Review

March 2016, 24:4

First online: 08 March 2016

Review

Chronic Heart Failure Clinical Practice Guidelines’ Class 1-A Pharmacologic Recommendations: Start-to-End Synergistic Drug Therapy?

Ramon F. Abarquez Jr. MD,¹ Paul Ferdinand M. Reganit MD, MPH,¹ Carmen N. Chungunco MD,¹ Jean Alcover MD,¹ Felix Eduardo R. Punzalan MD,¹ Eugenio B. Reyes MD,¹ Elleen L. Cunanan MD¹

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Summary

Background:

Chronic heart failure (HF) disease as an emerging epidemic has a high economic-psycho-social burden, hospitalization, readmission, morbidity and mortality rates despite many clinical practice guidelines’ evidenced-based and consensus driven recommendations that include trials’ initial-baseline data.

Objective:

To show that the survival and hospitalization-free event rates in the reviewed chronic HF clinical practice guidelines’ class I-A recommendations as initial HF drug therapy (IDT) is possibly a combination and ‘start-to-end’ synergistic effect of the add-on (‘end’) HF drug therapy (ADT) to the baseline (‘start’) HF drug therapy (BDT).

Methodology:

The references cited in the chronic HF clinical practice guidelines of the 2005, 2009, and 2013 American Heart Association/American College of Cardiology (AHA/ACC), the 2006 Heart Failure Society of America (HFSA), and the 2005, 2008, and 2012 European Society of Cardiology (ESC) were reviewed and compared with the respective guidelines’ and other countries’ recommendations.

Results:
The BDT using glycosides and diuretics is 79%-100% in the cited HF trials. The survival rates attributed to the BDT (‘start’) is 46%-89% and IDT (‘end’) 61%-92.8%, respectively. The hospitalization-free event rate of the BDT group: 47.1% to 85.3% and IDT group 61.8%-90%, respectively. Thus, the survival and hospitalization-free event rates of the ADT is 0.4%-15% and 4.6% to 14.7%, respectively. The extrapolated BDT survival is 8%-51% based on a 38% estimated natural HF survival rate for the time period109.

Conclusion:
The contribution of baseline HF drug therapy (BDT) is relevant in terms of survival and hospitalization-free event rates compared to the HF class 1-A guidelines initial drug therapy recommendations (IDT). Further, the proposed initial HF drug (‘end’) therapy (IDT) has possible synergistic effects with the baseline HF drug (‘start’) therapy (BDT) and is essentially the add on HF drug therapy (ADT) in our analysis. The polypharmacy HF treatment is a synergistic effect due to BDT and ADT.

Keywords:
Heart failure - analysis - clinical practice guidelines

Section of Cardiology, Department of Medicine, University of the Philippines, College of Medicine and Philippine General Hospital, Manila

Address correspondence and reprint requests to: Paul M. Reganit, MD, MPH, Section of Cardiology, University of the Philippines - Philippine General Hospital, 6/F, PGH Compound, Taft Avenue, Manila, Philippines 1000. Telephone: 632.708.0000 or email at preganit@post.harvard.edu.

Open Access: This article is distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0) which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

Supplementary Material

Nil

References

1. Hedberg P, Lonnberg I, Jonasson T, et al. Left ventricular systolic dysfunction in 75-year old men and women: a population-based study. Eur Heart J 2001;22:676-683. CrossRef

2. Nielson OW, Hilden J, Larsen CT, et al. Cross sectional study estimating prevalence of heart failure and left ventricular systolic dysfunction in community patients at risk. Heart 2001;86:172-178. CrossRef

3. Cortina A, Reguero J, Segovia E, et al. Prevalence of heart failure in Asturias (a region in north of Spain). Am J Cardiol 2001;87:1417-1419. CrossRef

4. Ceia F, Fonseca C, Mota T, et al. Prevalence of chronic heart failure in Southwestern Europe: EPICA study. Eur J Heart Fail 2002;4:531-539. CrossRef

5. Redfield MM, Jacobsen SJ, Burnett JC Jr, et al. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA 2003;289:194-202. PubMed CrossRef

6. Shi C, Wang LJ, Hu DF, Li JP, Zhu TQ, Shan Y, Zhao JR, Zhang FR, Shen WF Prevalence, clinical characteristics and outcome in patients with chronic heart failure and diabetes. China Medical Journal 2010; 123:646-50.

7. Bueno H, Ross JS, Wang Y, Chen J, Vidán MT, Normand SLT, Curtis JP, Drye EE, Lichtman JH, Keenan PS, Kosiborod M, Krumholz HM. Trends in Length of Stay and Short-Term Outcomes among Medicare Patients Hospitalized for Heart Failure: 1993-2008. JAMA 2010;303(21):2141-2147. PubMed PubMedCentral CrossRef

8. Mulvey GK, Wang Y, Lin Z, Wang OJ, Chen J, Keenan PS, Drye EE, et al. Mortality and Readmission for Patients With Heart Failure Among U.S. News & World Report’s Top Heart Hospitals. Circ Cardiovasc Qual Outcomes. 2009;2:558-565. PubMed CrossRef

9. Senni, M.; Tribouilloy, C.M.; Rodeheffer, R.J.; Jacobsen, S.J.; Evans, J.M.; Bailey, K.R.; Redfield, M.M. Congestive heart failure in the community: trends in incidence and survival in a 10-year period. Arch. Intern. Med. 1999,159,29-34. PubMed CrossRef

10. Ho, K.K.; Anderson, K.M.; Kannel, W.B.; Grossman, W.; Levy, D. Survival after the onset of congestive heart failure in Framingham Heart Study subjects. Circulation 1993,88, 107-115. PubMed CrossRef

11. MacIntyre, K.; Capewell, S.; Stewart, S.; Chalmers, J.W.; Boyd, J.; Finlayson, A.; Redpath, A.; Pell, J.P.; McMurray, J.J. Evidence of improving prognosis in heart failure: trends in case fatality in 66 547 patients hospitalized between 1986 and 1995. Circulation 2000,102,1126-113. >PubMed CrossRef

12. Fonarow GC, Heywood T, Heidenreich PA, Lopatin M, Yancy CW for the ADHERE Scientific Advisory Committee and Investigators. Temporal trends in clinical characteristics, treatments, and outcomes for heart failure hospitalizations, 2002 to 2004: findings from Acute Decompensated Heart Failure National Registry (ADHERE) Am Heart J 2007;153:102128.

13. Baliga V, Sapsford R. Diabetes mellitus and heart failure - an overview of epidemiology and management. Diabetes & Vascular Disease Research 2009;6(3)164-171.

14. Fonarow GC, Albert NM, Curtis AB, Stough WG, et al. Improved Evidence-based Care for Heart Failure in Outpatient Cardiology Practices. Circulation 2010;122:585-596. PubMed CrossRef

15. Fonarow GC, Improving Quality of Care and Outcomes for Heart Failure: Role of Registries. Circ J 2011;75:1783-1790. PubMed CrossRef

16. Owens, AT, Jessup, M The Year in Heart Failure, JACC 2012;60 (5):359-368. PubMed CrossRef

17. Szucs TD The growing healthcare burden of CHF. J Renin Angiotensin-Aldosterone System 2000;1(S1):2-6. CrossRef

18. Foraker RE, Rose KM, Chang PP, Suchindran CM, McNeill AM, Rosamond WDHospital Length of Stay for Incident Heart Failure: Atherosclerosis Risk in Communities (ARIC) Cohort: 1987-2005 J Healthc Qual. 2012 Dec 3.doi: 10.1111/j.1945-147-4.

19. McAlister FA, Stewart S, Ferrua S, McMurray JJ. Multidisciplinary strategies for the management of heart failure patients at high risk for admission: a systematic review of randomized trials. J Am Coll Cardiol. 2004;44:810-819. PubMed

20. Ng TMH, Pharm D, Dasta JF, Durtschi AJ, McLaughlin TP, Feldman DS, Characteristics, Drug Therapy, and Outcomes From a Database of 500,000 Hospitalized Patients With a Discharge Diagnosis of Heart Failure. Congest Heart Fail. 2008;14:202-210. PubMed CrossRef

21.S mith DH, Johnson ES, Blough DK, Thorp ML, Yang X, Petrik AF, Crispell KA. Predicting costs of care in heart failure patients BMC Health Serv Res. 2012 Nov 30;12:434.

22. Tevendale E, Baxter J. Heart failure comorbidities at the end of life Curr Opin Support Palliat Care. 2011 Dec;5(4):322-6.

23.L eentjens AF, Burgers JS What factors are important for the successful implementation of guidelines. Tijdschr Psychiatr. 2008;50(6):329-35. PubMed

24. Kaul S, Diamond GA, Trial and Error. How to Avoid Commonly Encountered Limitations of Published Clinical Trials, J Am Coll Cardiol 2010;55:415–27 Stone GW, Pocock SJ, Randomized Trials, Statistics, and Clinical Inference. J Am Coll Cardiol 2010;55:428-31. CrossRef

25. Granger, CB and Gersh, BJ, Clinical trials and registries in cardiovascular disease: competitive or complementary? European Heart Journal 2010;31:520-21. PubMed CrossRef

26. McMurray JJV, Systolic Heart Failure, N Engl J Med 2010;362:228-38. PubMed CrossRef

27. McAlister FA, Stewart S, Ferrua S, McMurray JJV. Multidisciplinary Strategies for the Management of Heart Failure Patients at High Risk for Admission. A Systematic Review of Randomized Trials. J Am Coll Cardiol 2004;44:810-9. PubMed

28. Leykum LK, Parchman M, Pugh J, Lawrence V, Noël PH, n R McDaniel RR Jr. The importance of organizational characteristics for improving outcomes in patients with chronic disease: a systematic review of congestive heart failure. Science 2010,5:66-75.

29. Gonseth J, Guallar-Castillon J, Banegas JR, Rodrıguez-Artalejo F. The effectiveness of disease management programmes in reducing hospital re-admission in older patients with heart failure: a systematic review and metaanalysis of published reports. European Heart Journal (2004) 25,1570-159. PubMed CrossRef

30. Muth C, Gensichen J, Beyer M, Hutchinson A, Gerlach FM. The systematic guideline review: method, rationale and test on chronic heart failure. BMC Health Service Research 2009;9:74-89. CrossRef

31. Clark AM, Savard LA, Thompson DR What Is the Strength of Evidence for Heart Failure Disease-Management Programs? J Am Coll Cardiol 2009;54:397-401 Follalth F. Challenging the dogma of high target doses in the treatment of heart failure: is more always better? Archive Cardiovascular Disease 2009;102(11):785-9. CrossRef

32. Cleland JGF, Cullington D. Digoxin, Quo Vadis. Circ Heart Fail 2009;2:81-85. Becker H, Sigmund M. [Therapy of heart failure. Digitalis, diuretic plus ACE inhibitor or more?]. Internist (Berl). 1995 Dec;36(12):1117-23.

33. Manuel Anguita* (co-ordinator), Josep Comin (co-ordinator Comments on the ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012. A Report of the Task Force of the Clinical Practice Guidelines Committee of the Spanish Society of Cardiology Working Group of the Spanish Society of Cardiology on the ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012:), Rev Esp Cardiol. 2012;65(10):874-878.

34. Richter B, Koller L, Hohensinner PJ, Zorn G, Brekalo M, Berger R, Mörtl D, Maurer G, Pacher R, Huber K, Wojta J, Hülsmann M, Niessner AA multi-biomarker risk score improves prediction of long-term mortality in patients with advanced heart failure. Int J Cardiol. 2012 Dec 3. pii: S0167-5273(12)01535-5.

35. Accad M and Fred HL. Is Jupiter also a God of primary prevention? Texas Heart Institute Journal 2010;37:6-7. PubMed PubMedCentral

36. Becker H, Sigmund M. [Therapy of heart failure. Digitalis, diuretic plus ACE inhibitor or more?]. Internist (Berl). 1995 Dec;36(12):1117-23.

37. Accad M and Fred HL. Is Jupiter also a God of primary prevention? Texas Heart Institute Journal 2010;37:6-7. PubMed PubMedCentral

38. Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski P, Poole-Wilson PA, Strömberg A, van Veldhuisen DJ, Atar D, Hoes AW, Keren A, Mebazaa A, Nieminen M, Priori SG, Swedberg K; ESC Committee for Practice Guidelines (CPG). The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Develop ed in Collaboration wiht the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM) ESC Guidelines for the Diagnosis and Treatment of Acute and Chronicn Heart Failure. European Heart Journal 2008;29:2388-2442. PubMed CrossRef

39. Hunt SA; American College of Cardiology; American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). J Am Coll Cardiol 2005;46:e1–e82. PubMed CrossRef

40. Williams SC, Schmaltz SP, Morton DJ, Koss RG, Loeb JM Quality of Care in U.S. Hospitals as Reflected by Standardized Measures, 2002–2004 N Engl J Med 2005;353:255-64. PubMed CrossRef

41. Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, Jessup M, Konstam MA, Mancini DM, Michl K, Oates JA, Rahko PS, Silver MA, Stevenson LW, Yancy CW. 2009 Focused update incorporated into the ACC/ AHA 2005 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(14):e391-e479. PubMed CrossRef

42. Jessup M, Abraham WT, Casey DE, Feldman AM, Francis GS, et al. 2009 Writing group to review new evidence and update the 2005 guideline for the management of patients with chronic heart failure writing on behalf of the 2005 Heart Failure Writing Committee. 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 J Am Coll Cardiol 2009;53;1343-1382. CrossRef

43. Dickstein K, Cohen-Solal A, Filippatos G, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology: developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur J Heart Fail 2008;10:933-89.

PubMed CrossRef

44. Swedberg K, Cleland J, Dargie H, et al;Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. Eur Heart J 2005;26:1115-1140. PubMed CrossRef

45. Heart Failure Society of America. Executive summary: HFSA 2006 Comprehensive Heart Failure Practice Guideline. J Card Fail 2006;12:10-38. CrossRef

46. McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Böhm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, Køber L, Lip GY, Maggioni AP, et al. 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. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: Eur J Heart Fail. 2012 Aug;14(8):803-69. PubMed CrossRef

47. Kasje WN, Denig P, de Graeff PA, Haaijer-Ruskamp FM, Perceived barriers for treatment of chronic heart failure in general practice; are they affecting performance? BMC Family Practice 2005,6:19. PubMed PubMedCentral CrossRef

48. Ahmed A, Rich MW, Love TE, et al. Digoxin and reduction in mortality and hospitalization in heart failure: a comprehensive post hoc analysis of the DIG trial. Eur Heart J 2006;27:178-186. PubMed PubMedCentral CrossRef

49. Ahmed A, Allman RM, Fonarow GC, Love TE, Zannad F, et al. Incident Heart Failure Hospitalization and Subsequent Mortality in Chronic Heart Failure: A Propensity-Matched Study. J Cardiac Fail 2008;14:211-218. CrossRef

50. The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991;325:293-302. CrossRef

51. Giamouzis G, Kalogeropoulos A, Georgiopoulou V, Laskar S, Smith AL, Dunbar S, Triposkiadis F, Butler J. Hospitalization epidemic in patients with heart failure: risk factors, risk prediction, knowledge gaps, and future directions. J Card Fail. 2011;17(1):54-75. PubMed CrossRef

52. The CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med 1987;316:1429-1435. CrossRef

53. Macdonald MR, Petrie MC, Varyani F, Ostergren J, Michelson EL, Young JB, Solomon SD, Granger CB, Swedberg K, Yusuf S, Pfeffer MA, McMurray JJ. Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: An analysis of the Candesartan in Heart failure:Assessment of Reduction in Mortality and morbidity (CHARM) programme. Eur Heart J 2008;29:1377-1385. PubMed CrossRef

54. Pfeffer MA, Swedberg K, Granger CB, et al;CHARM Investigators and Committees. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet 2003;362:759-766. PubMed CrossRef

55. Pitt B, Poole-Wilson PA, Segal R, et al. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial–the Losartan Heart Failure Survival Study ELITE II. Lancet 2000;355:1582-1587. PubMed CrossRef

56. Cohn JN, Tognoni G; Valsartan Heart Failure Trial Investigators. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med 2001;345:1667-1675. PubMed CrossRef

57. Flather MD, Shibata MC, Coats AJ, et al;SENIORS Investigators. 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;26:215-225. PubMed CrossRef

58. Beta-Blocker Evaluation of Survival Trial Investigators. A trial of the beta-blocker bucindolol in patients with advanced chronic heart failure. N Engl J Med 2001;344:1659-1667. CrossRef

59. Packer M, Colucci WS, Sackner-Bernstein JD, et al. Doubleblind, placebo-controlled study of the effects of carvedilol in patients with moderate to severe heart failure. The PRECISE Trial. Prospective Randomized Evaluation of Carvedilol on Symptoms and Exercise. Circulation 1996;94(11):2793-2799. PubMed CrossRef

60. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 1999;353:9-13. CrossRef

61. Hjalmarson A, Goldstein S, Fagerberg B, et al. Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure: the Metoprolol CR/XL Randomized Intervention Trial in congestive heart failure (MERIT-HF). MERIT-HF Study Group. JAMA 2000;283:1295-1302. PubMed CrossRef

62. Colucci WS, Packer M, Bristow MR, et al. Carvedilol inhibits clinical progression in patients with mild symptoms of heart failure. US Carvedilol Heart Failure Study Group. Circulation 1996;94:2800-2806. PubMed CrossRef

63. Eichhorn EJ, Bristow MR. The Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial. Curr Control Trials Cardiovasc Med 2001;2:20-23. CrossRef

64. Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999;341:709-717. PubMed CrossRef

65. The Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med 1997;336:525-533. CrossRef

66. Ramani GV, Uber PA, Pharm D, Mehra MR, Chronic Heart Failure Contemporary Diagnosis and Management Mayo Clin Proc. 2010;85(2):180-195).

67. S. Reddy, A. Bahl, and K.K. Talwar Congestive heart failure in Indians: How do we improve diagnosis & management? Indian J Med Res. 2010;132(5):549-560. PubMed PubMedCentral

68. Shibata MC, Nilsson C, Hervas-Malo M, Jacobs P, Tsuyuki RT. Economic implications of treatment guidelines for congestive heart failure. Can J Cardiol. 2005 Dec;21(14):1301-6. PubMed

69. Swedberg K, Komajda M, Bohm M, Borer JS, Ford I, et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomized placebo-controlled study. Eur J Heart Fail. 2010;12:75-81. PubMed CrossRef

70. Willenheimer R, van Veldhuisen DJ, Silke B, et al;CIBIS III Investigators. Effect on survival and hospitalization of initiating treatment for chronic heart failure with bisoprolol followed by enalapril, as compared with the opposite sequence: results of the randomized Cardiac Insufficiency Bisoprolol Study (CIBIS) III. Circulation 2005;112:2426-2435. PubMed CrossRef

71. Cheng JW, Nayar M. A review of heart failure management in the elderly population. Am J Geriatr Pharmacother. 2009;5:233-49. CrossRef

72. Guglin, M Diuretics as pathogenetic treatment for heart failure. International Journal of General Medicine 2011;4:91-98. PubMed PubMedCentral CrossRef

73. Vasan RS, Larson MG, Benjamin EJ, Evans JC, Reiss CK, Levy D. Congestive heart failure in subjects with normal versus reduced left ventricular ejection fraction: Prevalence and mortality in a population based cohort. J Am Coll Cardiol. 1999;33(7):1948-1955. PubMed CrossRef

74. Guglin M. Reappraisal of the role of diuretics in heart failure. Cardiol Rev. 2009;17(2):56-59. PubMed CrossRef

75. Faris RF, Flather M, Purcell H, Poole-Wilson PA, Coats AJ. Diuretics for heart failure. Cochrane Database Syst Rev. 2012 Feb 15;2:CD003838. PubMed

76. Uretsky BF, Young JB, Shahidi FE, Yellen LG, Harrison MC, Jolly MK. Randomized study assessing the effect of digoxin withdrawal in patients with mild to moderate chronic congestive heart failure: results of the PROVED trial. PROVED Investigative Group. J Am Coll Cardiol 1993;22:955-962. PubMed CrossRef

77. Packer M, Gheorghiade M, Young JB, et al. Withdrawal of digoxin from patients with chronic heart failure treated with angiotensin-converting-enzyme inhibitors. RADIANCE Study. N Engl J Med 1993;329:1-7. PubMed CrossRef

78. Young JB, Gheorghiade M, Uretsky BF, Patterson JH, Adams KF Jr. Superiority of “triple” drug therapy in heart failure: insights from the PROVED and RADIANCE trials. Prospective Randomized Study of Ventricular Function and Efficacy of Digoxin. Randomized Assessment of Digoxin and Inhibitors of Angiotensin-Converting Enzyme. J Am Coll Cardiol 1998;32:686-692. PubMed CrossRef

79. Abarquez RF Jr., Ngelangel CA, Sison VM, Morales DD, and Canonigo EB: Digitalis reduces MI and LVH among uncomplicated mild hypertensive industry based cohort in a long term comparative study. American Journal of Hypertension. 8:4, l995.

80. Abarquez RF Jr.: Beyond the Current Paradigm of Managing the Hypertensive Filipino Patient. JAMA, SEA supplement Vol. 2.3;13-19, 1996.

81. Abarquez RF Jr. The old but reliable digitalis: Persistent concerns and expanded indications. Int J Clin Pract 2001: 55(2):108. PubMed

82. Abarquez RF Jr. Management options for hypertension syndrome. Int J Clin Pract 2001;55(8):537-545. PubMed

83. Ahmed A, Pitt B, Rahimtoola SH, Waagstein F, White M, Love TE, Braunwald E. Effects of digoxin at low serum concentrations on mortality and hospitalization in heart failure: a propensity-matched study of the DIG trial. Int J Cardiol. 2008;123:138-146. PubMed PubMedCentral CrossRef

84. Jaarsma T, Haaijer-Ruskamp FM, Sturm H, Van Veldhuisen DJ. Management of heart failure in The Netherlands. European Journal of Heart Failure7 (2005) 371-375. PubMed CrossRef

85. Trochu JN, Gueffet JP. Experience and prospects in the treatment of heart failure. Therapie. 2009;64(2):75-80. PubMed CrossRef

86. Bosch M, Wensing M, Bakx JC, van der Weijden T. Hoes AW, Grol RPTM. Current treatment of chronic heart failure in primary care;still room for improvement. Journal of Evaluation in Clinical Practice 16 (2010)644-650. PubMed

87. Driscoll A, Worrall-Carter L, Hare DL, Davidson PM, Riegel B, Tonkin A, Stewart S. Evidence-based chronic heart-failure management programmes: reality or myth? BMJ Qual Saf. 2011 Jan;20(1):31-7. PubMed CrossRef

88. Mehta PA, McDonagh S, Poole-Wilson PA, Grocott-Mason R, Dubrey SW, Mosterd WL, Rosier PF; Nederlandse Hartstichting; Nederlandse Vereniging voor Cardiologie; Kwaliteitsinstituut voor de Gezondheidzorg CBO. Guidelines in Heart Failure (in Dutch). Ned Tijdschr Geneeskd. 2004;148(13):609-14.

89. Adams KF, Fonarow GC, Emerman CL, LeJemtel TH, Costanzo MR, Abraham WT, et al. Characteristics and outcomes of patients hospitalized for heart failure in the United States: Rationale, design, and preliminary observations from the first 100,000 cases in the Acute Decompensated Heart Failure National Registry (ADHERE). Am Heart J 2005; 149:209 - 216) EuroHeart Failure Survey II (2006) (Nieminen MS, Brutsaert D, Dickstein K, Drexler H, Follath F, Harjola VP, et al. EuroHeart Failure Survey II (EHFS II): A survey on hospitalized acute heart failure patients: Description of population. Eur Heart J 2006;27:2725-2736 CrossRef

90. Tsuchihashi-Makaya M, Kinugawa S, Yokoshiki H, Hamaguchi S, Yokota T, Goto D, Goto K, Takeshita A, Tsutsui H for the JCARE-CARD Investigators Beta-Blocker Use at Discharge in Patients Hospitalized for Heart Failure Is Associated With Improved Survival. Circ J 2010;74:1364-1371. PubMed CrossRef

91. MacKenzie E, Smith A, Angus N, Menzies S, Brulisauer F, Leslie SJ. Mixed-method exploratory study of general practitioner and nurse perceptions of a new community based nurse-led heart failure service. Rural and Remote Health 10:1510. (Online), 2010 http://www.rrh.org.au.

92. Heart Failure clinical guideline. South African Medical Association Heart Failure Working group. S Afr Med J. 1998;88(9 Pt 2):1133-55.

93. Krum H, Jelinek MV, Stewart S, et al. on behalf of the CHF Guidelines Core Writers. Guidelines for the prevention, detection and management ofpeople with chronic heart failure in Australia 2006. MJA 2006;185:549-556. PubMed

94. Arnold JMO, Liu P, et al. Canadian Cardiovascular Society Consensus Conference Recommendations on Heart Failure 2006: Diagnosis and Management. Can J Cardiol;Vol 22 No 1 January 2006.

95. Logeart D, Isnard R, Resche-Rigon M, Seronde MF, de Groote P, Jondeau G, Galinier M, Mulak G, Donal E, Delahaye F, Juilliere Y, Damy T, Jourdain P, Bauer F, Eicher JC, Neuder Y, Trochu JN; on behalf of the working group on Heart Failure of the French Society of Cardiolog. Current aspects of the spectrum of acute heart failure syndromes in a real-life setting: the OFICA study. Eur J Heart Fail first published online November 27, 2012.

96. Califf RM. Translating clinical trials into practice. Tex Heart Inst J 2006;33:192-196. PubMed PubMedCentral

97. Giamouzis G, Kalogeropoulos A, Georgiopoulou V, Laskar S, Smith AL, Dunbar S, Triposkiadis F, Butler J. Hospitalization epidemic in patients with heart failure: risk factors, risk prediction, knowledge gaps, and future directions. J Card Fail. 2011 Jan;17(1):54-75. PubMed CrossRef

98. Eisenstein EL, Yusuf S, Bindal V, Bourassa MG, Horney A, Collins JF, Mark DB; DIG investigators. What is the economic value of digoxin therapy in congestive heart failure patients? Results from the DIG trial. J Card Fail. 2006 Jun;12(5):336-42. PubMed CrossRef

99. Heran BS, Musini VM, Bassett K, Taylor RS, Wright JM; Angiotensin receptor blockers for heart failure Cochrane Database Syst Rev. 2012 Apr 18;4:CD003040.

100. Shaneyfelt, TM, Centor RM, Reassessment of Clinical Practice Guidelines, Go gently into that good night. JAMA 2009.301:868-869 Leykum LK, Parchman M, Pugh J, Lawrence V, Noël PH, McDaniel RR Jr The importance of organizational characteristics for Improving Outcomes in pateitns with chronic disease. A systematic review of congestive heart failure. Implrementation Science 2010;5:66-75.

101. Dobre D, van Jaarsveld CH, de Jongste MJ, Haaijer Ruskamp FM, Ranchor AV The effect of beta-blocker therapy on quality of life in heart failure patients: a systematic review and metaanalysis. Pharmacoepidemiol Drug Saf. 2007 Feb;16(2):152-9. PubMed CrossRef

102. Abdulla J, Køber L, Christensen E, Torp-Pedersen C, Effect of beta-blocker therapy on functional status in patients with heart failure — A meta-analysis European Journal of Heart Failure 8 (2006)522-531. PubMed CrossRef

103. Ezekowitz JA, McAlister FA, Aldosterone blockade and left ventricular dysfunction: a systematic review of randomized clinical trials European Heart Journal (2009) 30,469-477. PubMed

104. Hood WB Jr, Dans AL, Guyatt GH, Jaeschke R, McMurray JJ. Digitalis for treatment of congestive heart failure in patients in sinus rhythm: a systematic review and meta-analysis. J Card Fail. 2004 Apr;10(2):155-64. PubMed CrossRef

105. McKee PA, Castelli WP, McNamara PM, Kannel WB. The natural history of congestive heart failure: the Framingham study. N Engl J Med. 1971 Dec 23;285(26):1441-6. PubMed CrossRef

106. Senni M, Tribouilloy CM, Rodeheffer RJ, Jacobsen SJ, Evans JM, Bailey KR, Redfield MM Congestive heart failure in the community: a study of all incident cases in Olmsted County, Minnesota, in 1991. Circulation. 1998 Nov 24;98(21):2282-9. PubMed CrossRef

107. Jhund PS, Macintyre K, Simpson CR, et al. Long-term trends in first hospitalization for heart failure and subsequent survival between 1986 and 2003: a population study of 5.1 million people. Circulation 2009;119:515-23. PubMed CrossRef

108. John J.V. McMurray, Systolic Heart Failure. N Engl J Med 2010;362:228-38. PubMed CrossRef

109. Ahmed MI, Lainscak M, Mujib M, Love TE, Aban I, Piña IL, Aronow WS, Bittner V, Ahmed A Gender-related dissociation in outcomes in chronic heart failure: reduced mortality but similar hospitalization in women. Int J Cardiol. 2011 Apr 1;148(1):36-42. PubMed PubMedCentral CrossRef

110. Gambassi G, Agha SA, Sui X, Yancy CW, Butler J, Giamouzis G, Love TE, Ahmed A. Race and the natural history of chronic heart failure: a propensity-matched study. J Card Fail. 2008 Jun;14(5):373-8. Epub 2008 May 27. PubMed PubMedCentral CrossRef

111. Ahmed A. A propensity matched study of New York Heart Association class and natural history end points in heart failure. Am J Cardiol. 2007 Feb 15;99(4):549-53. Epub 2006 Dec 28. PubMed PubMedCentral CrossRef

112. Whellan DJ, Hamad ENaturalhistory, adherence, or iatrogenic insult: repeat hospitalizations as a predictor of survival. Am Heart J. 2007;154(2):203-5. PubMed CrossRef

113. Felker GM, Benza RL, Chandler AB, et al. Heart failure etiology and response to milrinone in decompensated heart failure results from the OPTIME-CHF study. J Am Coll Cardiol. 2003;41:997-1003. PubMed CrossRef

114. Erdmann E. Digitalis--friend or foe? Eur Heart J. 1995 Jul;16 Suppl F:16-9.

115. Chatterjee, Kanu. Congestive Heart Failure: What Should Be the Initial Therapy and Why? American Journal of Cardiovascular Drugs: 2002;2(1):1-6. PubMed CrossRef

116. 49 Fitzgerald AA, Powers JD, Ho PM, Maddox TM, Peterson PN, Allen LA, et al. Impact of medication nonadherence on hospitalizations and mortality in heart failure. J Card Fail 2011;17:664-9. PubMed CrossRef

117. Lader E. Review: Eplerenone is not more effective for reducing mortality than other aldosterone antagonists. Ann Intern Med. 2012 Dec 18;157(12):JC6-10. PubMed CrossRef

118. Tevendale E, Baxter J, Heart failure comorbidities at the end of life. Curr Opin Support Palliat Care. 2011 Dec;5(4):322-6. PubMed CrossRef

119. Logeart D, Isnard R, Resche-Rigon M, Seronde MF, de Groote P, Jondeau G, Galinier M, Mulak G, Donal E, Delahaye F, Juilliere Y, Damy T, Jourdain P, Bauer F, Eicher JC, Neuder Y, Trochu JN; on behalf of the working group on Heart Failure of the French Society of Cardiology. Current aspects of the spectrum of acute heart failure syndromes in a real-life setting: the OFICA study. Eur J Heart Fail. 2012 Nov 27. [Epub ahead of print]

120. Dunlay SM, Redfield MM, Weston SA, Therneau TM, Long KH, Shah ND, Roger VL, Hospitalizations After Heart Failure Diagnosis: A Community Perspective. J Am Coll Cardiol. 2009 October 27;54(18):1695-1702. PubMed PubMedCentral CrossRef

121. A comprehensive, longitudinal description of the in-hospital and post-discharge clinical, laboratory, and neurohormonal course of patients with heart failure who die or are rehospitalized within 90 days: analysis from the EVEREST trial. Heart Fail Rev. 2012 May;17(3):485-509.

122. Campbell RT, Jhund PS, Castagno D, Hawkins NM, Petrie MC, McMurray JJV. What Have We Learned About Patients With Heart Failure and Preserved Ejection Fraction From DIGPEF, CHARM-Preserved, and I-PRESERVE? J Am Coll Card l. 2013;60(23);2349-5. CrossRef

123. Smith DH, Johnson ES, Blough DK, Thorp ML, X Petrik AF1 and Crispell KA, Predicting costs of care in heart failure patients. BMC Health Serv Res. 2012;12:434. PubMed PubMedCentral CrossRef

124. Richter B, Koller L, Hohensinner PJ, Zorn G, Brekalo M, Berger R, Mörtl D, Maurer G, Pacher R, Huber K, Wojta J, Hülsmann M, Niessner A. A multi-biomarker risk score improves prediction of long-term mortality in patients with advanced heart failure. Int J Cardiol. 2012 Dec 3. pii: S0167-5273(12)01535-5.

125. Kul S, Barbieri A, Milan E, Montag I, Vanhaecht K, Panella M. Effects of care pathways on the in-hospitaltreatment of heart failure: a systematic review. BMC Cardiovascular Disorders 2012,12:81. PubMed PubMedCentral CrossRef

126 .Hawkins NM, Jhund PS, McMurray JJ, Capewell S. Heart failure and socioeconomic status: accumulating evidence of inequality. Eur J Heart Fail. 2012 Feb;14(2):138-46. PubMed CrossRef

127. Eisenstein EL, Yusuf S, Bindal V, Bourassa MG, Horney A, Collins JF, Mark DB; DIG investigators. What is the economic value of digoxin therapy in congestive heart failure patients? Results from the DIG trial. J Card Fail. 2006 Jun;12(5):336-42. PubMed CrossRef

128. Ahmed A, Waagstein F, Pitt B, White M, Zannad F, Young JB, Rahimtoola SH Effectiveness of Digoxin in Reducing One-Year Mortality in Chronic Heart Failure in the Digitalis Investigation Group Trial. Am J Cardiol. 2009 January 1;103(1):82-87. PubMed PubMedCentral CrossRef

129. Frohlich, ED, The salt conundrum: a hypothesis Hypertension. 2007;50:161-166. PubMed

130. McKelvie RS, Heart Failure, Clin Evid (Online). 2011 Aug 30;2011. pii: 0204.

131. McKelvie, R. Heart Failure Clinical Evidence 2010;02:204-41.

132. Cochrane Collaboration, Research, BMJ 2013;346:f55. CrossRef

133. Faris RF, Flather M, Purcell H, Poole-Wilson PA, Coats AJ. Diuretics for heart failure, Cochrane Database Syst Rev. 2012;15;2.

134. Maeda JL. Evidence-based heart failure performance measures and clinical outcomes: a systematic review. J Card Fail. 2010 May;16(5):411-8. PubMed CrossRef

135. Lew WYW, DeMaria AN. The divergaence between guidelines and practice. J Am Coll Card 2013;61(1):41-3. CrossRef

136. Prog Cardiovasc Nurs. 2009 Dec;24(4):131-40. doi: 10.1111/j.1751-.2009.00051.x. Psychosocial factors, quality of life, and psychological distress: ethnic differences in patients with heart failure. Bean MK1, Gibson D, Flattery M, Duncan A, Hess M.

137. Curr Opin Support Palliat Care. 2007 Dec;1(4):260-6. doi: 10.1097/SPC.0b013e3282f283a3. Psychological, social and spiritual distress at the end of life in heart failure patients.

138. Int J Qual Stud Health Well-being. 2011 Mar 18;6(1). doi: 0.3402/qhw.v6i1.5917. Hope in action-facing cardiac death: A qualitative study of patients with life-threatening disease. Schaufel MA1, Nordrehaug JE, Malterud K.) What can health providers’ hope be?

139. Int J Cardiol. 2015 Dec 1;200:12-4. doi: 10.1016/j.ijcard.2015.05.126. Epub 2015 May 21. Eplerenone in chronic heart failure with depressed systolic function. Volterrani M(1), Iellamo F(2).

140. Cardiovasc Drugs Ther. 2012 Feb 3. Effects of Candesartan on Left Ventricular Function, Aldosterone and BNP in ChronicHeart Failure. Aleksova A1, Masson S, Maggioni AP, Lucci D, Urso R, Staszewsky L, Ciaffoni S, Cacciatore G, Misuraca G, Gulizia M, Mos L, Proietti G, Minneci C, Latini R, Sinagra G; on the behalf of the CandHeart Investigators.

141. Int J Cardiol. 2015 Apr 1;184:163-9. doi: 10.1016/j.ijcard.2015.02.001. Epub 2015 Feb 4. Top ten risk factors for morbidity and mortality in patients with chronic systolic heart failure and elevated heart rate: The SHIFT Risk Model. Ford I1, Robertson M2, Komajda M3, Böhm M4, Borer JS5, Tavazzi L6, Swedberg K7; SHIFT Investigators

142. Int J Cardiol. 2013 Dec 10;170(2):182-8. doi: 10.1016/j.ijcard.2013.10.068. Epub 2013 Oct 25. Clinical profiles and outcomes in patients with chronic heart failure and chronic obstructive pulmonary disease: an efficacy and safety analysis of SHIFT study. Tavazzi L1, Swedberg K, Komajda M, Böhm M, Borer JS, Lainscak M, Robertson M, Ford I; SHIFT Investigators.

143. Eur J Heart Fail. 2015 Sep 30. doi: 10.1002/ejhf.330. [Epub ahead of print] Clinical presentation and outcome by age categories in acute heart failure: results from an international observational cohort. Teixeira A1,2,3, Parenica J4, Park JJ5, Ishihara S6, AlHabib KF7, Laribi S2,3,8, Maggioni A9, Miró Ò10, Sato N6, Kajimoto K11, Cohen-Solal A2,3,12, Fairman E13, Lassus J14, Mueller C15, Peacock WF16, Januzzi JL Jr17, Choi DJ5, Plaisance P2,8, Spinar J4, Mebazaa A1,2,3, Gayat E2,3,18; GREAT (Global Research on Acute Conditions Team) Network.

144. Eur J Heart Fail. 2015 Jun; 17(6):591-600. doi: 10.1002/ejhf.280. Epub 2015 Apr 30. Global variation in clinical profile, management, and post-discharge outcomes among patients hospitalized for worsening chronicheart failure: findings from the ASTRONAUT trial. Greene SJ1, Fonarow GC2, Solomon SD3, Subacius H1, Maggioni AP4, Böhm M5, Lewis EF3, Zannad F6, Gheorghiade M1; ASTRONAUT Investigators and Coordinators.

145. Nieminen MS, Brutsaert D, Dickstein K, et al.: EuroHeart Failure Survey II (EHFS II): a survey on hospitalized acute heart failure patients: description of population. Eur Heart J 2006;27:2725-36. PubMed CrossRef

146.Int J Cardiol. 2013 Sep 20;168(1):458-62. doi: 10.1016/j.ijcard.2012.09.128. Epub 2012 Oct 13. Long-term survival after hospitalization for acute heart failure--differences in prognosis of acutely decompensated chronic and new-onset acute heart failure. Lassus JP1, Siirilä-Waris K, Nieminen MS, Tolonen J, Tarvasmäki T, Peuhkurinen K, Melin J, Pulkki K, Harjola VP; FINN-AKVA study group.

147. Int J Cardiol. 2014 May 1;173(2):163-9. doi: 10.1016/j.ijcard.2014.02.018. Epub 2014 Feb 22. 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. Senni M1, Gavazzi A1, Oliva F2, Mortara A3, Urso R4, Pozzoli M5, Metra M6, Lucci D4, Gonzini L4, Cirrincione V7, Montagna L8, Di Lenarda A9, Maggioni AP10, Tavazzi L5; IN HF Outcome Investigators.

148. Dtsch Arztebl Int. 2015 Apr 24;112(17):298-310. De novo acute heart failure and acutely decompensated chronicheart failure. Hummel A1, Empe K, Dörr M, Felix SB.

149. J Card Fail. 2014 Jul; 20(7):522-32. doi: 10.1016/j.cardfail.2014.04.013. Epub 2014 Apr 18. Can medications be safely withdrawn in patients with stable chronicheart failure? systematic review and meta-analysis. Hopper I1, Samuel R2, Hayward C3, Tonkin A2, Krum H4.

150. Am J Ther. 2009 Jan-Feb; 16(1):5-7. doi: 10.1097/MJT.0b013e31813e6452. Effects of increased dose of diuretics on symptoms, weight, 6-minute walk distance, and echocardiographic measurements of left ventricular systolic and diastolic function in 51 patients with symptomatic heartfailure caused by reduced left ventricular ejection fraction treated with beta blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Kumar A1, Aronow WS, Vadnerkar A, Sivan K, Mittal S.

151. Am Heart J. 2012 Dec;164(6):862-8. doi: 10.1016/j.ahj.2012.08.019. Epub 2012 Oct 29. Effect of admission oral diuretic dose on response to continuous versus bolus intravenous diuretics in acute heartfailure: an analysis from diuretic optimization strategies in acute heartfailure. Shah RV1, McNulty S, O’Connor CM, Felker GM, Braunwald E, Givertz MM.

152. Am J Med. 2015 Jan; 128(1):e17. doi: 10.1016/j.amjmed.2014.03.030. Use of digoxin in chronic systolic heart failure in current era. Temtanakitpaisan Y1, Kilari S2, Damrongwatanasuk R3.

153. Am J Med. 2014 Mar; 127(3):e11. doi: 10.1016/j.amjmed.2013.08.026. The endless story of digitalis. Tavazzi L1.

154. Bourge RC, Fleg JL, Fonarow GC, et al. Digoxin reduces 30- day all-cause hospital admission in older patients with chronic systolic heart failure. Am J Med. 2013;126(8):701-708. PubMed PubMedCentral CrossRef

155. J Am Coll Cardiol. 2014 May 13;63(18):1823-32. doi: 10.1016/j.jacc.2014.01.051. Epub 2014 Mar 5. The use of digoxin in patients with worsening chronic heart failure: reconsidering an old drug to reduce hospital admissions. Ambrosy AP1, Butler J2, Ahmed A3, Vaduganathan M4, van Veldhuisen DJ5, Colucci WS6, Gheorghiade M7.

156. Am J Med. 2014 Jan;127(1):61-70. doi: 10.1016/j.amjmed.2013.08.027. Epub 2013 Nov 18. Digoxin use and lower 30-day all-cause readmission for Medicare beneficiaries hospitalized for heart failure. Ahmed A1, Bourge RC2, Fonarow GC3, Patel K2, Morgan CJ2, Fleg JL4, Aban IB2, Love TE5, Yancy CW6, Deedwania P7, van Veldhuisen DJ8, Filippatos GS9, Anker SD10, Allman RM11.

157. Eur Heart J. 2012 May;33(9):1137-41. doi: 10.1093/ eurheartj/ehs004. Epub 2012 Mar 8. Should we SHIFT our thinking about digoxin? Observations on ivabradine and heart rate reduction in heart failure. Castagno D1, Petrie MC, Claggett B, McMurray J.

158. Eur J Heart Fail. 2013 May; 15(5):551-9. doi: 10.1093/eurjhf/hft010. Epub 2013 Jan 25. Effect of oral digoxin in high-risk heart failure patients: a pre-specified subgroup analysis of the DIG trial. Gheorghiade M1, Patel K, Filippatos G, Anker SD, van Veldhuisen DJ, Cleland JG, Metra M, Aban IB, Greene SJ, Adams KF, McMurray JJ, Ahmed A.

159. J Card Fail. 2013 May; 19(5):295-302. doi: 10.1016/j.cardfail.2013.03.002. Potential effects of digoxin on long-term renal and clinical outcomes in chronic heart failure. Testani JM1, Brisco MA, Tang WH, Kimmel SE, Tiku-Owens A, Forfia PR, Coca SG.

160. Eur J Heart Fail. 2014 May; 16(5):483-93. doi: 10.1002/ ejhf.64. Epub 2014 Feb 23. A perspective on re-evaluating digoxin’s role in the current management of patients with chronic systolic heart failure: targeting serum concentration to reduce hospitalization and improve safety profile. Adams KF Jr1, Ghali JK, Herbert Patterson J, Stough WG, Butler J, Bauman JL, Ventura HO, Sabbah H, Mackowiak JI, van Veldhuisen DJ.

161. Adams KF Jr, Patterson JH, Gattis WA, O’Connor CM, Lee CR, Schwartz TA, Gheorghiade M. Relationship of serum digoxin concentration to mortality and morbidity in women in the digitalis investigation group trial: a retrospective analysis. J Am Coll Cardiol 2005;46:497-50. PubMed CrossRef

162. Ahmed A, Rich MW, Love TE, Lloyd-Jones DM, Aban IB, Colucci WS, Adams KF, Gheorghiade M. Digoxin and reduction in mortality and hospitalization in heart failure: a comprehensive post hoc analysis of the DIG trial. Eur Heart J 2006;27:178-186. PubMed PubMedCentral CrossRef

163. Am J Med. 2015 Jul; 128(7):715-21. doi: 10.1016/j.amjmed.2014.11.036. Epub 2014 Dec 30. Beta-blocker Use and 30-day All-cause Readmission in Medicare Beneficiaries with Systolic Heart Failure. Bhatia V1, Bajaj NS2, Sanam K3, Hashim T3, Morgan CJ3, Prabhu SD2, Fonarow GC4, Deedwania P5, Butler J6, Carson P7, Love TE8, Kheirbek R7, Aronow WS9, Anker SD10, Waagstein F11, Fletcher R7, Allman RM12, Ahmed A7.

164. Am J Cardiovasc Drugs. 2014 Apr; 14(2):101-10. doi: 10.1007/s40256-013-0057-9. Beta-blockers and ivabradine in chronicheart failure: from clinical trials to clinical practice. Di Franco A1, Sarullo FM, Salerno Y, Figliozzi S, Parrinello R, Di Pasquale P, Lanza GA.

165. JACC Heart Fail. 2015 Aug; 3(8):647-53. doi: 10.1016/j.jchf.2015.03.008. Effects of Beta-BlockerWithdrawal in Acute Decompensated Heart Failure: A Systematic Review and Meta-Analysis. Prins KW1, Neill JM2, Tyler JO2, Eckman PM3, Duval S3.

166. Clin Pract. 2013 Nov 4;3(2):e29. doi: 10.4081/cp.2013.e29. eCollection 2013. Comparison between ivabradine and lowdose digoxin in the therapy of diastolic heart failure with preserved left ventricular systolic function. Cocco G1, Jerie P1.

167. Arch Cardiovasc Dis. 2014 Jan;107(1):21-32. doi: 10.1016/j.acvd.2013.11.001. Epub 2013 Dec 30. Prescription of cardiovascular drugs in the French ODIN cohort of heart failure patients according to age and type of chronicheart failure. Juillière Y, Suty-Selton C, Riant E, Darracq JP, Dellinger A, Labarre JP, Druelle J, Mulak G, Danchin N, Jourdain P; ODIN cohort participants.

168. Tex Heart Inst J. 2014 Jun 1;41(3):253-61. doi: 10.14503/THIJ-12-2947. eCollection 2014. Outpatient management of heart failure in the United States, 2006-2008. Mosalpuria K1, Agarwal SK1, Yaemsiri S1, Pierre-Louis B1, Saba S1, Alvarez R1, Russell SD1.

169. Yao DK, Wang LX, Curran S, Ball P Adherence to treatment guidelines in the pharmacological management of chronic heart failure in an Australian population. J Geriatr Cardiol. 2011 Jun;8(2):88-92. PubMed PubMedCentral CrossRef

170. Calvin JE, Shanbhag S, Avery E, Kane J, Richardson D, Powell L. Adherence to evidence-based guidelines for heart failure in physicians and their patients: lessons from the Heart Failure Adherence Retention Trial (HART) Congest Heart Fail. 2012 Mar-Apr;18(2):73-8. PubMed

171. Liu MY, Li YJ, Zhu W, Wei M Effects of intensive clinic follow-up on short-term outcome of outpatients with chronic heart failure. Zhonghua Xin Xue Guan Bing Za Zhi. 2010 Jul;38(7):588-91) If FDT adherence remains inadequate, if not under-dosed in different countries, BPT becomes an essential and indispensable treatment option. What then is standard chronic HF clinical practice management, FDT or BPT only or both?

172. Bertram Pitt et al. The EPHESUS Trial. NEJM 2003;348:1309-1321. CrossRef

173. Gheorghiade et al. Rehospitalization for Heart Failure. JACC Vol. 61, No. 4, January 29, 2013:391-40.

174. Gheorghiade M, Pang PS. Acute heart failure syndromes. J Am Coll Cardiol 2009;53:557-73. PubMed CrossRef

175. J Card Fail. 2014 Jul; 20(7):522-32. doi: 10.1016/ j.cardfail.2014.04.013. Epub 2014 Apr 18. Can medications be safely withdrawn in patients with stable chronic heart failure? systematic review and meta-analysis. Hopper I1, Samuel R, Hayward C3, Tonkin A2, Krum H4.

176. Eur J Heart Fail. 2014 May; 16(5):483-93. doi: 10.1002/ ejhf.64. Epub 2014 Feb 23. A perspective on re-evaluating digoxin’s role in the current management of patients with chronic systolic heart failure: targeting serum concentration to reduce hospitalization and improve safety profile. Adams KF Jr1, Ghali JK, Herbert Patterson J, Stough WG, Butler J, Bauman JL, Ventura HO, Sabbah H, Mackowiak JI, van Veldhuisen DJ.

177. JACC Heart Fail. 2015 Aug; 3(8):647-53. doi: 10.1016/j.jchf.2015.03.008. Effects of Beta-Blocker Withdrawal in Acute Decompensated Heart Failure: A Systematic Review and Meta-Analysis. Prins KW1, Neill JM2, Tyler JO2, Eckman PM3, Duval S3.

178. Bhopal, RS (2008). “Interrelated concepts in the epidemiology of disease: Natural history, spectrum, iceberg, population patterns, and screening”. Concepts of epidemiology: Integrating the ideas, theories, principles, and methods of epidemiology (2nd Ed.). Oxford: Oxford University Press. doi:10.1093/acprof:oso/9780199543144.001.0001. ISBN 9780199543144.CrossRef

179. Clujul Med. 2015;88(1):3-8. doi: 10.15386/cjmed-380. Epub 2015 Jan 28. The Apelin-APJ System in the Evolution of Heart Failure. Goidescu CM1, Vida-Simiti LA.

180 .Eur J Heart Fail. 2013 Jun; 15(6):604-13. doi: 10.1093/ eurjhf/hft062. Epub 2013 Apr 21. How do patients with heart failure with preserved ejection fraction die? Chan MM1, Lam CS.

181. Curr Heart Fail Rep. 2012 Dec;9(4):363-8. doi: 10.1007/s11897-012-0115-7. Comparing new onset heart failure with reduced ejection fraction and new onset heart failure with preserved ejection fraction: an epidemiologic perspective. Brouwers FP1, Hillege HL, van Gilst WH, van Veldhuisen DJ.

182. Patient Educ Couns. 2015 Oct 22. pii: S0738-3991(15)30090-2. doi: 10.1016/j.pec.2015.10.009. [Epub ahead of print] Heart failure family-based education: a systematic review. Srisuk N1, Cameron J2, Ski CF3, Thompson DR.