Heart failure with preserved ejection fraction: Uncertainties and dilemmas

European Journal of Heart Failure

Volumn 17, Issue 7, 2015, Pages 665-671

  Ferrari, Roberto ^a   Böhm, Michael ^b   Cleland, John G F ^c   Paulus, Walter J S ^d   Pieske, Burkert ^e   Rapezzi, Claudio ^f   Tavazzi, Luigi ^g  

^a Ospedale di Cona   (Italy)

^b SAARLAND UNIVERSITY   (Germany)

^c HAREFIELD HOSPITAL   (United Kingdom)

^d VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^e MEDICAL UNIVERSITY OF GRAZ   (Austria)

^f UNIVERSITY OF BOLOGNA   (Italy)

^g MARIA CECILIA HOSPITAL   (Italy)

Author keywords

Heart failure; Preserved ejection fraction

Indexed keywords

ANGIOTENSIN RECEPTOR ANTAGONIST; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; ENDOTHELIN RECEPTOR ANTAGONIST; GUANYLATE CYCLASE ACTIVATOR; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; NATRIURETIC FACTOR; NEBIVOLOL; PLACEBO; SACUBITRIL PLUS VALSARTAN; SILDENAFIL; SPIRONOLACTONE; UNCLASSIFIED DRUG; VALSARTAN; VERCIGUAT; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; DIURETIC AGENT;

AGE DISTRIBUTION; ARTICLE; ATRIAL FIBRILLATION; CLINICAL FEATURE; CLINICAL TRIAL (TOPIC); COMORBIDITY; DIASTOLIC DYSFUNCTION; HEART ATRIUM ENLARGEMENT; HEART FAILURE WITH PRESERVED EJECTION FRACTION; HEART LEFT VENTRICLE FILLING; HEART LEFT VENTRICLE HYPERTROPHY; HEART LEFT VENTRICLE RELAXATION; HOSPITAL ADMISSION; HUMAN; HYPERTENSION; LIFESTYLE MODIFICATION; META ANALYSIS (TOPIC); METABOLIC SYNDROME X; MICROELECTROMECHANICAL PRESSURE SENSOR; MICROELECTROMECHANICAL SYSTEM; PATHOPHYSIOLOGY; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROGNOSIS; PROTEIN BLOOD LEVEL; RANDOMIZED CONTROLLED TRIAL (TOPIC); RISK FACTOR; SENSOR; SYMPTOM; HEART FAILURE; HEART STROKE VOLUME; PHYSIOLOGY;

ADRENERGIC BETA-ANTAGONISTS; ANGIOTENSIN RECEPTOR ANTAGONISTS; DIURETICS; HEART FAILURE; HUMANS; PROGNOSIS; SPIRONOLACTONE; STROKE VOLUME;

EID: 84947866951     PISSN: 13889842     EISSN: 18790844     Source Type: Journal    
DOI: 10.1002/ejhf.304     Document Type: Article

References (77)

1. Gandhi SK, Powers JC, Nomeir AM, Fowle K, Kitzman DW, Rankin KM, Little WC,. The pathogenesis of acute pulmonary edema associated with hypertension. N Engl J Med 2001; 344: 17-22.
2. Sanderson JE,. HFNEF, HFpEF, HF-PEF, or DHF: what is in an acronym? JACC Heart Fail 2014; 2: 93-94.
3. McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, Kober L, Lip GY, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, Ronnevik PK, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A, Bax JJ, Baumgartner H, Ceconi C, Dean V, Deaton C, Fagard R, Funck-Brentano C, Hasdai D, Hoes A, Kirchhof P, Knuuti J, Kolh P, McDonagh T, Moulin C, Reiner Z, Sechtem U, Sirnes PA, Tendera M, Torbicki A, Vahanian A, Windecker S, Bonet LA, Avraamides P, Ben Lamin HA, Brignole M, Coca A, Cowburn P, Dargie H, Elliott P, Flachskampf FA, Guida GF, Hardman S, Iung B, Merkely B, Mueller C, Nanas JN, Nielsen OW, Orn S, Parissis JT, Ponikowski P,. 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; 14: 803-869.
4. Iwanaga Y, Nishi I, Furuichi S, Noguchi T, Sase K, Kihara Y, Goto Y, Nonogi H,. 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: 742-748.
5. McKelvie RS, Komajda M, McMurray J, Zile M, Ptaszynska A, Donovan M, Carson P, Massie BM,. Baseline plasma NT-proBNP and clinical characteristics: results from the irbesartan in heart failure with preserved ejection fraction trial. J Card Fail 2010; 16: 128-134.
6. Anjan VY, Loftus TM, Burke MA, Akhter N, Fonarow GC, Gheorghiade M, Shah SJ,. 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: 870-876.
7. Hancock HC, Close H, Mason JM, Murphy JJ, Fuat A, Singh R, Wood E, de Belder M, Brennan G, Hussain N, Kumar N, Wilson D, Hungin AP,. High prevalence of undetected heart failure in long-term care residents: findings from the Heart Failure in Care Homes (HFinCH) study. Eur J Heart Fail 2013; 15: 158-165.
8. Paulus WJ, Tschope C, Sanderson JE, Rusconi C, Flachskampf FA, Rademakers FE, Marino P, Smiseth OA, De Keulenaer G, Leite-Moreira AF, Borbely A, Edes I, Handoko ML, Heymans S, Pezzali N, Pieske B, Dickstein K, Fraser AG, Brutsaert DL,. 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: 2539-2550.
9. Melenovsky V, Hwang SJ, Lin G, Redfield MM, Borlaug BA,. Right heart dysfunction in heart failure with preserved ejection fraction. Eur Heart J 2014; 35: 3452-3462.
10. Mohammed SF, Hussain I, Abou Ezzeddine OF, Takahama H, Kwon SH, Forfia P, Roger VL, Redfield MM,. Right ventricular function in heart failure with preserved ejection fraction: a community-based study. Circulation 2014; 130: 2310-2320.
11. Zile MR, Gottdiener JS, Hetzel SJ, McMurray JJ, Komajda M, McKelvie R, Baicu CF, Massie BM, Carson PE,. Prevalence and significance of alterations in cardiac structure and function in patients with heart failure and a preserved ejection fraction. Circulation 2011; 124: 2491-2501.
12. Campbell RT, Jhund PS, Castagno D, Hawkins NM, Petrie MC, McMurray JJ,. What have we learned about patients with heart failure and preserved ejection fraction from DIG-PEF, CHARM-preserved, and I-PRESERVE? J Am Coll Cardiol 2012; 60: 2349-2356.
13. Bhatia RS, Tu JV, Lee DS, Austin PC, Fang J, Haouzi A, Gong Y, Liu PP,. Outcome of heart failure with preserved ejection fraction in a population-based study. N Engl J Med 2006; 355: 260-269.
14. Meta-analysis Global Group in Chronic Heart Failure. 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: 1750-1757.
15. Burkhoff D., Mortality in heart failure with preserved ejection fraction: an unacceptably high rate. Eur Heart J 2012; 33: 1718-1720.
16. Brouwers FP, de Boer RA, van der Harst P, Voors AA, Gansevoort RT, Bakker SJ, Hillege HL, Van Veldhuisen DJ, Van Gilst WH,. Incidence and epidemiology of new onset heart failure with preserved vs. reduced ejection fraction in a community-based cohort: 11-year follow-up of PREVEND. Eur Heart J 2013; 34: 1424-1431.
17. Fonarow GC, Stough WG, Abraham WT, Albert NM, Gheorghiade M, Greenberg BH, O'Connor CM, Sun JL, Yancy CW, Young JB,. Characteristics, treatments, and outcomes of patients with preserved systolic function hospitalized for heart failure: a report from the OPTIMIZE-HF Registry. J Am Coll Cardiol 2007; 50: 768-777.
18. Bello NA, Claggett B, Desai AS, McMurray JJ, Granger CB, Yusuf S, Swedberg K, Pfeffer MA, Solomon SD,. Influence of previous heart failure hospitalization on cardiovascular events in patients with reduced and preserved ejection fraction. Circ Heart Fail 2014; 7: 590-595.
19. Carlsen CM, Bay M, Kirk V, Gotze JP, Kober L, Nielsen OW,. Prevalence and prognosis of heart failure with preserved ejection fraction and elevated N-terminal pro brain natriuretic peptide: a 10-year analysis from the Copenhagen Hospital Heart Failure Study. Eur J Heart Fail 2012; 14: 240-247.
20. Zile MR, Gaasch WH, Anand IS, Haass M, Little WC, Miller AB, Lopez-Sendon J, Teerlink JR, White M, McMurray JJ, Komajda M, McKelvie R, Ptaszynska A, Hetzel SJ, Massie BM, Carson PE,. Mode of death in patients with heart failure and a preserved ejection fraction: results from the Irbesartan in Heart Failure With Preserved Ejection Fraction Study (I-Preserve) trial. Circulation 2010; 121: 1393-1405.
21. Senni M, Gavazzi A, Oliva F, Mortara A, Urso R, Pozzoli M, Metra M, Lucci D, Gonzini L, Cirrincione V, Montagna L, Di Lenarda A, Maggioni AP, Tavazzi L,; IN HF Outcome Investigators. In-hospital and 1-year outcomes of acute heart failure patients according to presentation (de novo vs. worsening) and ejection fraction. Results from IN-HF Outcome Registry. Int J Cardiol 2014; 173: 163-169.
22. Komajda M, Lam CS,. Heart failure with preserved ejection fraction: a clinical dilemma. Eur Heart J 2014; 35: 1022-1032.
23. Chan MM, Lam CS,. How do patients with heart failure with preserved ejection fraction die? Eur J Heart Fail 2013; 15: 604-613.
24. Borlaug BA,. The pathophysiology of heart failure with preserved ejection fraction. Nat Rev Cardiol 2014; 11: 507-515
25. Butler J, Fonarow GC, Zile MR, Lam CS, Roessig L, Schelbert EB, Shah SJ, Ahmed A, Bonow RO, Cleland JG, Cody RJ, Chioncel O, Collins SP, Dunnmon P, Filippatos G, Lefkowitz MP, Marti CN, McMurray JJ, Misselwitz F, Nodari S, O'Connor C, Pfeffer MA, Pieske B, Pitt B, Rosano G, Sabbah HN, Senni M, Solomon SD, Stockbridge N, Teerlink JR, Georgiopoulou VV, Gheorghiade M,. Developing therapies for heart failure with preserved ejection fraction: current state and future directions. JACC Heart Fail 2014; 2: 97-112.
26. Cleland JG, Pellicori P, Dierckx R,. Clinical trials in patients with heart failure and preserved left ventricular ejection fraction. Heart Fail Clin 2014; 10: 511-523.
27. De Keulenaer GW, Brutsaert DL,. Systolic and diastolic heart failure: different phenotypes of the same disease? Eur J Heart Fail 2007; 9: 136-143.
28. Senni M, Paulus WJ, Gavazzi A, Fraser AG, Diez J, Solomon SD, Smiseth OA, Guazzi M, Lam CS, Maggioni AP, Tschope C, Metra M, Hummel SL, Edelmann F, Ambrosio G, Stewart Coats AJ, Filippatos GS, Gheorghiade M, Anker SD, Levy D, Pfeffer MA, Stough WG, Pieske BM,. New strategies for heart failure with preserved ejection fraction: the importance of targeted therapies for heart failure phenotypes. Eur Heart J 2014; 35: 2797-2815.
29. Clarke CL, Grunwald GK, Allen LA, Baron AE, Peterson PN, Brand DW, Magid DJ, Masoudi FA,. Natural history of left ventricular ejection fraction in patients with heart failure. Circ Cardiovasc Qual Outcomes 2013; 6: 680-686.
30. 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: 251-259.
31. Paulus WJ, Tschope C,. A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J Am Coll Cardiol 2013; 62: 263-271.
32. Ammar KA, Redfield MM, Mahoney DW, Johnson M, Jacobsen SJ, Rodeheffer RJ,. Central obesity: association with left ventricular dysfunction and mortality in the community. Am Heart J 2008; 156: 975-981.
33. Redfield MM, Jacobsen SJ, Burnett JC Jr, Mahoney DW, Bailey KR, Rodeheffer RJ,. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA 2003; 289: 194-202.
34. Borbely A, Van der Velden J, Papp Z, Bronzwaer JG, Edes I, Stienen GJ, Paulus WJ,. Cardiomyocyte stiffness in diastolic heart failure. Circulation 2005; 111: 774-781.
35. van Heerebeek L., Borbely A, Niessen HW, Bronzwaer JG, Van der Velden J, Stienen GJ, Linke WA, Laarman GJ, Paulus WJ., Myocardial structure and function differ in systolic and diastolic heart failure. Circulation 2006; 113: 1966-1973.
36. van Heerebeek L., Hamdani N, Handoko ML, Falcao-Pires I, Musters RJ, Kupreishvili K, Ijsselmuiden AJ, Schalkwijk CG, Bronzwaer JG, Diamant M, Borbely A, Van der Velden J, Stienen GJ, Laarman GJ, Niessen HW, Paulus WJ., Diastolic stiffness of the failing diabetic heart: importance of fibrosis, advanced glycation end products, and myocyte resting tension. Circulation 2008; 117: 43-51.
37. Zile MR, Baicu CF, Ikonomidis J, Stroud RE, Nietert PJ, Bradshaw AD, Slater R, Palmer BM, Van Buren P, Meyer M, Redfield M, Bull D, Granzier H, LeWinter MM,. Myocardial stiffness in patients with heart failure and a preserved ejection fraction: contributions of collagen and titin. Circulation 2015; 131: 1247-1259.
38. Westermann D, Lindner D, Kasner M, Zietsch C, Savvatis K, Escher F, von SJ, Skurk C, Steendijk P, Riad A, Poller W, Schultheiss HP, Tschope C,. Cardiac inflammation contributes to changes in the extracellular matrix in patients with heart failure and normal ejection fraction. Circ Heart Fail 2011; 4: 44-52.
39. van Heerebeek L., Hamdani N, Falcao-Pires I, Leite-Moreira AF, Begieneman MP, Bronzwaer JG, Van der Velden J, Stienen GJ, Laarman GJ, Somsen A, Verheugt FW, Niessen HW, Paulus WJ., Low myocardial protein kinase G activity in heart failure with preserved ejection fraction. Circulation 2012; 126: 830-839.
40. Borlaug BA, Redfield MM, Melenovsky V, Kane GC, Karon BL, Jacobsen SJ, Rodeheffer RJ,. Longitudinal changes in left ventricular stiffness: a community-based study. Circ Heart Fail 2013; 6: 944-952.
41. Nagayama T, Hsu S, Zhang M, Koitabashi N, Bedja D, Gabrielson KL, Takimoto E, Kass DA,. Sildenafil stops progressive chamber, cellular, and molecular remodeling and improves calcium handling and function in hearts with pre-existing advanced hypertrophy caused by pressure overload. J Am Coll Cardiol 2009; 53: 207-215.
42. Redfield MM, Chen HH, Borlaug BA, Semigran MJ, Lee KL, Lewis G, LeWinter MM, Rouleau JL, Bull DA, Mann DL, Deswal A, Stevenson LW, Givertz MM, Ofili EO, O'Connor CM, Felker GM, Goldsmith SR, Bart BA, McNulty SE, Ibarra JC, Lin G, Oh JK, Patel MR, Kim RJ, Tracy RP, Velazquez EJ, Anstrom KJ, Hernandez AF, Mascette AM, Braunwald E,. 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: 1268-1277.
43. Cleland JG, Tendera M, Adamus J, Freemantle N, Polonski L, Taylor J,. The perindopril in elderly people with chronic heart failure (PEP-CHF) study. Eur Heart J 2006; 27: 2338-2345.
44. Yusuf S, Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, Olofsson B, Ostergren J,. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. Lancet 2003; 362: 777-781.
45. Massie BM, Carson PE, McMurray JJ, Komajda M, McKelvie R, Zile MR, Anderson S, Donovan M, Iverson E, Staiger C, Ptaszynska A,. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med 2008; 359: 2456-2467.
46. Edwards NC, Steeds RP, Stewart PM, Ferro CJ, Townend JN,. Effect of spironolactone on left ventricular mass and aortic stiffness in early-stage chronic kidney disease: a randomized controlled trial. J Am Coll Cardiol 2009; 54: 505-512.
47. Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B, Clausell N, Desai AS, Diaz R, Fleg JL, Gordeev I, Harty B, Heitner JF, Kenwood CT, Lewis EF, O'Meara E, Probstfield JL, Shaburishvili T, Shah SJ, Solomon SD, Sweitzer NK, Yang S, McKinlay SM,. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med 2014; 370: 1383-1392.
48. McMurray JJ, O'Connor C,. Lessons from the TOPCAT trial. N Engl J Med 2014; 370: 1453-1454.
49. Pfeffer MA, Claggett B, Assmann SF, Boineau R, Anand IS, Clausell N, Desai AS, Diaz R, Fleg JL, Gordeev I, Heitner JF, Lewis EF, O'Meara E, Rouleau JL, Probstfield JL, Shaburishvili T, Shah SJ, Solomon SD, Sweitzer NK, McKinlay SM, Pitt B,. regional variation in patients and outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) Trial. Circulation 2015; 131: 34-42.
50. Capomolla S, Febo O, Gnemmi M, Riccardi G, Opasich C, Caporotondi A, Mortara A, Pinna GD, Cobelli F,. Beta-blockade therapy in chronic heart failure: diastolic function and mitral regurgitation improvement by carvedilol. Am Heart J 2000; 139: 596-608.
51. Van Veldhuisen DJ, Cohen-Solal A, Bohm M, Anker SD, Babalis D, Roughton M, Coats AJ, Poole-Wilson PA, Flather MD,. 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: 2150-2158.
52. Van Veldhuisen DJ, McMurray JJ,. Pharmacological treatment of heart failure with preserved ejection fraction: a glimpse of light at the end of the tunnel? Eur J Heart Fail 2013; 15: 5-8.
53. Bavishi C, Chatterjee S, Ather S, Patel D, Messerli FH,. Beta-blockers in heart failure with preserved ejection fraction: a meta-analysis. Heart Fail Rev 2015; 20: 193-201.
54. Hartog JW, Voors AA, Bakker SJ, Smit AJ, Van Veldhuisen DJ,. Advanced glycation end-products (AGEs) and heart failure: pathophysiology and clinical implications. Eur J Heart Fail 2007; 9: 1146-1155.
55. Little WC, Zile MR, Kitzman DW, Hundley WG, O'Brien TX, Degroof RC,. The effect of alagebrium chloride (ALT-711), a novel glucose cross-link breaker, in the treatment of elderly patients with diastolic heart failure. J Card Fail 2005; 11: 191-195.
56. Hartog JW, Willemsen S, Van Veldhuisen DJ, Posma JL, van Wijk LM, Hummel YM, Hillege HL, Voors AA,. Effects of alagebrium, an advanced glycation endproduct breaker, on exercise tolerance and cardiac function in patients with chronic heart failure. Eur J Heart Fail 2011; 13: 899-908.
57. Kjekshus J, Pedersen TR, Olsson AG, Faergeman O, Pyorala K,. The effects of simvastatin on the incidence of heart failure in patients with coronary heart disease. J Card Fail 1997; 3: 249-254.
58. Takemoto M, Node K, Nakagami H, Liao Y, Grimm M, Takemoto Y, Kitakaze M, Liao JK,. Statins as antioxidant therapy for preventing cardiac myocyte hypertrophy. J Clin Invest 2001; 108: 1429-1437.
59. Patel R, Nagueh SF, Tsybouleva N, Abdellatif M, Lutucuta S, Kopelen HA, Quinones MA, Zoghbi WA, Entman ML, Roberts R, Marian AJ,. Simvastatin induces regression of cardiac hypertrophy and fibrosis and improves cardiac function in a transgenic rabbit model of human hypertrophic cardiomyopathy. Circulation 2001; 104: 317-324.
60. Fukuta H, Sane DC, Brucks S, Little WC,. Statin therapy may be associated with lower mortality in patients with diastolic heart failure: a preliminary report. Circulation 2005; 112: 357-363.
61. Lenzen MJ, Scholte op Reimer WJ, Boersma E, Vantrimpont PJ, Follath F, Swedberg K, Cleland J, Komajda M,. Differences between patients with a preserved and a depressed left ventricular function: a report from the EuroHeart Failure Survey. Eur Heart J 2004; 25: 1214-1220.
62. Liu G, Zheng XX, Xu YL, Ru J, Hui RT, Huang XH,. Meta-analysis of the effect of statins on mortality in patients with preserved ejection fraction. Am J Cardiol 2014; 113: 1198-1204.
63. Tavazzi L, Maggioni AP, Marchioli R, Barlera S, Franzosi MG, Latini R, Lucci D, Nicolosi GL, Porcu M, Tognoni G,. Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet 2008; 372: 1231-1239.
64. Kjekshus J, Apetrei E, Barrios V, Bohm M, Cleland JG, Cornel JH, Dunselman P, Fonseca C, Goudev A, Grande P, Gullestad L, Hjalmarson A, Hradec J, Janosi A, Kamensky G, Komajda M, Korewicki J, Kuusi T, Mach F, Mareev V, McMurray JJ, Ranjith N, Schaufelberger M, Vanhaecke J, Van Veldhuisen DJ, Waagstein F, Wedel H, Wikstrand J,. Rosuvastatin in older patients with systolic heart failure. N Engl J Med 2007; 357: 2248-2261.
65. Solomon SD, Zile M, Pieske B, Voors A, Shah A, Kraigher-Krainer E, Shi V, Bransford T, Takeuchi M, Gong J, Lefkowitz M, Packer M, McMurray JJ,. The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomised controlled trial. Lancet 2012; 380: 1387-1395.
66. Pieske B, Butler J, Filippatos G, Lam C, Maggioni AP, Ponikowski P, Shah S, Solomon S, Kraigher-Krainer E, Samano ET, Scalise AV, Muller K, Roessig L, Gheorghiade M,. Rationale and design of the SOluble guanylate Cyclase stimulatoR in heArT failurE Studies (SOCRATES). Eur J Heart Fail 2014; 16: 1026-1038.
67. Maltsev VA, Sabbah HN, Higgins RS, Silverman N, Lesch M, Undrovinas AI,. Novel, ultraslow inactivating sodium current in human ventricular cardiomyocytes. Circulation 1998; 98: 2545-2552.
68. Valdivia CR, Chu WW, Pu J, Foell JD, Haworth RA, Wolff MR, Kamp TJ, Makielski JC,. Increased late sodium current in myocytes from a canine heart failure model and from failing human heart. J Mol Cell Cardiol 2005; 38: 475-483.
69. Hayashida W, van Eyil C, Rousseau MF, Pouleur H,. Effects of ranolazine on left ventricular regional diastolic function in patients with ischemic heart disease. Cardiovasc Drugs Ther 1994; 8: 741-747.
70. Maier LS, Layug B, Karwatowska-Prokopczuk E, Belardinelli L, Lee S, Sander J, Lang C, Wachter R, Edelmann F, Hasenfuss G, Jacobshagen C,. RAnoLazIne for the treatment of diastolic heart failure in patients with preserved ejection fraction: the RALI-DHF proof-of-concept study. JACC Heart Fail 2013; 1: 115-122.
71. Kapoor JR, Heidenreich PA,. Heart rate predicts mortality in patients with heart failure and preserved systolic function. J Card Fail 2010; 16: 806-811.
72. Bohm M, Perez AC, Jhund PS, Reil JC, Komajda M, Zile MR, McKelvie RS, Anand IS, Massie BM, Carson PE, McMurray JJ,. Relationship between heart rate and mortality and morbidity in the irbesartan patients with heart failure and preserved systolic function trial (I-Preserve). Eur J Heart Fail 2014; 16: 778-787.
73. Colin P, Ghaleh B, Hittinger L, Monnet X, Slama M, Giudicelli JF, Berdeaux A,. Differential effects of heart rate reduction and beta-blockade on left ventricular relaxation during exercise. Am J Physiol Heart Circ Physiol 2002; 282: H672-H679.
74. Kosmala W, Holland DJ, Rojek A, Wright L, Przewlocka-Kosmala M, Marwick TH,. Effect of If-channel inhibition on hemodynamic status and exercise tolerance in heart failure with preserved ejection fraction: a randomized trial. J Am Coll Cardiol 2013; 62: 1330-1338.
75. Reil JC, Hohl M, Reil GH, Granzier HL, Kratz MT, Kazakov A, Fries P, Muller A, Lenski M, Custodis F, Graber S, Frohlig G, Steendijk P, Neuberger HR, Bohm M,. 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: 2839-2849.
76. Adamson PB, Abraham WT, Bourge RC, Costanzo MR, Hasan A, Yadav C, Henderson J, Cowart P, Stevenson LW,. Wireless pulmonary artery pressure monitoring guides management to reduce decompensation in heart failure with preserved ejection fraction. Circ Heart Fail 2014; 7: 935-944.
77. Haykowsky MJ, Brubaker PH, Stewart KP, Morgan TM, Eggebeen J, Kitzman DW,. Effect of endurance training on the determinants of peak exercise oxygen consumption in elderly patients with stable compensated heart failure and preserved ejection fraction. J Am Coll Cardiol 2012; 60: 120-128.