Understanding Heart Failure

https://doi.org/10.1016/j.ccep.2015.08.001Get rights and content

Section snippets

Key points

  • 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

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.

First page preview

First page preview
Click to open first page preview

References (132)

  • J.R. Carver et al.

    Asymptomatic cardiac toxicity in long-term cancer survivors: defining the population and recommendations for surveillance

    Semin Oncol

    (2013)
  • D. Bovelli et al.

    Cardiotoxicity of chemotherapeutic agents and radiotherapy-related heart disease: ESMO clinical practice guidelines

    Ann Oncol

    (2010)
  • E.W. Grandin et al.

    Patterns of cardiac toxicity associated with irreversible proteasome inhibition in the treatment of multiple myeloma

    J Card Fail

    (2015)
  • D.M. Shindler et al.

    Diabetes mellitus, a predictor of morbidity and mortality in the studies of left ventricular dysfunction (SOLVD) trials and registry

    Am J Cardiol

    (1996)
  • M.A. Alpert

    Obesity cardiomyopathy: pathophysiology and evolution of the clinical syndrome

    Am J Med Sci

    (2001)
  • R. Marfella et al.

    Myocardial lipid accumulation in patients with pressure-overloaded heart and metabolic syndrome

    J Lipid Res

    (2009)
  • P.C. Schulze

    Myocardial lipid accumulation and lipotoxicity in heart failure

    J Lipid Res

    (2009)
  • P.C. Deedwania et al.

    Evidence-based therapy for heart failure

    Med Clin North Am

    (2012)
  • C.B. Granger et al.

    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

    (2003)
  • J.J. McMurray et al.

    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

    (2003)
  • M. Cicoira et al.

    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

    (2002)
  • P.A. Poole-Wilson et al.

    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

    (2003)
  • K. Swedberg et al.

    Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study

    Lancet

    (2010)
  • K. Swedberg et al.

    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

    (2012)
  • P. Carson et al.

    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

    (1999)
  • A.P. Ambrosy et al.

    The use of digoxin in patients with worsening chronic heart failure: reconsidering an old drug to reduce hospital admissions

    J Am Coll Cardiol

    (2014)
  • J.P. Daubert et al.

    Inappropriate implantable cardioverter-defibrillator shocks in MADIT II: frequency, mechanisms, predictors, and survival impact

    J Am Coll Cardiol

    (2008)
  • A. Barsheshet et al.

    Applicability of a risk score for prediction of the long-term (8-year) benefit of the implantable cardioverter-defibrillator

    J Am Coll Cardiol

    (2012)
  • A.E. Epstein et al.

    Implantable cardioverter-defibrillator prescription in the elderly

    Heart Rhythm

    (2009)
  • C. Linde et al.

    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

    (2008)
  • C. Daubert et al.

    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

    (2009)
  • N.A. Chatterjee et al.

    Cardiac resynchronization therapy: past, present, and future

    Heart Fail Clin

    (2015)
  • P.A. Heidenreich et al.

    Forecasting the impact of heart failure in the united states: a policy statement from the American Heart Association

    Circ Heart Fail

    (2013)
  • J.J. McMurray et al.

    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

    (2012)
  • D.L. Mann et al.

    Mechanisms and models in heart failure: the biomechanical model and beyond

    Circulation

    (2005)
  • T.E. Owan et al.

    Trends in prevalence and outcome of heart failure with preserved ejection fraction

    N Engl J Med

    (2006)
  • B.A. Steinberg et al.

    Trends in patients hospitalized with heart failure and preserved left ventricular ejection fraction: prevalence, therapies, and outcomes

    Circulation

    (2012)
  • D.M. Kaye et al.

    Drug discovery for heart failure: a new era or the end of the pipeline?

    Nat Rev Drug Discov

    (2007)
  • J. Sundstrom et al.

    Relations of plasma matrix metalloproteinase-9 to clinical cardiovascular risk factors and echocardiographic left ventricular measures: the Framingham Heart Study

    Circulation

    (2004)
  • D.L. Mann et al.

    Adrenergic effects on the biology of the adult mammalian cardiocyte

    Circulation

    (1992)
  • P. Aukrust et al.

    Inflammatory and anti-inflammatory cytokines in chronic heart failure: potential therapeutic implications

    Ann Med

    (2005)
  • M. Jessup et al.

    Heart failure

    N Engl J Med

    (2003)
  • B.J. Maron et al.

    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

    (2006)
  • S. Ghostine et al.

    Non-invasive diagnosis of ischaemic heart failure using 64-slice computed tomography

    Eur Heart J

    (2008)
  • C.D. Rau et al.

    Genetics of common forms of heart failure: challenges and potential solutions

    Curr Opin Cardiol

    (2015)
  • S. Kenchaiah et al.

    Obesity and the risk of heart failure

    N Engl J Med

    (2002)
  • G.A. Nichols et al.

    The incidence of congestive heart failure in type 2 diabetes: an update

    Diabetes Care

    (2004)
  • J. Bojunga et al.

    Antioxidative treatment prevents activation of death-receptor- and mitochondrion-dependent apoptosis in the hearts of diabetic rats

    Diabetologia

    (2004)
  • S.B. Williams et al.

    Acute hyperglycemia attenuates endothelium-dependent vasodilation in humans in vivo

    Circulation

    (1998)
  • A.A. Karnik et al.

    Diabetic cardiomyopathy

    Curr Hypertens Rep

    (2007)
  • 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 Cardiology
      Citation 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 Cardiologia
      Citation 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 Pharmacotherapy
      Citation 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].

    View all citing articles on Scopus

    Disclosure Statement: No conflicts of interest.

    View full text