce the risk of HF in asymptomatic patients with chronically reduced LVEF, regardless of etiology. ACCG recommend beta-blockers for all patients with reduced ejection fraction (COR: I), whereas ESCG recommend their use for patients with prior MI (COR: I) and recognize that data are more limited for nonischemic LV dysfunction. Neither guideline yet suggests the use of a mineralocorticoid receptor antagonist (MRA) to prevent LV remodeling.
The diagnostic approach to the patient with suspected HF is relatively similar between guidelines (Table 3). Although both indicate that routine genetic testing in unexplained cardiomyopathies is not yet indicated (1,4), recent HF Society of America guidelines recommend genetic testing for patients with unexplained cardiomyopathy (9). The most severely affected family member should be tested, and cascade genetic screening of at-risk family members performed. In dilated cardiomyopathy, there is now evidence for prognostic and management implications.
Both guidelines clearly confirm the clinical utility of serum BNP or N-terminal pro–B-type natriuretic peptide (NT-proBNP) for establishing disease and prognosis in chronic HF, regardless of etiology. Measurement of baseline levels of natriuretic peptide and cardiac troponin on admission are useful to establish prognosis in acute HF (AHF) (3). Similarly, pre-discharge natriuretic peptide level can help establish post-discharge prognosis (3). The role of other biomarkers of myocardial fibrosis (e.g., ST2 and galectin-3) is less well established (COR: IIb). Although BNP and NT-proBNP levels decrease with treatment, and a decline in levels over time generally correlates with improved clinical outcomes, biomarker “guided” therapy has produced inconsistent results in randomized controlled trials (RCTs) (10). Consequently, data are insufficient to inform specific guideline recommendations related to natriuretic peptide-guided therapy or serial measurement of BMP or NT-proBNP for the purpose of reducing hospitalizations or mortality (2).
Transthoracic echocardiography plays a pivotal role in establishing HF phenotype (i.e., HFrEF vs. HFpEF or HFmrEF). Repeat measurement is useful in patients who have significant changes in clinical status or receive treatment that may promote cardiac remodeling. ESCG specify criteria for assessing diastolic function when symptoms due to HFpEF are suspected. They also recommend systolic tissue Doppler velocities and strain imaging in patients at risk of developing HF in order to identify myocardial dysfunction in the preclinical stage (COR: IIa). Transesophageal echocardiography should be considered when the severity of mitral or aortic valve disease does not match the patient's symptoms or transthoracic echocardiogram findings.
ACCG suggest noninvasive assessment to detect ischemia among patients with de novo HF and known coronary disease, but lack angina, unless the patient is not eligible for revascularization (COR: IIa). Viability assessment is also considered reasonable when planning revascularization among patients with HF and depressed ejection fraction (COR: IIa). ESCG are somewhat more conservative and indicate noninvasive stress imaging (cardiac magnetic resonance, stress echo, single-photon emission computed tomography, or positron emission tomography) may be considered for assessment of myocardial ischemia and viability (COR: IIb). Results from the randomized STICH (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease) trial have significantly tempered enthusiasm for viability testing in the United States (11). Cardiac computed tomography angiography may be considered for patients with a low-to-intermediate pre-test probability of coronary disease or those with equivocal noninvasive stress test (COR: IIb).
Cardiac magnetic resonance imaging indications are more detailed in ESCG. Cardiac magnetic resonance is recommended for myocardial tissue characterization in suspected inflammatory or infiltrative diseases (e.g., myocarditis, amyloidosis) and in patients with complex congenital heart disease (COR: I). Both recommend that cardiac magnetic resonance with late gadolinium enhancement be considered to distinguish between ischemic and nonischemic myocardial damage and to assess the amount of scarring (COR: IIa) (2,4,13).
Coronary angiography is recommended by ESCG in patients with HF and angina pectoris, and those with a history of ventricular arrhythmias or aborted cardiac death (COR: I). Both guidelines suggest that angiography be considered when ischemia is felt to be contributing to HF or in patients with intermediate-to-high pre-test probability of coronary disease in the presence of ischemia on noninvasive stress testing (COR: IIa). Hemodynamic assessment with right heart catheterization is recommended for patients with severe HF being considered for heart transplantation or mechanical circulatory support (COR: I). Both guidelines suggest that invasive hemodynamic monitoring is potentially useful in selected patients with persistent HF symptoms despite standard therapies, require vasopressor support, or have uncertain volume or perfusion status.
Endomyocardial biopsy is not recommended for routine assessment of unexplained cardiomyopathy (COR: III). Both guidelines suggest endomyocardial biopsy should be considered in patients with rapidly progressive HF despite treatment, worsening ventricular dysfunction, or for specific conditions where therapy is available and effective (e.g., sarcoidosis, giant cell myocarditis) (14).
Pharmacological Treatment HFrEF
Both guidelines are highly concordant for treating HFrEF (Table 4). This is not surprising, because treatment recommendations have been based on extensive RCT results. Guideline-directed medical therapy (GDMT) is the cornerstone of pharmacological therapy for HFrEF. Both guidelines recommend the use of loop diuretic agents in patients who have symptoms or signs for volume overload.
Neurohormonal antagonists (ACE inhibitors, MRAs, and beta-blockers) have all been shown to decrease HF hospitalizations and improve survival, and are recommended for the treatment of all patients with current or prior HF symptoms, unless contraindicated or not tolerated (COR: I). Both guidelines recommend the use of ACE inhibitor therapy for patients with current or prior HF symptoms. ARB treatment is considered acceptable as an alternative vasodilator for patients intolerant of ACE inhibitors (ESCG COR: I) or as a first-line alternative to ACE inhibitor treatment (ACCG COR: I). The role of angiotensin receptor-neprilysin inhibitors (ARNIs) is rapidly expanding. The use of an ARNI (specifically, sacubitril/valsartan) now receives a Level I recommendation by ACCG for New York Heart Association (NYHA) functional class II/III patients who have been stable on a prior regimen of ACE inhibitor or ARB; ESCG suggest it as a replacement for an ACE inhibitor in ambulatory patients who remain symptomatic despite optimal treatment with ACE inhibitors, beta-blockers, and MRAs.
Beta-blocker therapy is recommended for all patients with stable, symptomatic HF (NYHA functional class II to IV) to reduce the risk of HF hospitalization and death. Beta-blockers and ACE inhibitors are complementary and can be started together once the diagnosis of HFrEF has been made. ACCG recommend the use of a specific beta-blocker (e.g., bisoprolol, carvedilol, or sustained-release metoprolol succinate), whereas ESCG do not dictate specific drugs.
Adding MRAs (e.g., spironolactone or eplerenone) to ACE inhibitors (or ARB if intolerant of ACE inhibitors) and beta-blockers is recommended in patients with NYHA functional class II to IV HF who have LVEF ≤35% to reduce morbidity and mortality by both guidelines. These agents are also recommended in both guidelines following acute MI in patients with LVEF <40% who developed symptomatic HF or have a history of diabetes mellitus. However, recent studies suggest no benefit among acute MI patients with depressed LV function in the absence of a history of HF signs or symptoms (15). Both guidelines caution against the use of aldosterone receptor antagonist in the presence of renal insufficiency (estimated glomerular ejection fraction <30 ml/min/1.73 m2 or serum potassium >5.0 mEq/l) (1,4).
Ivabradine is a new therapeutic agent that selectively inhibits the If current in the sinoatrial node, providing heart rate reduction. Both guidelines suggest that ivabradine should be considered for persistently symptomatic patients with LVEF ≤35%, in sinus rhythm and with a resting heart rate ≥70 beats/min despite evidence-based dosing of beta-blocker (or maximally tolerated dose) (COR: IIa). ESCG also suggest its use for symptomatic patients who are unable to tolerate or have contraindications to beta-blocker therapy (COR: IIa), but data are limited on its efficacy in this population (16).
Digoxin has a very limited role and may be considered in symptomatic patients in sinus rhythm despite GDMT to reduce all-cause and HF hospitalizations (ESCG COR: IIb) (1,4). It is often still used for rate control in rapid atrial fibrillation (AF) but should be considered when other therapeutic options prove ineffective.
Despite the substantial proven benefits of GDMT, significant gaps in the use and dosing remain in contemporary practice. The CHAMP-HF (Change the Management of Patients With Heart Failure) registry recently demonstrated that among eligible patients, 27%, 33%, and 67% were not prescribed ACE inhibitor/ARB/ARNI, beta-blocker, and MRA therapy, respectively (16). Further, when prescribed, <30% of patients were receiving the recommended doses of ACE inhibitor/ARB/ARNI or beta-blocker.
Both guidelines are largely concordant regarding the use of nonsurgical devices in HFrEF patients (Table 5). Irrespective of LV function, an implantable cardioverter-defibrillator (ICD) reduces mortality in sudden cardiac death survivors and patients with sustained ventricular tachycardia (COR: IA). In primary prevention, most evidence comes from patients with an ischemic etiology, and in both guidelines, an ICD is recommended in patients with LVEF ≤35% despite >3 months of treatment with optimal pharmacological therapy to reduce the risk of sudden death. Patient with NYHA functional class I are not explicitly discussed in the ESCG, whereas the ACCG give a Class IB recommendation for these patients if LVEF ≤30%.
Both guidelines recommend against an ICD in patients within 40 days after MI, on the basis of negative RCTs that showed no early benefit (17). Given these results, the VEST (Vest Prevention of Early Sudden Death Trial and VEST Registry) was designed to study the effect of a wearable cardioverter-defibrillator during this high-risk period after MI (18). Interestingly, the use of a wearable cardioverter-defibrillator did not result in a significantly lower rate of sudden cardiac death in patients with a recent MI and LVEF ≤35%. In the ESCG, a wearable cardioverter-defibrillator received a COR: IIb, Level of Evidence (LOE): C recommendation, but these results will most likely downgrade this recommendation in the future.
In patients with HFrEF with a nonischemic etiology, the strength of evidence had become weaker at the time of writing the guidelines. The DEFINITE (Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation) trial, which included only patients with a nonischemic etiology, showed merely a trend toward lower mortality (19). Therefore, in both guidelines, the LOE is lower than for patients with an ischemic etiology (i.e., COR: I, but LOE: B). However, this may require reconsideration, given the publication of the DANISH trial (20). The DANISH trial (Danish ICD Study in Patients With Dilated Cardiomyopathy) failed to show a mortality benefit of ICD in patients with nonischemic HF. Only in a subgroup of patients <68 years of age was a beneficial effect on mortality observed.
Cardiac resynchronization therapy
Both guidelines are largely concordant regarding the role of cardiac resynchronization therapy (CRT). Clinical and echocardiographic benefit is the most clear cut among patients with LVEF <35%, markedly prolonged QRS duration (>150 ms), left bundle branch block (LBBB) morphology, and in sinus rhythm. The EchoCRT (Echocardiography Guided Cardiac Resynchronization Therapy) trial showed potential harm of CRT in patients with QRS duration <130 ms (21), which was also observed in an individual patient data meta-analysis. The ESCG clearly state that CRT implantation is not recommended in patients with a QRS duration <130 ms. ACCG guidelines use a cutoff value of >120 ms to define potential benefit; however, this will likely change. Furthermore, both guidelines underline that evidence has become less clear when the QRS morphology is non-LBBB, QRS duration is between 130 and 150 ms, and in patients with AF. In these situations, differences exist between guidelines, where the ESCG give a IIb recommendation for patients with non-LBBB and QRS duration of 130 to 149 ms, the ACCG give a COR: III (no benefit) recommendation. There is a current debate whether duration or morphology of the QRS complex is the main driver of response to CRT (22). None of the landmark CRT trials selected patients based on QRS morphology, and meta-analysis of the large CRT trials suggested that QRS duration was the main determinant of CRT response. However, the vast majority of patients (78%) in CRT trials had LBBB morphology.
The evidence for CRT in patients with AF is also less certain. Most large trials excluded patients with AF. A subgroup analysis of the RAFT (Resynchronization for Ambulatory Heart Failure Therapy) trial showed that patients with AF had no benefit from CRT compared with ICD alone; however, less than one-half of the patients had >90% biventricular capture (23). Both guidelines, therefore, give a lower recommendation to patients with AF (COR: IIa, LOE: B), and both state that a strategy to ensure near 100% biventricular capture should be in place (atrioventricular nodal ablation or rate control).
Pharmacological Treatment of HFpEF
In contrast to HFrEF, no therapies have been shown to definitively improve mortality or hospitalization in HFpEF (Table 6). Therefore, emphasis from both guidelines (1,2,4) has been on symptom management with diuretic agents in patients with excess volume, as well as aggressive risk factor management for comorbidities. ESCG mention the use of candesartan for improvement in NYHA functional class, but does not fully endorse its use on the basis of inconsistent evidence for improvement in symptoms in HFpEF patients treated with concomitant ARBs and ACE inhibitors.
ESCG recommend aggressively screening and managing both cardiovascular as well as noncardiovascular comorbidities according to standard GDMT (COR: I). ESCG specifically address AF and the need for anticoagulation and the use of GDMT to control hypertension, CAD, and myocardial ischemia. Diabetes mellitus is associated with a specific recommendation of metformin as a first-line oral hypoglycemic drug; empagliflozin, an SGLT2 inhibitor, has recently been associated with a reduction in HF hospitalization and cardiovascular mortality (COR: IIb). ESCG also mention the benefit of exercise training for improving exercise capacity and diastolic function. ACCG also focus on recommendations for specific cardiovascular comorbidities: treatment of hypertension (COR: I), CAD (COR: IIa), and AF (COR: IIa) using GDMT.
Although the data are quite limited, both guidelines discuss medications that may reduce HF hospitalizations. ESCG mention studies potentially supporting the use of nebivolol, digoxin, spironolactone, or candesartan for patients in sinus rhythm (4). ACCG provide a Class IIb recommendation for ARB and MRA for reducing HF hospitalizations (1). Recommendations for MRA use is limited to selected HFpEF patients (LVEF ≥45%, elevated natriuretic peptide levels or HF hospitalization within the past year, and absence of contraindications) on the basis of a subgroup analysis of the TOPCAT (Treatment of Preserved Cardiac Function HF with an Aldosterone Antagonist) trial (24). However, it must be recognized that hospitalizations and deaths are more likely to be due to noncardiovascular causes in HFpEF patients. A variety of phase 2 and 3 trials of novel therapies for HFpEF, including sacubitril/valsartan (e.g., the PARAGON-HF [Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction], PARALLAX [A Randomized, Double-blind Controlled Study Comparing LCZ696 to Medical Therapy for Comorbidities in HFpEF Patients], and PERSPECTIVE [Efficacy and Safety of LCZ696 Compared to Valsartan on Cognitive Function in Patients With Chronic Heart Failure and Preserved Ejection Fraction] trials) and SGLT2 inhibitors (e.g., EMPEROR-PRESERVED [EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction], PRESERVED-HF [Dapagliflozin in PRESERVED Ejection Fraction Heart Failure], DELIVER [Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure], and ERADICATE-HF [ERtugliflozin triAl in DIabetes With Preserved or Reduced ejeCtion FrAcTion mEchanistic Evaluation in Heart Failure] trials) are underway.
Selected Comorbidities and HF
AF is more common among HF patients and correlates closely with HF severity. The relationship between HF and AF is complex; AF is a risk factor for developing HF (e.g., AF with rapid ventricular rate may result in a tachycardia-mediated dilated cardiomyopathy), and patients with HF are more likely to develop AF over time. In addition, symptoms of HF often coexist with AF and can complicate symptom management.
ACCG and ESCG are generally in agreement; this includes identification and correction of reversible causes of AF (evaluation recommendations are detailed in ACCG), assessment of thromboembolic risk and anticoagulation need, rate control, and symptom management.
For patients who develop HF as a result of AF and rapid ventricular rate, either rhythm control (initiate amiodarone 1 month before cardioversion and continue <6 months) or rate control is recommended by ACCG, whereas ESCG allude to the fact that either method works to resolve HF.
In HF patients who develop AF subsequently, rhythm control has not been shown to be superior to a rate-control strategy (25). ESCG support rhythm control over rate control in the setting of reversible secondary cause of AF or refractory symptoms of AF despite adequate rate control and HF management. Although no definitive evidence exists on the optimal ventricular rate in patients with AF and HF, ESCG describe optimal heart rates between 60 and 100 beats/min, with 1 study suggesting that up to 110 beats/min may be acceptable (26), and lower ventricular rate <70 beats/min may be associated with a worse outcome.
ACCG recommend beta-blockade as the first-line rate-control medication with digoxin as an adjunctive medication, whereas ESCG discuss the preferential use of oral or intravenous digoxin in patients with volume overload, and intravenous amiodarone and digoxin in patients with hemodynamic instability. In patients with hemodynamic collapse, emergent cardioversion is recommended. ACCG take a more lenient position regarding the use of non-dihydropyridine calcium antagonists such as diltiazem (should be used with caution in patients with HFrEF, whereas it can be used in those with HFpEF, often with digoxin), whereas ESCG generally recommend avoiding their use if possible in HFrEF and with less certainty in HFpEF and HFmrEF. For AF and rapid ventricular response that is refractory despite maximal pharmacological therapy, atrioventricular node ablation and CRT may be useful. Results of trials of catheter ablation as a part of rhythm control strategy have not been definitive, but a small trial suggests that this approach may be useful in carefully selected HF patients (27).
Both guidelines agree that most HF patients would benefit from systemic anticoagulation unless contraindicated. ESCG prefer novel oral anticoagulant agents compared with vitamin K antagonists in HF patients with nonvalvular AF, but in patients with mechanical heart valves or at least moderate mitral stenosis, only vitamin K antagonists are recommended. In those at high risk for both thromboembolism and of bleeding, a left atrial occlusion device may be considered.
Both guidelines emphasize the importance of controlling hypertension in stage A to D HF. Although there is concordance that controlling blood pressure with antihypertensive medications is recommended to help prevent onset of HF, ACCG have extrapolated the findings of the SPRINT trial (6) to the HFrEF population with the caveat that antihypertensive medications should include GDMT such as ACE inhibitors, ARB, beta-blockers, ARNI, and MRAs with a systolic blood pressure goal <130 mm Hg. ESCG recommend a similar set of medications, but do not mention ARNI or a specific blood pressure.
ESCG delineate which medications should be prioritized in HFrEF patients with hypertension: ACE inhibitors or ARB, beta-blockers, then MRA in the order of preference, then a diuretic agent, then amlodipine or hydralazine. Felodipine now receives a Class IIa recommendation for treatment failures.
Overall, ESCG discussion of treatment of medical comorbidities is more extensive and touches on specific disorders not mentioned in the ACCG including ischemic heart disease, cancer, diabetes mellitus, renal dysfunction, obesity, pulmonary disease, and valvular heart disease. For details, we would recommend referring to ESCG because such a discussion is outside the scope of this document.
AHF refers to a rapid onset or deterioration of signs and symptoms of HF. Initial management of AHF should focus on early identification of precipitants/causes leading to decompensation. Both guidelines explicitly mention these factors, including nonadherence to medication, acute myocardial ischemia, arrhythmias, and recent addition of medication including nonsteroidal anti-inflammatory drugs and negative inotropic drugs. The ESCG coined the acronym CHAMP (acute Coronary syndrome, Hypertensive emergency, Arrhythmias, Mechanical causes, acute Pulmonary embolism) to ensure rapid identification of causes leading to AHF. Furthermore, both guidelines recommend a classification based upon “congestive” signs and symptoms (wet or dry), and peripheral perfusion (warm or cold). ESCG also provide a management algorithm based upon these clinical profiles (4).
Unfortunately, little progress has been made in the treatment of AHF. The cornerstones of treatment still remain diuretic agents and vasodilators. Diuretic agents improve dyspnea in the short term and receive a Class I recommendation in both guidelines. For patients with insufficient response, a combination of a loop diuretic agent with a second diuretic agent (i.e., thiazide) should be considered (ESCG COR: IIb, ACCG COR: IIa). The recent ATHENA-HF (Study of High-dose Spironolactone vs. Placebo Therapy in Acute Heart Failure) did not find a beneficial role for high-dose (100 mg daily) spironolactone in the treatment of AHF (28).
Furthermore, the ACCG provide a Class IIb recommendation for the use of low-dose dopamine to improve diuresis and preserve renal function, whereas the ESCG do not comment on renal dopamine and restrict the use of inotropic agents to patients with hypotension and/or symptoms of hypoperfusion. Given the results of the ROSE trial (Renal Optimization Strategies Evaluation in Acute Heart Failure and Reliable Evaluation of Dyspnea in the Heart Failure Network Study) (29), which showed no effect of low-dose dopamine (or nesiritide) on decongestion or renal function, the ACCG Class IIb recommendation may be revised.
Ultrafiltration is occasionally considered for patients who are diuretic agent resistant. However, the CARRESS (Effectiveness of Ultrafiltration in Treating People With Acute Decompensated Heart Failure and Cardiorenal Syndrome) trial did not demonstrate a benefit of ultrafiltration compared with intravenous loop diuretic agents (30). At present, both guidelines provide ultrafiltration a Class IIb recommendation for patients with refractory congestion not responding to diuretic agents, and clearly mention that it is not recommended as a routine strategy in AHF.
Vasodilators can be used in most patients with AHF, but these drugs should be avoided in those with systolic blood pressure <90 mm Hg and used with caution in patients with severe mitral or aortic stenosis. The ESCG give a Class IIa recommendation for vasodilators, whereas the ACCG give a Class IIb recommendation. Vasopressors should be reserved for patients with severe hypotension to increase blood pressure and ensure blood supply to vital organs. A subgroup analysis of the SOAP II (Sepsis Occurrence in Acutely Ill Patients II) trial showed that in patients with cardiogenic shock, the use of noradrenaline resulted in a lower mortality compared with using dopamine.
Advanced HF, Mechanical Circulatory Support, and Heart Transplantation
The ACCG classify patients with advanced/end-stage HF as stage D. The ACCG clearly emphasize the importance of identifying patients with advanced HF. This has recently been further specified with an acronym “I-NEED-HELP” to identify patients that may benefit from a referral to a HF specialist (2,4). Both guidelines describe the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) as a useful to tool to stratify patients with advanced HF.
Mechanical circulatory support for temporary or long-term support is increasingly used in the treatment of patients with severe HFrEF who have failed GDMT. Both guidelines also recommend that short-term mechanical support (nondurable systems) including extracorporeal life support and extracorporeal membrane oxygenation should be used in patients with acute profound HF as “bridge to decision” to gain time for heart transplantation or a permanent assist device evaluation. Both guidelines recommend that the implantation of a permanent LV assist device should be considered in carefully selected patients with advanced HF (COR: IIa). The ESCG makes a distinction between LV assist device for bridge to transplant (COR: IIa LOE: C) and for patients who are not eligible for heart transplantation (COR: IIa, LOE: B) (4). Heart transplantation is still the best long-term treatment option for patients with advanced HF. The ACCG give evaluation for cardiac transplantation a COR: Ic, whereas the ESCG define heart transplantation as an accepted treatment of end-stage HF in carefully selected patients.
↵∗ Drs. van der Meer and Gaggin contributed equally to this work.
Dr. Gaggin is supported in part by the Clark Fund for Cardiac Research Innovation. Dr. van der Meer has served on the Speakers Bureau for Novartis, Vifor Pharma, Boston Scientific, and AstraZeneca; and has received research grant support from AstraZeneca, Corvidia, Ionis, and Vifor Pharma. Dr. Gaggin has received research grant support from Roche Diagnostics, Jana Care, Novartis, and Ortho Clinical; has received consulting income from Roche Diagnostics and Merck; and has received research payments for clinical endpoint committees from Radiometer. Dr. Dec has reported that he has no relationships relevant to the contents of this paper to disclose. Michele Hamilton, MD, served as Guest Associate Editor and P.K. Shah, MD, served as Guest Editor-in-Chief for this paper.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
- Abbreviations and Acronyms
- American College of Cardiology/American Heart Association
- American College of Cardiology/American Heart Association practice guidelines
- angiotensin-converting enzyme
- atrial fibrillation
- angiotensin receptor blocker
- angiotensin receptor-neprilysin inhibitor
- B-type natriuretic peptide
- coronary artery disease
- Class of Recommendation
- cardiac resynchronization therapy
- European Society of Cardiology
- European Society of Cardiology guidelines
- guidelines-directed medical therapy
- heart failure
- heart failure with mid-range ejection fraction
- heart failure with preserved ejection fraction
- heart failure with reduced ejection fraction
- implantable cardioverter-defibrillator
- left bundle branch block
- Level of Evidence
- left ventricular
- left ventricular ejection fraction
- myocardial infarction
- mineralocorticoid receptor antagonist
- N-terminal pro–B-type natriuretic peptide
- New York Heart Association
- randomized controlled trial
- Received October 24, 2018.
- Revision received February 6, 2019.
- Accepted March 7, 2019.
- 2019 American College of Cardiology Foundation
- Yancy C.W.,
- Jessup M.,
- Bozkurt B.,
- et al.
- Yancy C.W.,
- Jessup M.,
- Bozkurt B.,
- et al.
- Yancy C.W.,
- Jessup M.,
- Bozkurt B.,
- et al.
- Ponikowski P.,
- Voors A.A.,
- Anker S.D.,
- et al.
- Hsu J.J.,
- Ziaeian B.,
- Fonarow G.C.
- Hershberger R.E.,
- Givertz M.M.,
- Ho C.Y.,
- et al.
- Felker G.M.,
- Anstrom K.J.,
- Adams K.F.,
- et al.
- Ferreria V.M.,
- Schulz-Menger J.,
- Holmvang G.,
- et al.
- Cooper L.T.,
- Baughman K.L.,
- Feldman A.M.,
- et al.
- Beygui F.,
- Cayla G.,
- Roule V.,
- et al.
- Greene S.J.,
- Butler J.,
- Albert N.M.,
- et al.
- Olgin J.E.,
- Pletcher M.J.,
- Vittinghoff E.,
- et al.,
- VEST Investigators
- Poole J.E.,
- Singh J.P.,
- Birgersdotter-Green U.
- Healey J.S.,
- Hohnloser S.H.,
- Exner D.V.,
- et al.,
- RAFT Investigators
- Marrouche N.F.,
- Brachmann J.,
- Andresen D.,
- et al.,
- CASTLE-HF Investigators
- Arnold A.D.,
- Shun-Shin M.J.,
- Keene D.,
- et al.
- Velazquez E.J.,
- Morrow D.A.,
- DeVore A.D.,
- et al.
- Stone G.W.,
- Lindenfeld A.J.,
- Abraham W.T.,
- et al.,
- COAPT Investigators
- Obadia J.F.,
- Messika-Zeitoun D.,
- Leurent G.,
- et al.,
- MITRA-FR Investigators
- Central Illustration
- Classifications of Disease: Background
- Preventive Strategies
- Asymptomatic LV Dysfunction/Stage B Disease
- Diagnostic Evaluation
- Pharmacological Treatment HFrEF
- Device-Based Therapies
- Pharmacological Treatment of HFpEF
- Selected Comorbidities and HF
- Advanced HF, Mechanical Circulatory Support, and Heart Transplantation