- •
Heart failure (HF) is a progressive, clinical syndrome hallmarked by the inability of the heart to efficiently fill or provide systemic blood flow, resulting in symptoms of fatigue, dyspnea, and ultimately, significant morbidity and mortality.
- •
Current guidelines support the use of HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction to replace systolic HF and diastolic HF, respectively.
- •
Although neurohormonal and sympathetic inhibition form the foundation of HFrEF
Understanding Heart Failure
Section snippets
Key points
Pathophysiology
The syndrome of HF develops from an index event that results in ventricular dysfunction and ultimately HF symptoms. The index event, depending on cause, can be abrupt in onset (ie, myocardial infarction [MI], viral myocarditis) or may be gradual and develop over time (ie, left ventricular [LV] hypertrophy, genetic).4 This index event results in compensatory mechanisms that at first serve to maintain adequate cardiac output in the face of LV dysfunction. Over time, however, salt and water
Cause of heart failure
HF often develops from intrinsic myocardial structural or functional abnormalities. This dysfunction, first termed cardiomyopathy in 1957, can result from a myriad of causes; many remain unknown.16 Clinically, the initial distinction in categorizing a cardiomyopathy, specifically in the setting of HFrEF, is to identify whether the myocardial dysfunction is associated with coronary artery disease (CAD). CAD can be assessed by either invasive or noninvasive means.2, 3, 17, 18 Treatment of
Current approach to heart failure staging
First described in 1928, the New York Heart Association (NYHA) functional classification remains a commonly used system to describe functional capacity in HF.2, 39 As described in Table 2, this system subjectively assesses disease-related symptoms and exercise capacity and stratifies patients into 4 categories ranging from lack of symptoms with ordinary activity (class I) to the inability to perform any physical activity without symptoms and with symptoms at rest (class IV).2 Although this
Current approach to heart failure treatment
Beyond those with stage A HF, in which the current approach is largely control of modifiable risk factors (for CAD, diabetes, hypertension, and other risk factors), a remarkable evidence base has amassed over the last 3 decades informing the approach to the treatment of stage B HF and beyond (Fig. 4, Fig. 5, Fig. 6, Table 3). As evident from Fig. 4, Fig. 5, Fig. 6, treatment recommendations for chronic HFrEF are largely uniform across the American and European guidelines, although differences
Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers
Beginning in the 1980s, and continuing for the better part of a decade, several clinical trials emerged solidifying the beneficial effects of angiotensin-converting enzyme inhibitors (ACEI) in the improvement of mortality as well as symptoms, hemodynamics, and ventricular dysfunction seen in HFrEF (see Table 3).41, 42, 43, 44 The aggregate of these trials reveal an ∼25% reduction in mortality in those treated with ACEI as compared with controls.45 Furthermore, ACEI therapy has been shown to be
Implantable Cardioverter-Defibrillators
Patients with HFrEF are at increased risk for ventricular arrhythmias and sudden cardiac death (SCD). For this reason, over the last 20 years, ICDs have been studied for both primary and secondary prevention in the setting of ICM and NICM across several clinical trials and have emerged as extremely effective in reducing SCD in these populations.2, 72, 73, 74, 75, 76
The Multicenter Automatic Defibrillator Implantation Trial (MADIT) was the first to show a mortality benefit of ICD therapy as
Advanced therapies
It is estimated that 5% of patients with HF have end-stage, or stage D disease, carrying 1- and 5-year mortality rates of 28% and 80%, respectively.105 These patients are characterized by features of worsening symptoms, objective evidence of reduced exercise capacity, fluid retention, recent HF admissions, biomarker and echocardiographic evidence of severe cardiac dysfunction, as well as inability to tolerate standard HF therapy.106, 107 These signs and symptoms should prompt the clinician to
Biomarker assessment in heart failure
There has been significant growth in the identification and understanding of biomarkers and their role in the diagnosis, management, and prognostication of HF.114, 115, 116 Such molecules, most notably B-type natriuretic peptide (BNP) or NT-proBNP, have been shown to be prognostically powerful, although their role in optimizing HF management and improving survival and readmission rates has been less clear.
The future
The publication of the Angiotensin-Neprilysin Inhibition versus Enalapril in HF (PARADIGM-HF) trial, evaluating combined ARB/Neprilysin-inhibition (LCZ696) as compared with enalapril alone in HFrEF patients may be seen as representative of a new era of HF therapeutic discovery.117 The new drug resulted in an additional 18% relative risk reduction in the combined primary endpoint (CV death or first HF hospitalization) over those treated with ACEI, with similar significant reductions in the
Summary
Despite significant advances in the understanding of the pathophysiology and treatment of HF over the last 3 decades, HF is a progressive condition with a rising prevalence, and the primary cause for hospitalization among the elderly. In addition to the current evidence-based treatment approaches, further study is required to improve the ability to identify, treat, and ultimately prevent this condition.
References (132)
- et al.
2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
J Am Coll Cardiol
(2013) - et al.
Noncardiac comorbidities in heart failure with reduced versus preserved ejection fraction
J Am Coll Cardiol
(2014) - et al.
Outcomes in world health organization group II pulmonary hypertension: mortality and readmission trends with systolic and preserved ejection fraction-induced pulmonary hypertension
J Card Fail
(2014) - et al.
Role of the renin-angiotensin-aldosterone system and proinflammatory mediators in cardiovascular disease
Am J Cardiol
(2006) - et al.
Effects of left ventricular volume overload on mitochondrial and death-receptor-mediated apoptotic pathways in the transition to heart failure
Am J Cardiol
(2009) - et al.
Etiology and pathophysiology of new-onset heart failure: evaluation by myocardial perfusion imaging
J Nucl Cardiol
(2009) - et al.
Update 2011: clinical and genetic issues in familial dilated cardiomyopathy
J Am Coll Cardiol
(2011) - et al.
Review and metaanalysis of the frequency of familial dilated cardiomyopathy
Am J Cardiol
(2011) - et al.
The MOGE(S) classification for a phenotype-genotype nomenclature of cardiomyopathy: endorsed by the World Heart Federation
J Am Coll Cardiol
(2013) - et al.
The MOGE(S) classification of cardiomyopathy for clinicians
J Am Coll Cardiol
(2014)
Asymptomatic cardiac toxicity in long-term cancer survivors: defining the population and recommendations for surveillance
Semin Oncol
Cardiotoxicity of chemotherapeutic agents and radiotherapy-related heart disease: ESMO clinical practice guidelines
Ann Oncol
Patterns of cardiac toxicity associated with irreversible proteasome inhibition in the treatment of multiple myeloma
J Card Fail
Diabetes mellitus, a predictor of morbidity and mortality in the studies of left ventricular dysfunction (SOLVD) trials and registry
Am J Cardiol
Obesity cardiomyopathy: pathophysiology and evolution of the clinical syndrome
Am J Med Sci
Myocardial lipid accumulation in patients with pressure-overloaded heart and metabolic syndrome
J Lipid Res
Myocardial lipid accumulation and lipotoxicity in heart failure
J Lipid Res
Evidence-based therapy for heart failure
Med Clin North Am
Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-alternative trial
Lancet
Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-added trial
Lancet
Relation of aldosterone “escape” despite angiotensin-converting enzyme inhibitor administration to impaired exercise capacity in chronic congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy
Am J Cardiol
Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the carvedilol or metoprolol european trial (COMET): randomised controlled trial
Lancet
Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study
Lancet
Effects on outcomes of heart rate reduction by ivabradine in patients with congestive heart failure: is there an influence of beta-blocker dose?: findings from the SHIFT (Systolic Heart Failure Treatment with the I(f) Inhibitor Ivabradine Trial) study
J Am Coll Cardiol
Racial differences in response to therapy for heart failure: analysis of the vasodilator-heart failure trials. Vasodilator-Heart Failure Trial Study Group
J Card Fail
The use of digoxin in patients with worsening chronic heart failure: reconsidering an old drug to reduce hospital admissions
J Am Coll Cardiol
Inappropriate implantable cardioverter-defibrillator shocks in MADIT II: frequency, mechanisms, predictors, and survival impact
J Am Coll Cardiol
Applicability of a risk score for prediction of the long-term (8-year) benefit of the implantable cardioverter-defibrillator
J Am Coll Cardiol
Implantable cardioverter-defibrillator prescription in the elderly
Heart Rhythm
Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms
J Am Coll Cardiol
Prevention of disease progression by cardiac resynchronization therapy in patients with asymptomatic or mildly symptomatic left ventricular dysfunction: insights from the European Cohort of the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) trial
J Am Coll Cardiol
Cardiac resynchronization therapy: past, present, and future
Heart Fail Clin
Forecasting the impact of heart failure in the united states: a policy statement from the American Heart Association
Circ Heart Fail
ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the task force for the diagnosis and treatment of acute and chronic heart failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC
Eur J Heart Fail
Mechanisms and models in heart failure: the biomechanical model and beyond
Circulation
Trends in prevalence and outcome of heart failure with preserved ejection fraction
N Engl J Med
Trends in patients hospitalized with heart failure and preserved left ventricular ejection fraction: prevalence, therapies, and outcomes
Circulation
Drug discovery for heart failure: a new era or the end of the pipeline?
Nat Rev Drug Discov
Relations of plasma matrix metalloproteinase-9 to clinical cardiovascular risk factors and echocardiographic left ventricular measures: the Framingham Heart Study
Circulation
Adrenergic effects on the biology of the adult mammalian cardiocyte
Circulation
Inflammatory and anti-inflammatory cytokines in chronic heart failure: potential therapeutic implications
Ann Med
Heart failure
N Engl J Med
Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention
Circulation
Non-invasive diagnosis of ischaemic heart failure using 64-slice computed tomography
Eur Heart J
Genetics of common forms of heart failure: challenges and potential solutions
Curr Opin Cardiol
Obesity and the risk of heart failure
N Engl J Med
The incidence of congestive heart failure in type 2 diabetes: an update
Diabetes Care
Antioxidative treatment prevents activation of death-receptor- and mitochondrion-dependent apoptosis in the hearts of diabetic rats
Diabetologia
Acute hyperglycemia attenuates endothelium-dependent vasodilation in humans in vivo
Circulation
Diabetic cardiomyopathy
Curr Hypertens Rep
Cited by (18)
Heart failure subphenotypes based on repeated biomarker measurements are associated with clinical characteristics and adverse events (Bio-SHiFT study)
2022, International Journal of CardiologyCitation Excerpt :More specific phenotyping may enable treatment strategies directed towards the different HF subphenotypes' mechanisms. Moreover, improved phenotyping may provide opportunities for more accurate prognostication by associating subphenotypes with the occurrence of clinical endpoints [14–16]. These prognostic insights may ultimately contribute to personalized monitoring and timing of treatment strategies.
Hyperkalemia as a limiting factor of neurohormonal blockade/modulation in everyday clinical practice
2022, Revista Portuguesa de CardiologiaCitation Excerpt :Heart failure (HF) is a growing public health concern that affects 26 million people worldwide.1 Its prevalence is predicted to increase by 25% in the next decade.2 HF is the main cause of hospitalizations >65 years of age in Europe and in the United States of America (USA).3
Peroxisome proliferator-activated receptors as therapeutic targets for heart failure
2017, Biomedicine and PharmacotherapyCitation Excerpt :Heart failure (HF) is a clinical syndrome in which the cardiac muscle cannot maintain adequate blood supply for tissue metabolism [1]. It affects approximately five-million adults in the United States and over 23 million individuals worldwide [2,3]. Its prevalence has increased recently due to the increasing number of patients surviving heart attacks [4].
For the improvement of Heart Failure treatment in Portugal ‐ Consensus statement
2017, Revista Portuguesa de CardiologiaCurrent experimental and early investigational agents for cardiac fibrosis: where are we at?
2024, Expert Opinion on Investigational Drugs
Disclosure Statement: No conflicts of interest.