Practical recommendations for the use of ACE inhibitors, beta-blockers, aldosterone antagonists and angiotensin receptor blockers in heart failure: putting guidelines into practice

Surveys of prescribing patterns in both hospitals and primary care have usually shown delays in translating the evidence from clinical trials of pharmacological agents into clinical practice, thereby denying patients with heart failure (HF) the benefits of drug treatments proven to improve well-being and prolong life. This may be due to unfamiliarity with the evidence-base for these therapies, the clinical guidelines recommending the use of these treatments or both, as well as concerns regarding adverse events. ACE inhibitors have long been the cornerstone of therapy for systolic HF irrespective of aetiology. Recent trials have now shown that treatment with beta-blockers, aldosterone antagonists and angiotensin receptor blockers also leads to substantial improvements in outcome. In order to accelerate the safe uptake of these treatments and to ensure that all eligible patients receive the most appropriate medications, a clear and concise set of clinical recommendations has been prepared by a group of clinicians with practical expertise in the management of HF. The objective of these recommendations is to provide practical guidance for non-specialists, in order to increase the use of evidenced based therapy for HF. These practical recommendations are meant to serve as a supplement to, rather than replacement of, existing HF guidelines.     

A Rationale for the Use of Anticoagulation in Heart Failure Management

Heart failure is a major public health concern for which treatment options have continued to evolve. While specific therapies such as beta blockers and angiotensin converting enzyme inhibitors have been shown to decrease hospitalizations and improve survival, the benefits of anticoagulation are less clear. Clinical guidelines detailing the appropriate use of anticoagulation for the management of atrial fibrillation and embolic stroke exist, but similar recommendations for their use in isolated cardiac dysfunction are lacking. Epidemiologic studies have documented increased risk of thrombus formation and stroke occurrence in patients with cardiomyopathy that is inversely related to ejection fraction. However, it remains at the clinician's discretion to determine at what degree of left ventricular dysfunction the potential benefits of stroke reduction outweigh the risks of undesirable bleeding with anticoagulation. This paper summarizes the pathophysiology of thrombus formation in heart failure patients; reviews previous studies and current recommendations for anticoagulation; provides a clinical rationale for anticoagulation when conclusive data are lacking; and discusses ongoing clinical trials designed to clarify these issues.     

Comprehensive in‐hospital monitoring in acute heart failure: applications for clinical practice and future directions for research. A statement from the Acute Heart Failure Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)

This paper provides a practical clinical application of guideline recommendations relating to the inpatient monitoring of patients with acute heart failure, through the evaluation of various clinical, biomarker, imaging, invasive and non‐invasive approaches. Comprehensive inpatient monitoring is crucial to the optimal management of acute heart failure patients. The European Society of Cardiology heart failure guidelines provide recommendations for the inpatient monitoring of acute heart failure, but the level of evidence underpinning most recommendations is limited. Many tools are available for the in‐hospital monitoring of patients with acute heart failure, and each plays a role at various points throughout the patient's treatment course, including the emergency department, intensive care or coronary care unit, and the general ward. Clinical judgment is the preeminent factor guiding application of inpatient monitoring tools, as the various techniques have different patient population targets. When applied appropriately, these techniques enable decision making. However, there is limited evidence demonstrating that implementation of these tools improves patient outcome. Research priorities are identified to address these gaps in evidence. Future research initiatives should aim to identify the optimal in‐hospital monitoring strategies that decrease morbidity and prolong survival in patients with acute heart failure.     

Current status of implantable cardioverter-defibrillator therapy in heart failure

Sudden cardiac arrest is one of the leading causes of death in patients with heart failure (HF). The implantable cardioverter-defibrillator (ICD) is the only evidence-based treatment strategy for patients who have survived a life-threatening ventricular arrhythmic event. Randomized clinical trials have shown that specific subsets of HF patients with ischemic and nonischemic dilated cardiomyopathy benefit from ICD therapy for primary prevention of sudden cardiac arrest. Cardiac resynchronization therapy has become the device-based therapy of choice for improving symptoms and survival in severe HF patients with evidence of ventricular dyssynchrony. This review summarizes the current status of ICD therapy in treating HF patients based on randomized clinical trials and current practice guidelines.     

Statin therapy in heart failure: prognostic effects and potential mechanisms

The use of statins as therapy for heart failure remains controversial. Nevertheless, many of the pleiotropic effects of statins are potentially applicable in heart failure. Although early statin trials excluded patients with heart failure because of concerns that lowering serum cholesterol could worsen an already poor prognosis, statin treatment has not been shown to have adverse effects on either cardiovascular events or mortality, and recent experimental and clinical studies have shown promise of benefit. Two large, ongoing trials should provide definitive evidence of the value of statin therapy for patients with heart failure. Pending those results, it is reasonable to follow current National Cholesterol Education Program guidelines in this high-risk population.     

NT-proBNP and BNP: biomarkers for heart failure management

Guidelines for the pharmacological treatment of heart failure (HF) are based on results from large clinical trials demonstrating benefit. State of the art pharmacological management of HF assumes that target doses should be the same as those used in trials. Thus equal doses are recommended for all in practical guidelines, but this strategy might not fit individual needs. NT-proBNP and BNP emerged as potential biomarkers of clinical interest in HF management. NT-proBNP and BNP are related to HF severity and to clinical status. NT-proBNP and BNP are strongly associated with prognosis across the whole spectrum of HF patients. A pilot study has shown that NT-proBNP-guided therapy is associated with improved outcome in HF. Although at present there are still few data to make firm recommendations on the use of NT-proBNP or BNP levels as biomarkers for HF management, future studies will provide further insight on this issue.     

Primer: practical approach to the selection of patients for and application of EECP

Over the past decade, the frequency of use of enhanced external counterpulsation (EECP) has increased in patients with angina, irrespective of medical therapy and coronary revascularization status. Many patients referred for EECP have one or more comorbidities that could affect this treatment's efficacy, safety, or both. By use of data from more than 8,000 patients enrolled in the International EECP Patient Registry, we provide practical guidelines for the selection and treatment of patients. We have focused on considerations for patients who have one or more of the following characteristics: age older than 75 years, diabetes, obesity, heart failure, and peripheral vascular disease. We have also reviewed outcomes and treatment recommendations for individuals with poor diastolic augmentation during treatment, for those with atrial fibrillation or pacemakers, and for those receiving anticoagulation therapy. Lastly, we examined relevant data regarding extended courses of EECP, repeat therapy, or both. While clinical studies have demonstrated the usefulness of EECP in selected patients, these guidelines permit recommendations for the extended application of this important treatment to subsets of patients excluded from clinical trials.     

2022 ACC/AHA/HFSA Guideline for the Management of Heart Failure: Executive Summary

BackgroundThe 2022 American College of Cardiology/American Heart Association/Heart Failure Society of America (AHA/ACC/HFSA) Guideline for the Management of Heart Failure replaces the 2013 ACCF/AHA Guideline for the Management of Heart Failure and the 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure. The 2022 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose and manage patients with heart failure.MethodsA comprehensive literature search was conducted from May 2020 to December 2020, encompassing studies, reviews and other evidence conducted in human subjects that were published in English from MEDLINE (PubMed), EMBASE, the Cochrane Collaboration, the Agency for Healthcare Research and Quality, and other relevant databases. Additional relevant clinical trials and research studies published through September 2021 were also considered. This guideline was harmonized with other American Heart Association/American College of Cardiology guidelines published through December 2021.Results and ConclusionsHeart failure remains a leading cause of morbidity and mortality globally. The 2022 heart failure guideline provides recommendations based on contemporary evidence for the treatment of these patients. The recommendations present an evidence-based approach to managing patients with heart failure, with the intent to improve quality of care and align with patients’ interests. Many recommendations from the earlier heart failure guidelines have been updated with new evidence, and new recommendations have been created when supported by published data. Value statements are provided for certain treatments that have high-quality published economic analyses.     

2022 ACC/AHA/HFSA Guideline for the Management of Heart Failure

AimThe “2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure” replaces the “2013 ACCF/AHA Guideline for the Management of Heart Failure” and the “2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure.” The 2022 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with heart failure.MethodsA comprehensive literature search was conducted from May 2020 to December 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (PubMed), EMBASE, the Cochrane Collaboration, the Agency for Healthcare Research and Quality, and other relevant databases. Additional relevant clinical trials and research studies, published through September 2021, were also considered. This guideline was harmonized with other American Heart Association/American College of Cardiology guidelines published through December 2021.StructureHeart failure remains a leading cause of morbidity and mortality globally. The 2022 heart failure guideline provides recommendations based on contemporary evidence for the treatment of these patients. The recommendations present an evidence-based approach to managing patients with heart failure, with the intent to improve quality of care and align with patients’ interests. Many recommendations from the earlier heart failure guidelines have been updated with new evidence, and new recommendations have been created when supported by published data. Value statements are provided for certain treatments with high-quality published economic analyses.     

Whom Should I Refer in 2014 for Cardiac Resynchronization?

Heart failure continues to be a significant source of morbidity and mortality amongst Canadians. Many patients remain symptomatic despite guideline-directed medical therapy. For drug-refractory patients with dyssynchronous systolic heart failure, cardiac resynchronization therapy (CRT) has reliably reduced heart failure hospitalizations and related deaths. Unfortunately, despite significant advancements in technology and our understanding of its clinical effect, the CRT nonresponder rate remains approximately 30%. Great efforts have been invested into identifying clinical predictors of CRT response. Left bundle branch block conduction delay and wider QRS (> 150 ms) have consistently been associated with clinical response to CRT, earning them the strongest recommendations in the revised guidelines in Canada and across the world. Due in large part to the benefit observed in the Resynchronization-Defibrillation for Ambulatory Heart Failure Trial (RAFT) trial, patients with mild heart failure symptoms (New York Heart Association class II) are now also candidates for resynchronization therapy. Patients with atrial fibrillation, non-left bundle branch block conduction patterns, and chronic right ventricular pacing have historically been associated with poor response. However, these populations remain grossly underrepresented in the large trials. In the absence of more data, these patients continue to receive weaker recommendations for CRT in the guidelines.     

Heart failure and non-ST-segment elevation myocardial infarction: a review for a widespread situation

Up to 15% of patients with NSTEMI present at admission with heart failure. Scientific evidence for its management is limited but much progress has been made during the last years. Our purpose was to review the last data concerning heart failure in NSTEMI and perform an update on the subject, with the following findings as main highlights. As Killip classes III and IV, Killip class II onset in the context of NSTEMI has also proven bad prognosis significance. Beta-blocker therapy has proven benefit to patients with Killip class II in observational studies and small trials. Angiotensin-converting enzyme inhibitor therapy shows stronger evidence of benefit in patients with heart failure than in patients without it. Eplerenone is indicated for patients with left ventricular dysfunction and heart failure or diabetes mellitus. Implantable cardioverter defibrillators improve survival in patients with severe ventricular dysfunction after a myocardial infarction. Cardiac resynchronization therapy indications must be carefully assessed due to the high rate of implants that do not fulfill guidelines indications. In conclusion, heart failure during a NSTEMI is a common and meaningful situation which warrants careful management and further investigation to reach stronger evidence for clinical recommendations.     

Chronic heart failure: improvement of the prognosis by therapy?

There are two goals in the management of chronic heart failure: relief of symptoms and prolongation of life. Until recently, pharmacological interventions were tested primarily in order to evaluate their effects on exercise capacity and clinical symptoms. However, two multicenter trials have now provided evidence that treatment of chronic heart failure is able to improve mortality. Indeed, prolongation of life without improving symptoms is not desirable. The two classic keystones of therapy in heart failure, diuretics and digitalis, remain powerful agents to relieve symptoms. However, their impact on survival remains elusive, since no controlled studies are available which address this question with adequate sample size. Vasodilators such as the combination of hydralazine and isosorbide dinitrate and ACE-inhibitors, however, have been shown to improve survival in patients with moderate to severe chronic heart failure. In contrast, prazosin failed to be effective in this respect. More sophisticated questions emerge, in particular, do ACE-inhibitors or vasodilators, effectively interfere with the progression of the disease? May early treatment be preventive and retard the course of heart failure? Several large scale multicenter trials are now under way to address these issues.     

Treatment of chronic heart failure in long-term care facilities: implications of recent heart failure guidelines recommendations

Use of angiotensin-converting enzyme inhibitor in heart failure with left ventricular systolic dysfunction has revolutionized management of heart failure and resulted in several national heart failure guidelines. However, studies have documented underutilization of these life saving drugs. Subsequently, results of other randomized clinical trials revealed the beneficial effects of angiotensin receptor blockers, beta-blockers, and spironolactone in heart failure with systolic dysfunction, which prompted several other guidelines. However, all these guidelines were primarily restricted to systolic dysfunction. Heart failure is as much a geriatric syndrome as it is a cardiac. Most heart failure patients are older adults. About half of the heart failure in older adults is not associated with left ventricular systolic dysfunction. Two recent heart failure guidelines, from the European Society of Cardiology and the American College of Cardiology/American Heart Association, published respectively in September and December 2001 included recommendations for patients with preserved left ventricular systolic function and other special populations, including older adults and those at end of life. The purpose of this article is to review the relevance of these two guidelines to heart failure patients living in long-term care facilities. As our population is aging, more heart failure patients are expected to live in long-term care facilities. Appropriate evaluation and management of these patients are essential to improve quality of heart failure care in the coming decades.     

Which drug for what patient with heart failure, and when?

Congestive heart failure is emerging as an important public health problem because of its frequency and high mortality. Over the past decade, a number of clinical trials have been launched in a systematic attempt to determine an optimal therapeutic strategy for the treatment of heart failure. There appears to be a trend to begin treatment with both a diuretic and a vasodilator regimen in patients with symptomatic left ventricular dysfunction. Converting enzyme inhibitors have been shown to clearly benefit patients with class IV heart failure. The role of digitalis, other inotropic agents, beta-blockers, partial beta-agonists and antiarrhythmic agents is still evolving, but several clinical trials of these agents have been recently launched or are in the planning stages. Patients with symptomless left ventricular dysfunction are at risk to develop heart failure. One attractive hypothesis being tested is that preventive therapy with converting enzyme inhibitors may prevent progressive cardiac dilatation and thereby improve survival in this important reservoir of patients. Until the results of these numerous clinical trials are published, physicians should reserve judgement regarding the undefined efficacy of various investigational agents used in the treatment of heart failure and use their experience and judgement when planning a therapeutic strategy for their individual patients.     

Prophylactic cardioverter defibrillator utilization in the "real world": a conundrum

Randomized controlled trials have shown that implantable cardioverter defibrillator (ICD) therapy improves survival in appropriately selected patients with left ventricular dysfunction due to myocardial infarction (MI). Specific recommendations for ICD therapy have been included in consensus guidelines. There is, however, uncertainty as to whether guidelines on prophylactic ICD therapy are being applied in "real world" clinical practice. A report from a tertiary care center in Israel shows that in the period between 2005 and 2009, a prophylactic ICD was implanted in only 14% of post-MI patients in whom it was indicated, according to current guidelines. Importantly, failure to systematically reassess left ventricular function after a MI was linked to underuse of ICDs. Various factors such as differential coverage by health care insurances, patients' decision, physician's evaluation of co-morbidities and age, as well as under-referral to specialized centers may be involved in limiting the use of prophylactic ICDs. The shortfall in ICD implant rate in relation to that expected from current guidelines calls for further integration of healthcare systems.     

Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology/Canadian Society of Cardiac Surgery Position Statement on Revascularization—Multivessel Coronary Artery Disease

This position statement addresses issues in revascularization for multivessel coronary artery disease (CAD) from the perspective of both cardiologists and cardiac surgeons. Recommendations are made based on evidence from clinical trials and observational studies, with an emphasis on the increasing number of individuals with significant comorbid disease burden and functional debilitation who are being referred for definitive management of their multivessel CAD in the context of routine clinical practice. These types of individuals have traditionally not been included in the many clinical trials that have been the basis for guidelines and recommendations, and the objective of the proposed medical intervention or revascularization (or both) would not necessarily be to improve prognosis but to improve quality of life. One purpose of this document is to propose practical multidisciplinary approaches to the management of these patients. Recommendations are made for revascularization in acute coronary syndromes and stable CAD, with specific considerations for individuals with left ventricular dysfunction and heart failure, chronic renal failure, and chronic obstructive pulmonary disease. We also consider the use of various risk scores, including the Society of Thoracic Surgeons score, the EuroSCORE, and the SYNTAX II score. The importance of a heart team approach is also emphasized. The complementary role of coronary bypass surgery and percutaneous coronary intervention is highlighted, along with the importance of optimal medical therapy.     

Toward Sex-Specific Guidelines for Cardiac Resynchronization Therapy?

An important treatment for patients with heart failure is cardiac resynchronization therapy (CRT). Even though only 20 % of women were included in clinical trials for CRT, a benefit has been shown in recent studies for subgroups of women compared to their male counterparts. Given this low inclusion rate of women in clinical studies, professional society guideline-based CRT recommendations, such as those by the American College of Cardiology Foundation (ACCF)/American Heart Association (AHA)/Heart Rhythm Society (HRS), may not truly represent the best treatment for women, especially since most of the reports that showed this greater benefit in women were published after the latest guidelines. Despite having research and multiple publications regarding sex-specific heart failure outcomes and response to CRT, the ACCF/AHA/HRS guidelines have not yet been updated to account for the recent information regarding the differences in benefit for women and men with similar patient characteristics. This review discusses the physiology behind CRT, sex-specific characteristics of heart failure, and cardiac electrophysiology and summarizes the current sex-specific literature to encourage consideration of CRT guidelines for women and men separately.     

Inotropic therapy of the failing myocardium

The clinical syndrome of congestive heart failure remains a therapeutic dilemma and challenge for the physician in 1992. This is a disease process that appears to be increasing in frequency and continues to carry an unacceptably high mortality rate. For years it has been well recognized that the combination of digoxin, Lasix and vasodilator therapy improved symptoms in these patients and decreased hospitalization, but did not increase survival. It was not until 1986 that the combination of digoxin, Lasix, Isordil, and hydralazine was shown to increase survival. Further significant improvement in quality of life and survival has recently been established in three large clinical trials, and it is now safe to say that the standard of care for symptomatic congestive heart failure in 1992 is digoxin, furosemide, and an ACE inhibitor, with the survival trials favoring the ACE inhibitor enalapril. The IV inotropic drug dobutamine remains the mainstay of pharmacological therapy for the treatment of severely refractory heart failure. Unfortunately, the phosphodiesterase inhibitors—amrinone, milrinone, and enoximone—have demonstrated unacceptable clinical side effects and have been withdrawn from further clinical study. In spite of these promising developments, the mortality and morbidity of congestive heart failure remains unacceptably high, and continued investigation in the new fields of pharmacology and the pathophysiology of congestive heart failure still must be aggressively pursued.     

What can post market registries tell us about the use of cardiac resynchronization therapy?

Cardiac resynchronization therapy (CRT) has become an established therapeutic option for patients with dilated cardiomyopathies and New York Heart Association class III congestive heart failure symptoms who also have a widened QRS complex on their electrocardiograms (generally > 120 ms). Results from a number of clinical trials have shown that CRT improves patients' exercise tolerance, quality of life, and survival. There is further evidence that CRT has structural effects on the heart with improved cardiac function. Despite these salutary results, clinical trials in CRT study prespecified populations that fit the inclusion criteria for these trials. Many patients have been excluded from these clinical trials and yet may potentially benefit from CRT. Evaluation of the effects of CRT on these populations might reveal the potential to expand the use of this therapy in larger numbers of patients to CRT who may not have been included in the clinical trial. This review article will assess the limitations of some of the clinical trials in CRT and will discuss the potential for CRT registries that are presently underway to extend the patient population that may benefit from this therapeutic option.     

Management of the patient with congestive heart failure using outpatient, home, and palliative care

Congestive heart failure is a chronic, debilitating illness, with increasing prevalence in the elderly. It is one of the most common causes for hospital admission, and associated treatment costs are estimated at $20.2 billion. Despite improved survival with medical therapy, beneficial effects on quality of life have not been consistently reported. In addition, optimum medical therapy, as recommended by evidence-based guidelines, are not always implemented. Counseling and education involving dietary modifications, activity recommendations, medication management, self-monitoring, prognosis, coping skills, social support, caregiver stress, and spiritual needs are critical components in the management of heart failure through initial diagnosis to end of life. Within the last decade, close follow-up for congestive heart failure has been associated with decreased hospitalizations, reduced hospital length of stay, improved functional status, better compliance, lower costs, and improved survival. Research trials have mainly been observational and small, and they have used different interventions. Little has been written regarding outpatient management of the patient with advanced congestive heart failure, and none of the current published guidelines addresses recommendations for the New York Heart Association class IV (other than for transplant candidacy). New models of close follow-up for chronic and advanced congestive heart failure should be investigated. These models could be implemented in urban and rural settings and be supported by private insurance or Medicare.