Abstract
Heart failure with preserved ejection fraction (HFpEF) is a common clinical syndrome associated with high rates of morbidity and mortality. Due to the lack of evidence-based therapies and increasing prevalence of HFpEF, clinicians are often confronted with these patients and yet have little guidance on how to effectively diagnose and manage them. Here we offer 10 key lessons to assist with the care of patients with HFpEF: (1) Know the difference between diastolic dysfunction, diastolic heart failure, and HFpEF; (2) diagnosing HFpEF is challenging, so be thorough and consider invasive hemodynamic testing to confirm the diagnosis; (3) a normal B-type natriuretic peptide does not exclude the diagnosis of HFpEF; (4) elevated pulmonary artery systolic pressure on echocardiography in the presence of a normal ejection fraction should prompt consideration of HFpEF; (5) use dynamic testing in evaluating the possibility of HFpEF in patients with unexplained dyspnea or exercise tolerance; (6) all patients with HFpEF should be systematically evaluated for the presence of coronary artery disease; (7) use targeted treatment for HFpEF patients based on their phenotypic classification; (8) treat HFpEF patients now by treating their comorbidities; (9) understand the importance of heart rate in HFpEF— lower is not always better; and (10) do not forget to consider rare diseases (“zebras”) as causes for HFpEF when evaluating and treating patients. Taken together, these 10 key lessons can help clinicians care for challenging patients with HFpEF while we eagerly await the results of ongoing HFpEF clinical trials and observational studies.
Keywords: B-type natriuretic peptide, comorbidities, diagnosis, diastolic heart failure, exercise testing, pulmonary hypertension, treatment.
Graphical Abstract
[1]
Lam CS, Donal E, Kraigher-Krainer E, Vasan RS. Epidemiology and clinical course of heart failure with preserved ejection fraction. Eur J Heart Fail 2011; 13: 18-28.
[2]
Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med 2006; 355: 251-9.
[3]
Shah SJ, Heitner JF, Sweitzer NK, et al. Baseline characteristics of Patients in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) Trial. Circ Heart Fail 2013; 6(2): 184-92.
[4]
Steinberg BA, Zhao X, Heidenreich PA, et al. Trends in patients hospitalized with heart failure and preserved left ventricular ejection fraction: prevalence, therapies, and outcomes. Circulation 2012; 126: 65-75.
[5]
Bhatia RS, Tu JV, Lee DS, et al. Outcome of heart failure with preserved ejection fraction in a population-based study. N Engl J Med 2006; 355: 260-9.
[6]
Yancy CW, Lopatin M, Stevenson LW, et al. Clinical presentation, management, and in-hospital outcomes of patients admitted with acute decompensated heart failure with preserved systolic function: a report from the Acute Decompensated Heart Failure National Registry (ADHERE) Database. J Am Coll Cardiol 2006; 47: 76-84.
[7]
Lam CS, Carson PE, Anand IS, et al. Sex differences in clinical characteristics and outcomes in elderly patients with heart failure and preserved ejection fraction: the Irbesartan in Heart Failure with Preserved Ejection Fraction (I-PRESERVE) trial. Circ Heart Fail 2012; 5: 571-8.
[8]
Hoekstra T, Lesman-Leegte I, van Veldhuisen DJ, Sanderman R, Jaarsma T. Quality of life is impaired similarly in heart failure patients with preserved and reduced ejection fraction. Eur J Heart Fail 2011; 13: 1013-8.
[9]
Yang HX, Hou X, Lin P, Rong TH, Yang H, Fu JH. Survival and risk factors of surgically treated mediastinal invasion T4 non-small cell lung cancer. Ann Thorac Surg 2009; 88: 372-8.
[10]
Meta-analysis Global Group in Chronic Heart F. The survival of patients with heart failure with preserved or reduced left ventricular ejection fraction: an individual patient data meta-analysis. Eur Heart J 2012; 33: 1750-7.
[11]
Borlaug BA, Paulus WJ. Heart failure with preserved ejection fraction: pathophysiology, diagnosis, and treatment. Eur Heart J 2011; 32: 670-9.
[12]
Nagueh SF, Appleton CP, Gillebert TC, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. J Am Soc Echocardiogr 2009; 22: 107-33.
[14]
European Study Group on Diastolic Heart Failure How to diagnose diastolic heart failure. Eur Heart J 1998; 19: 990-1003.
[15]
Guidelines for the evaluation and management of heart failure. Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Evaluation and Management of Heart Failure). Circulation 1995; 92: 2764-84.
[16]
Maurer MS, Hummel SL. Heart failure with a preserved ejection fraction: what is in a name? J Am Coll Cardiol 2011; 58: 275-7.
[17]
Yu CM, Lin H, Yang H, Kong SL, Zhang Q, Lee SW. Progression of systolic abnormalities in patients with “isolated” diastolic heart failure and diastolic dysfunction. Circulation 2002; 105: 1195-201.
[18]
Borlaug BA, Lam CS, Roger VL, Rodeheffer RJ, Redfield MM. Contractility and ventricular systolic stiffening in hypertensive heart disease insights into the pathogenesis of heart failure with preserved ejection fraction. J Am Coll Cardiol 2009; 54: 410-8.
[19]
Borlaug BA, Melenovsky V, Russell SD, et al. Impaired chronotropic and vasodilator reserves limit exercise capacity in patients with heart failure and a preserved ejection fraction. Circulation 2006; 114: 2138-47.
[20]
Ennezat PV, Lefetz Y, Marechaux S, et al. Left ventricular abnormal response during dynamic exercise in patients with heart failure and preserved left ventricular ejection fraction at rest. J Card Fail 2008; 14: 475-80.
[21]
Kawaguchi M, Hay I, Fetics B, Kass DA. Combined ventricular systolic and arterial stiffening in patients with heart failure and preserved ejection fraction: implications for systolic and diastolic reserve limitations. Circulation 2003; 107: 714-20.
[22]
Brubaker PH, Joo KC, Stewart KP, Fray B, Moore B, Kitzman DW. Chronotropic incompetence and its contribution to exercise intolerance in older heart failure patients. J Cardiopulm Rehabil 2006; 26: 86-9.
[23]
Lam CSP, Roger VL, Rodeheffer RJ, Borlaug BA, Enders FT, Redfield MM. Pulmonary hypertension in heart failure with preserved ejection fraction. J Am Coll Cardiol 2009; 53: 1119-26.
[24]
Melenovsky V, Borlaug BA, Rosen B, et al. Cardiovascular features of heart failure with preserved ejection fraction versus nonfailing hypertensive left ventricular hypertrophy in the urban Baltimore community: the role of atrial remodeling/dysfunction. J Am Coll Cardiol 2007; 49: 198-207.
[25]
Maurer MS, Burkhoff D, Fried LP, Gottdiener J, King DL, Kitzman DW. Ventricular structure and function in hypertensive participants with heart failure and a normal ejection fraction: the Cardiovascular Health Study. J Am Coll Cardiol 2007; 49: 972-81.
[26]
Paulus WJ, van Ballegoij JJ. Treatment of heart failure with normal ejection fraction: an inconvenient truth. J Am Coll Cardiol 2010; 55: 526-37.
[27]
Prasad A, Hastings JL, Shibata S, et al. Characterization of static and dynamic left ventricular diastolic function in patients with heart failure with a preserved ejection fraction. Circ Heart Fail 2010; 3: 617-26.
[28]
Anjan VY, Loftus TM, Burke MA, et al. Prevalence, clinical phenotype, and outcomes associated with normal B-type natriuretic Peptide levels in heart failure with preserved ejection fraction. Am J Cardiol 2012; 110: 870-6.
[29]
Paulus WJ, Tschope C, Sanderson JE, et al. How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur Heart J 2007; 28: 2539-50.
[30]
Vasan RS, Levy D. Defining diastolic heart failure: a call for standardized diagnostic criteria. Circulation 2000; 101: 2118-21.
[31]
Yturralde RF, Gaasch WH. Diagnostic criteria for diastolic heart failure. Prog Cardiovasc Dis 2005; 47: 314-9.
[32]
Zile MR, Brutsaert DL. New concepts in diastolic dysfunction and diastolic heart failure: Part I: diagnosis, prognosis, and measurements of diastolic function. Circulation 2002; 105: 1387-93.
[33]
Meyer T, Shih J, Aurigemma G. Heart failure with preserved
ejection fraction (diastolic dysfunction). Ann Intern Med 2013; 158ITC5. : 1-15.
[34]
Heart Failure Society of A HFSA 2010 Comprehensive heart failure practice guideline. J Card Fail 2010; 16: e1-e194.
[35]
Jessup M, Abraham WT, Casey DE, et al. 2009 focused update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation 2009; 119: 1977-2016.
[36]
Maisel AS, Krishnaswamy P, Nowak RM, et al. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med 2002; 347: 161-7.
[37]
Maisel AS, McCord J, Nowak RM, et al. Bedside B-Type natriuretic peptide in the emergency diagnosis of heart failure with reduced or preserved ejection fraction. Results from the Breathing Not Properly Multinational Study. J Am Coll Cardiol 2003; 41: 2010-7.
[38]
Borlaug BA, Nishimura RA, Sorajja P, Lam CS, Redfield MM. Exercise hemodynamics enhance diagnosis of early heart failure with preserved ejection fraction. Circ Heart Fail 2010; 3: 588-95.
[39]
Iwanaga Y, Nishi I, Furuichi S, et al. B-type natriuretic peptide strongly reflects diastolic wall stress in patients with chronic heart failure: comparison between systolic and diastolic heart failure. J Am Coll Cardiol 2006; 47: 742-8.
[40]
Bursi F, Weston SA, Redfield MM, et al. Systolic and diastolic heart failure in the community. JAMA 2006; 296: 2209-16.
[41]
Kitzman DW, Little WC, Brubaker PH, et al. Pathophysiological characterization of isolated diastolic heart failure in comparison to systolic heart failure. JAMA 2002; 288: 2144-50.
[42]
Horwich TB, Hamilton MA, Fonarow GC. B-type natriuretic peptide levels in obese patients with advanced heart failure. J Am Coll Cardiol 2006; 47: 85-90.
[43]
Mehra MR, Uber PA, Park MH, et al. Obesity and suppressed B-type natriuretic peptide levels in heart failure. J Am Coll Cardiol 2004; 43: 1590-5.
[44]
Strange G, Playford D, Stewart S, et al. Pulmonary hypertension: prevalence and mortality in the Armadale echocardiography cohort. Heart 2012; 98: 1805-11.
[45]
McLaughlin VV, Archer SL, Badesch DB, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: developed in collaboration with the American College of Chest Physicians, American Thoracic Society, Inc., and the Pulmonary Hypertension Association. Circulation 2009; 119: 2250-94.
[47]
Ohara T, Ohte N, Little WC. Pulmonary hypertension in heart failure with preserved left ventricular ejection fraction: diagnosis and management. Curr Opin Cardiol 2012; 27: 281-7.
[48]
Thenappan T, Shah SJ, Gomberg-Maitland M, et al. Clinical characteristics of pulmonary hypertension in patients with heart failure and preserved ejection fraction. Circ Heart Fail 2011; 4: 257-65.
[49]
Willens HJ, Chirinos JA, Gomez-Marin O, et al. Noninvasive differentiation of pulmonary arterial and venous hypertension using conventional and Doppler tissue imaging echocardiography. J Am Soc Echocardiogr 2008; 21: 715-9.
[50]
Borlaug BA, Olson TP, Lam CS, et al. Global cardiovascular reserve dysfunction in heart failure with preserved ejection fraction. J Am Coll Cardiol 2010; 56: 845-54.
[51]
Kitzman DW, Higginbotham MB, Cobb FR, Sheikh KH, Sullivan MJ. Exercise intolerance in patients with heart failure and preserved left ventricular systolic function: failure of the Frank-Starling mechanism. J Am Coll Cardiol 1991; 17: 1065-72.
[52]
Burgess MI, Jenkins C, Sharman JE, Marwick TH. Diastolic stress echocardiography: hemodynamic validation and clinical significance of estimation of ventricular filling pressure with exercise. J Am Coll Cardiol 2006; 47: 1891-900.
[53]
Judge KW, Pawitan Y, Caldwell J, Gersh BJ, Kennedy JW. Congestive heart failure symptoms in patients with preserved left ventricular systolic function: analysis of the CASS registry. J Am Coll Cardiol 1991; 18: 377-82.
[54]
Choudhury L, Gheorghiade M, Bonow RO. Coronary artery disease in patients with heart failure and preserved systolic function. Am J Cardiol 2002; 89: 719-22.
[55]
Shah SJ. Evolving approaches to the management of heart failure with preserved ejection fraction in patients with coronary artery disease. Curr Treat Options Cardiovasc Med 2010; 12: 58-75.
[56]
Tschope C, Westermann D. Heart failure with normal ejection fraction. Pathophysiology, diagnosis, and treatment. Herz 2009; 34: 89-96.
[57]
Ahmed A, Rich MW, Fleg JL, et al. Effects of digoxin on morbidity and mortality in diastolic heart failure: the ancillary digitalis investigation group trial. Circulation 2006; 114: 397-403.
[58]
Flather MD, Shibata MC, Coats AJ, et al. Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J 2005; 26: 215-25.
[59]
van Veldhuisen DJ, Cohen-Solal A, Bohm M, et al. Beta-blockade with nebivolol in elderly heart failure patients with impaired and preserved left ventricular ejection fraction: Data from SENIORS (study of effects of nebivolol intervention on outcomes and rehospitalization in seniors with heart failure). J Am Coll Cardiol 2009; 53: 2150-8.
[60]
Cleland JG, Tendera M, Adamus J, et al. The perindopril in elderly people with chronic heart failure (PEP-CHF) study. Eur Heart J 2006; 27: 2338-45.
[61]
Yusuf S, Pfeffer MA, Swedberg K, et al. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. Lancet 2003; 362: 777-81.
[62]
Massie BM, Carson PE, McMurray JJ, et al. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med 2008; 359: 2456-67.
[63]
Edelmann F, Wachter R, Schmidt AG, et al. Effect of spironolactone on diastolic function and exercise capacity in patients with heart failure with preserved ejection fraction: the Aldo-DHF randomized controlled trial. JAMA 2013; 309: 781-91.
[64]
Liu Y, Haddad T, Dwivedi G. Heart failure with preserved ejection fraction: current understanding and emerging concepts. Curr Opin Cardiol 2013; 28: 187-96.
[65]
Guazzi M, Vicenzi M, Arena R, Guazzi MD. Pulmonary hypertension in heart failure with preserved ejection fraction: a target of phosphodiesterase-5 inhibition in a 1-year study. Circulation 2011; 124: 164-74.
[66]
Redfield MM, Chen HH, Borlaug BA, et al. Effect of Phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial. JAMA 2013; 309(12): 1268-77.
[67]
Solomon SD, Zile M, Pieske B, et al. The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomised controlled trial. Lancet 2012; 380: 1387-95.
[68]
Omori Y, Ohtani T, Sakata Y, et al. L-Carnitine prevents the development of ventricular fibrosis and heart failure with preserved ejection fraction in hypertensive heart disease. J Hypertens 2012; 30: 1834-44.
[69]
Reil JC, Hohl M, Reil GH, et al. Heart rate reduction by If-inhibition improves vascular stiffness and left ventricular systolic and diastolic function in a mouse model of heart failure with preserved ejection fraction. Eur Heart J 2013; 34(36): 2839-49.
[70]
Ather S, Chan W, Bozkurt B, et al. Impact of noncardiac comorbidities on morbidity and mortality in a predominantly male population with heart failure and preserved versus reduced ejection fraction. J Am Coll Cardiol 2012; 59: 998-1005.
[71]
Shah SJ, Gheorghiade M. Heart failure with preserved ejection fraction: treat now by treating comorbidities. JAMA 2008; 300: 431-3.
[72]
Kapoor JR, Heidenreich PA. Heart rate predicts mortality in patients with heart failure and preserved systolic function. J Card Fail 2010; 16: 806-11.
[73]
Maeder MT, Kaye DM. Differential impact of heart rate and blood pressure on outcome in patients with heart failure with reduced versus preserved left ventricular ejection fraction. Int J Cardiol 2012; 155: 249-56.
[74]
Massie BM, Nelson JJ, Lukas MA, et al. Comparison of outcomes and usefulness of carvedilol across a spectrum of left ventricular ejection fractions in patients with heart failure in clinical practice. Am J Cardiol 2007; 99: 1263-8.
[75]
Hernandez AF, Hammill BG, O’Connor CM, Schulman KA, Curtis LH, Fonarow GC. Clinical effectiveness of beta-blockers in heart failure: findings from the OPTIMIZE-HF (Organized program to initiate lifesaving treatment in hospitalized patients with heart failure) registry. J Am Coll Cardiol 2009; 53: 184-92.
[76]
Yamamoto K, Origasa H, Hori M, Investigators JD. Effects of carvedilol on heart failure with preserved ejection fraction: the Japanese Diastolic Heart Failure Study (J-DHF). Eur J Heart Fail 2013; 15: 110-8.
[77]
Oh JK, Hatle L, Tajik AJ, Little WC. Diastolic heart failure can be diagnosed by comprehensive two-dimensional and Doppler echocardiography. J Am Coll Cardiol 2006; 47: 500-6.
Article Metrics
143
5
1
1