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Clinical manifestations and diagnosis of advanced heart failure

Wilson S Colucci, MD
Shannon M Dunlay, MD, MS
Section Editor
Donna Mancini, MD
Deputy Editor
Susan B Yeon, MD, JD, FACC


Advanced heart failure (HF) occurs when patients with HF experience persistent severe symptoms that interfere with daily life despite maximum evidence-based medical therapy. Patients with advanced HF have alternatively been described as having "refractory," "end-stage," or "American College of Cardiology/American Heart Association stage D" HF [1]. (See "Determining the etiology and severity of heart failure or cardiomyopathy", section on 'Stages in the development of HF'.)

An overview of the clinical manifestations and diagnosis of advanced HF will be presented here. The management of advanced HF, diagnosis and management of patients with suspected HF, and management of acute decompensated HF will be discussed separately. (See "Management of refractory heart failure with reduced ejection fraction" and "Overview of the therapy of heart failure with reduced ejection fraction" and "Treatment of acute decompensated heart failure: Components of therapy" and "Treatment of acute decompensated heart failure: General considerations" and "Epidemiology and causes of heart failure".)


Symptoms and signs — While signs and symptoms of advanced HF are variable, common manifestations of advanced HF include exercise intolerance, unintentional weight loss, refractory volume overload, as well as hypotension and signs of inadequate perfusion (eg, low pulse pressure). These signs and symptoms occur on maximum evidence-based medical therapy, following insertion of all appropriate devices (eg, cardiac synchronization therapy) and with all reversible causes of HF addressed. These patients frequently experience recurrent hospitalizations.

Mortality risk increases with each subsequent HF hospitalization [2,3]. The presence of repeated hospitalizations (≥2 in six months) or complicated hospitalizations (eg, requiring intensive care unit care or inotropes) can suggest advanced HF.

Dyspnea, fatigue, and exercise intolerance — As HF progresses, patients frequently develop symptoms such as dyspnea, lightheadedness, or fatigue at rest or with minimal exertion that limits exercise capacity. Patients with advanced HF generally exhibit New York Heart Association (NYHA) functional class III (symptoms with minimal exertion) or IV (symptoms at rest or with any activity) symptoms (table 1). Since normal exercise capacity varies based on individual factors, such as age and activity level, standard benchmarks for exercise capacity may not be suitable for individual patients. Thus, a patient’s report of decline in exercise capacity over time can be most informative in signaling a significant change in exercise capacity. However, exercise limitation that is worrisome for advanced HF includes inability to walk a city block or perform activities of daily living such as bathing or dressing without limiting symptoms [1]. Many patients will progress to have dyspnea at rest, including at night (orthopnea, paroxysmal nocturnal dyspnea). Poor functional status is an adverse prognostic indicator in patients with HF. (See "Predictors of survival in heart failure with reduced ejection fraction".)

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Literature review current through: Oct 2017. | This topic last updated: Jun 14, 2017.
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  1. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 2013; 128:1810.
  2. Solomon SD, Dobson J, Pocock S, et al. Influence of nonfatal hospitalization for heart failure on subsequent mortality in patients with chronic heart failure. Circulation 2007; 116:1482.
  3. Setoguchi S, Stevenson LW, Schneeweiss S. Repeated hospitalizations predict mortality in the community population with heart failure. Am Heart J 2007; 154:260.
  4. Anker SD, Sharma R. The syndrome of cardiac cachexia. Int J Cardiol 2002; 85:51.
  5. Lee DS, Austin PC, Rouleau JL, et al. Predicting mortality among patients hospitalized for heart failure: derivation and validation of a clinical model. JAMA 2003; 290:2581.
  6. Fonarow GC, Adams KF Jr, Abraham WT, et al. Risk stratification for in-hospital mortality in acutely decompensated heart failure: classification and regression tree analysis. JAMA 2005; 293:572.
  7. Pocock SJ, Ariti CA, McMurray JJ, et al. Predicting survival in heart failure: a risk score based on 39 372 patients from 30 studies. Eur Heart J 2013; 34:1404.
  8. Allen LA, Gheorghiade M, Reid KJ, et al. Identifying patients hospitalized with heart failure at risk for unfavorable future quality of life. Circ Cardiovasc Qual Outcomes 2011; 4:389.
  9. Kittleson M, Hurwitz S, Shah MR, et al. Development of circulatory-renal limitations to angiotensin-converting enzyme inhibitors identifies patients with severe heart failure and early mortality. J Am Coll Cardiol 2003; 41:2029.
  10. Filippatos G, Rossi J, Lloyd-Jones DM, et al. Prognostic value of blood urea nitrogen in patients hospitalized with worsening heart failure: insights from the Acute and Chronic Therapeutic Impact of a Vasopressin Antagonist in Chronic Heart Failure (ACTIV in CHF) study. J Card Fail 2007; 13:360.
  11. Zamora E, Lupón J, Vila J, et al. Estimated glomerular filtration rate and prognosis in heart failure: value of the Modification of Diet in Renal Disease Study-4, chronic kidney disease epidemiology collaboration, and cockroft-gault formulas. J Am Coll Cardiol 2012; 59:1709.
  12. McAlister FA, Ezekowitz J, Tarantini L, et al. Renal dysfunction in patients with heart failure with preserved versus reduced ejection fraction: impact of the new Chronic Kidney Disease-Epidemiology Collaboration Group formula. Circ Heart Fail 2012; 5:309.
  13. Klein L, Massie BM, Leimberger JD, et al. Admission or changes in renal function during hospitalization for worsening heart failure predict postdischarge survival: results from the Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF). Circ Heart Fail 2008; 1:25.
  14. Damman K, Navis G, Voors AA, et al. Worsening renal function and prognosis in heart failure: systematic review and meta-analysis. J Card Fail 2007; 13:599.
  15. Horwich TB, Kalantar-Zadeh K, MacLellan RW, Fonarow GC. Albumin levels predict survival in patients with systolic heart failure. Am Heart J 2008; 155:883.
  16. Uthamalingam S, Kandala J, Daley M, et al. Serum albumin and mortality in acutely decompensated heart failure. Am Heart J 2010; 160:1149.
  17. Arques S, Ambrosi P. Human serum albumin in the clinical syndrome of heart failure. J Card Fail 2011; 17:451.
  18. Allen LA, Felker GM, Pocock S, et al. Liver function abnormalities and outcome in patients with chronic heart failure: data from the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program. Eur J Heart Fail 2009; 11:170.
  19. Metra M, Ponikowski P, Dickstein K, et al. Advanced chronic heart failure: A position statement from the Study Group on Advanced Heart Failure of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 2007; 9:684.
  20. Breathett K, Allen LA, Udelson J, et al. Changes in Left Ventricular Ejection Fraction Predict Survival and Hospitalization in Heart Failure With Reduced Ejection Fraction. Circ Heart Fail 2016; 9.
  21. Solomon SD, Anavekar N, Skali H, et al. Influence of ejection fraction on cardiovascular outcomes in a broad spectrum of heart failure patients. Circulation 2005; 112:3738.
  22. Kjaergaard J, Akkan D, Iversen KK, et al. Right ventricular dysfunction as an independent predictor of short- and long-term mortality in patients with heart failure. Eur J Heart Fail 2007; 9:610.
  23. Meyer P, Filippatos GS, Ahmed MI, et al. Effects of right ventricular ejection fraction on outcomes in chronic systolic heart failure. Circulation 2010; 121:252.
  24. Mohammed SF, Hussain I, AbouEzzeddine OF, et al. Right ventricular function in heart failure with preserved ejection fraction: a community-based study. Circulation 2014; 130:2310.
  25. Temporelli PL, Scapellato F, Eleuteri E, et al. Doppler echocardiography in advanced systolic heart failure: a noninvasive alternative to Swan-Ganz catheter. Circ Heart Fail 2010; 3:387.
  26. Mehra MR, Kobashigawa J, Starling R, et al. Listing criteria for heart transplantation: International Society for Heart and Lung Transplantation guidelines for the care of cardiac transplant candidates--2006. J Heart Lung Transplant 2006; 25:1024.
  27. Arslan S, Erol MK, Gundogdu F, et al. Prognostic value of 6-minute walk test in stable outpatients with heart failure. Tex Heart Inst J 2007; 34:166.
  28. Guazzi M, Dickstein K, Vicenzi M, Arena R. Six-minute walk test and cardiopulmonary exercise testing in patients with chronic heart failure: a comparative analysis on clinical and prognostic insights. Circ Heart Fail 2009; 2:549.
  29. Klein I, Danzi S. Thyroid disease and the heart. Circulation 2007; 116:1725.
  30. Iversen KK, Kjaergaard J, Akkan D, et al. Chronic obstructive pulmonary disease in patients admitted with heart failure. J Intern Med 2008; 264:361.
  31. Mascarenhas J, Lourenço P, Lopes R, et al. Chronic obstructive pulmonary disease in heart failure. Prevalence, therapeutic and prognostic implications. Am Heart J 2008; 155:521.
  32. Minasian AG, van den Elshout FJ, Dekhuijzen PN, et al. COPD in chronic heart failure: less common than previously thought? Heart Lung 2013; 42:365.