New developments in the pharmacotherapeutic management of heart failure in elderly patients: concerns and considerations

References

• Lloyd-Jones DM, Larson MG, Leip EP, et al. Lifetime risk for developing congestive heart failure: the Framingham Heart Study. Circulation. 2002 Dec 10;106(24):3068–3072.
   PubMed Web of Science ®Google Scholar
• Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2016 Aug;18(8):891–975.
   PubMed Web of Science ®Google Scholar
• Kraai IH, Vermeulen KM, Hillege HL, et al. Perception of impairments by patients with heart failure. Eur J Cardiovasc Nurs. 2016 Apr;15(2):178–185.
   PubMed Web of Science ®Google Scholar
• Krumholz HM, Merrill AR, Schone EM, et al. Patterns of hospital performance in acute myocardial infarction and heart failure 30-day mortality and readmission. Circ Cardiovasc Qual Outcomes. 2009 Sep;2(5):407–413.
   PubMed Web of Science ®Google Scholar
• Zuckerman RB, Sheingold SH, Orav EJ, et al. Readmissions, observation, and the hospital readmissions reduction program. N Engl J Med. 2016 Apr 21;374(16):1543–1551.
   PubMed Web of Science ®Google Scholar
• Heidenreich PA, Albert NM, Allen LA, et al. Forecasting the impact of heart failure in the united states: A policy statement from the american heart association. Circ Heart Fail. 2013 May;6(3):606–619.
   PubMed Web of Science ®Google Scholar
• Active Ageing: A Policy Framework. World Health Organization, 2002. Available from: http://apps.who.int/iris/bitstream/10665/67215/1/WHO_NMH_NPH_02.8.pdf [Last accessed 15 December 2016].
   Google Scholar
• World Population Ageing. World Health Organization, 2015. Available from: http://www.un.org/en/development/desa/population/publications/pdf/ageing/WPA2015_Report.pdf [Last accessed 15 December 2016].
   Google Scholar
• Haldeman GA, Croft JB, Giles WH, et al. Hospitalization of patients with heart failure: national hospital discharge survey, 1985 to 1995. Am Heart J. 1999 Feb;137(2):352–360.
   PubMed Web of Science ®Google Scholar
• Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics-2016 update: A report from the American Heart Association. Circulation. 2016 Jan 26;133(4):e38–360.
   PubMed Web of Science ®Google Scholar
• Strait JB, Lakatta EG. Aging-associated cardiovascular changes and their relationship to heart failure. Heart Fail Clin. 2012 Jan;8(1):143–164.
   PubMed Web of Science ®Google Scholar
• Khatibzadeh S, Farzadfar F, Oliver J, et al. Worldwide risk factors for heart failure: A systematic review and pooled analysis. Int J Cardiol. 2013 Sep 30;168(2):1186–1194.
   PubMed Web of Science ®Google Scholar
• 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 Feb 3;119(4):515–523.
   PubMed Web of Science ®Google Scholar
• Heidenreich PA, Trogdon JG, Khavjou OA, et al. Forecasting the future of cardiovascular disease in the united states: A policy statement from the American Heart Association. Circulation. 2011 Mar 1;123(8):933–944.
   PubMed Web of Science ®Google Scholar
• Van Riet EE, Hoes AW, Wagenaar KP, et al. Epidemiology of heart failure: the prevalence of heart failure and ventricular dysfunction in older adults over time A systematic review. Eur J Heart Fail. 2016 Mar;18(3):242–252.
   PubMed Web of Science ®Google Scholar
• Braunstein JB, Anderson GF, Gerstenblith G, et al. Noncardiac comorbidity increases preventable hospitalizations and mortality among medicare beneficiaries with chronic heart failure. J Am Coll Cardiol. 2003 Oct 1;42(7):1226–1233.
   PubMed Web of Science ®Google Scholar
• Wong CY, Chaudhry SI, Desai MM, et al. Trends in comorbidity, disability, and polypharmacy in heart failure. Am J Med. 2011 Feb;124(2):136–143.
   PubMed Web of Science ®Google Scholar
• Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007 Nov 15;357(20):2001–2015.
   PubMed Web of Science ®Google Scholar
• Roe MT, Armstrong PW, Fox KA, et al. Prasugrel versus clopidogrel for acute coronary syndromes without revascularization. N Engl J Med. 2012 Oct 4;367(14):1297–1309.
   PubMed Web of Science ®Google Scholar
• Shah SJ, Katz DH, Deo RC. Phenotypic spectrum of heart failure with preserved ejection fraction. Heart Fail Clin. 2014 Jul;10(3):407–418.
   PubMed Web of Science ®Google Scholar
• Fischer M, Baessler A, Hense HW, et al. Prevalence of left ventricular diastolic dysfunction in the community Results from a doppler echocardiographic-based survey of a population sample. Eur Heart J. 2003 Feb;24(4):320–328.
   PubMed Web of Science ®Google Scholar
• Klapholz M, Maurer M, Lowe AM, et al. Hospitalization for heart failure in the presence of a normal left ventricular ejection fraction: results of the New York Heart Failure Registry. J Am Coll Cardiol. 2004 Apr 21;43(8):1432–1438.
   PubMed Web of Science ®Google Scholar
• Martinez-Brana L, Mateo-Mosquera L, Bermudez-Ramos M, et al. Clinical characteristics and prognosis of heart failure in elderly patients. Rev Port Cardiol. 2015 Jul-Aug;34(7–8):457–463.
   PubMedGoogle Scholar
• Lam CS, Solomon SD. The middle child in heart failure: heart failure with mid-range ejection fraction (40-50%). Eur J Heart Fail. 2014 Oct;16(10):1049–1055.
   PubMed Web of Science ®Google Scholar
• Savarese G, Musella F, D’Amore C, et al. Changes of natriuretic peptides predict hospital admissions in patients with chronic heart failure: A meta-analysis. JACC Heart Fail. 2014 Apr;2(2):148–158.
   PubMed Web of Science ®Google Scholar
• deFilippi CR, De Lemos JA, Christenson RH, et al. Association of serial measures of cardiac troponin T using a sensitive assay with incident heart failure and cardiovascular mortality in older adults. JAMA. 2010 Dec 8;304(22):2494–2502.
   PubMed Web of Science ®Google Scholar
• Van Veldhuisen DJ, Linssen GC, Jaarsma T, et al. B-type natriuretic peptide and prognosis in heart failure patients with preserved and reduced ejection fraction. J Am Coll Cardiol. 2013 Apr 9;61(14):1498–1506.
   PubMed Web of Science ®Google Scholar
• Brouwers FP, De Boer RA, Van Der Harst P, et al. 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 May;34(19):1424–1431.
   PubMed Web of Science ®Google Scholar
• Wang TJ, Wollert KC, Larson MG, et al. Prognostic utility of novel biomarkers of cardiovascular stress: the Framingham Heart Study. Circulation. 2012 Sep 25;126(13):1596–1604.
   PubMed Web of Science ®Google Scholar
• Meijers WC, De Boer RA, Van Veldhuisen DJ, et al. Biomarkers and low risk in heart failure. Data from COACH and TRIUMPH. Eur J Heart Fail. 2015 Dec;17(12):1271–1282.
   PubMed Web of Science ®Google Scholar
• Huelsmann M, Neuhold S, Resl M, et al. PONTIAC (NT-proBNP selected prevention of cardiac events in a population of diabetic patients without a history of cardiac disease): A prospective randomized controlled trial. J Am Coll Cardiol. 2013 Oct 8;62(15):1365–1372.
   PubMed Web of Science ®Google Scholar
• Ledwidge M, Gallagher J, Conlon C, et al. Natriuretic peptide-based screening and collaborative care for heart failure: the STOP-HF randomized trial. JAMA. 2013 Jul 3;310(1):66–74.
   PubMed Web of Science ®Google Scholar
• Meijers WC, De Boer RA, Ho JE. Biomarkers to identify and prevent new-onset heart failure in the community. Eur J Heart Fail. 2016 Nov;18(11):1351–1352.
   PubMed Web of Science ®Google Scholar
• Brouwers FP, Van Gilst WH, Damman K, et al. Clinical risk stratification optimizes value of biomarkers to predict new-onset heart failure in a community-based cohort. Circ Heart Fail. 2014 Sep;7(5):723–731.
   PubMed Web of Science ®Google Scholar
• De Boer RA, Daniels LB, Maisel AS, et al. State of the art: newer biomarkers in heart failure. Eur J Heart Fail. 2015 Jun;17(6):559–569.
   PubMed Web of Science ®Google Scholar
• Meijers WC, Van Der Velde AR, De Boer RA. Biomarkers in heart failure with preserved ejection fraction. Neth Heart J. 2016 Apr;24(4):252–258.
   PubMed Web of Science ®Google Scholar
• De Boer RA, Edelmann F, Cohen-Solal A, et al. Galectin-3 in heart failure with preserved ejection fraction. Eur J Heart Fail. 2013 Oct;15(10):1095–1101.
   PubMed Web of Science ®Google Scholar
• Meijers WC, Van Der Velde AR, De Boer RA. ST2 and galectin-3: ready for prime time? EJIFCC. 2016 Aug 1;27(3):238–252.
   PubMedGoogle Scholar
• Santhanakrishnan R, Chong JP, Ng TP, et al. Growth differentiation factor 15, ST2, high-sensitivity troponin T, and N-terminal pro brain natriuretic peptide in heart failure with preserved vs. reduced ejection fraction. Eur J Heart Fail. 2012 Dec;14(12):1338–1347.
   PubMed Web of Science ®Google Scholar
• Cleland JG, Tendera M, Adamus J, et al. The perindopril in elderly people with chronic heart failure (PEP-CHF) study. Eur Heart J. 2006 Oct;27(19):2338–2345.
   PubMed Web of Science ®Google Scholar
• Massie BM, Carson PE, McMurray JJ, et al. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med. 2008 Dec 4;359(23):2456–2467.
   PubMed Web of Science ®Google Scholar
• Hernandez AF, Hammill BG, O’Connor CM, et al. 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 Jan 13;53(2):184–192.
   PubMed Web of Science ®Google Scholar
• 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 Aug 1;114(5):397–403.
   PubMed Web of Science ®Google Scholar
• 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 Jun 9;53(23):2150–2158.
   PubMed Web of Science ®Google Scholar
• Haass M, Kitzman DW, Anand IS, et al. Body mass index and adverse cardiovascular outcomes in heart failure patients with preserved ejection fraction: results from the irbesartan in heart failure with preserved ejection fraction (I-PRESERVE) trial. Circ Heart Fail. 2011 May;4(3):324–331.
   PubMed Web of Science ®Google Scholar
• Kenchaiah S, Evans JC, Levy D, et al. Obesity and the risk of heart failure. N Engl J Med. 2002 Aug 1;347(5):305–313.
   PubMed Web of Science ®Google Scholar
• Morkedal B, Vatten LJ, Romundstad PR, et al. Risk of myocardial infarction and heart failure among metabolically healthy but obese individuals: HUNT (nord-trondelag health study), Norway. J Am Coll Cardiol. 2014 Mar 25;63(11):1071–1078.
   PubMed Web of Science ®Google Scholar
• Kitzman DW, Brubaker P, Morgan T, et al. Effect of caloric restriction or aerobic exercise training on peak oxygen consumption and quality of life in obese older patients with heart failure with preserved ejection fraction: A randomized clinical trial. JAMA. 2016 Jan 5;315(1):36–46.
   PubMed Web of Science ®Google Scholar
• Lien CT, Gillespie ND, Struthers AD, et al. Heart failure in frail elderly patients: diagnostic difficulties, co-morbidities, polypharmacy and treatment dilemmas. Eur J Heart Fail. 2002 Jan;4(1):91–98.
   PubMed Web of Science ®Google Scholar
• Vazir A, Solomon SD. Management strategies for heart failure with preserved ejection fraction. Heart Fail Clin. 2014 Oct;10(4):591–598.
   PubMed Web of Science ®Google Scholar
• Gheorghiade M, Abraham WT, Albert NM, et al. Systolic blood pressure at admission, clinical characteristics, and outcomes in patients hospitalized with acute heart failure. JAMA. 2006 Nov 8;296(18):2217–2226.
   Google Scholar
• Herrera AP, Snipes SA, King DW, et al. Disparate inclusion of older adults in clinical trials: priorities and opportunities for policy and practice change. Am J Public Health. 2010 Apr 1;100(Suppl 1):S105–12.
   PubMedGoogle Scholar
• 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). the CONSENSUS trial study group. N Engl J Med. 1987 Jun 4;316:(23)1429–1435.
   PubMed Web of Science ®Google Scholar
• Pfeffer MA, Swedberg K, Granger CB, et al. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-overall programme. Lancet. 2003 Sep 6;362(9386):759–766.
   PubMed Web of Science ®Google Scholar
• Pitt B, Segal R, Martinez FA, et al. Randomised trial of losartan versus captopril in patients over 65 with heart failure (evaluation of losartan in the elderly study, ELITE). Lancet. 1997 Mar 15;349(9054):747–752.
   PubMed Web of Science ®Google Scholar
• 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 May 6;355(9215):1582–1587.
   PubMed Web of Science ®Google Scholar
• 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 Oct 20;380(9851):1387–1395.
   PubMed Web of Science ®Google Scholar
• McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014 Sep 11;371(11):993–1004.
   PubMed Web of Science ®Google Scholar
• Jhund PS, Fu M, Bayram E, et al. Efficacy and safety of LCZ696 (sacubitril-valsartan) according to age: insights from PARADIGM-HF. Eur Heart J. 2015 Oct 7;36(38):2576–2584.
   PubMed Web of Science ®Google Scholar
• Williams B, Cockcroft JR, Kario K, et al. Rationale and study design of the prospective comparison of angiotensin receptor neprilysin inhibitor with angiotensin receptor blocker MEasuring arterial sTiffness in the eldERly (PARAMETER) study. BMJ Open. 2014 Feb 4;4(2):e004254,2013–004254.
   Google Scholar
• Williams B, Cockcroft JR, Kario K, et al. Effects of Sacubitril/Valsartan versus olmesartan on central hemodynamics in the elderly with systolic hypertension: the PARAMETER study. Hypertension. 2017 Mar;69(3):411–420.
   PubMed Web of Science ®Google Scholar
• O’Connor CM, Gattis WA, Uretsky BF, et al. Continuous intravenous dobutamine is associated with an increased risk of death in patients with advanced heart failure: insights from the Flolan International Randomized Survival Trial (FIRST). Am Heart J. 1999 Jul;138(1 Pt 1):78–86.
   PubMed Web of Science ®Google Scholar
• Cohn JN, Goldstein SO, Greenberg BH, et al. A dose-dependent increase in mortality with vesnarinone among patients with severe heart failure. Vesnarinone Trial Investigators. N Engl J Med. 1998 Dec 17;339(25):1810–1816.
   PubMed Web of Science ®Google Scholar
• Packer M, Carver JR, Rodeheffer RJ, et al. Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE study research group. N Engl J Med. 1991 Nov 21;325(21):1468–1475.
   PubMed Web of Science ®Google Scholar
• Packer M, Colucci W, Fisher L, et al. Effect of levosimendan on the short-term clinical course of patients with acutely decompensated heart failure. JACC Heart Fail. 2013 Apr;1(2):103–111.
   PubMed Web of Science ®Google Scholar
• Krell MJ, Kline EM, Bates ER, et al. Intermittent, ambulatory dobutamine infusions in patients with severe congestive heart failure. Am Heart J. 1986 Oct;112(4):787–791.
   PubMed Web of Science ®Google Scholar
• Malik FI, Hartman JJ, Elias KA, et al. Cardiac myosin activation: A potential therapeutic approach for systolic heart failure. Science. 2011 Mar 18;331(6023):1439–1443.
   PubMed Web of Science ®Google Scholar
• Teerlink JR, Clarke CP, Saikali KG, et al. Dose-dependent augmentation of cardiac systolic function with the selective cardiac myosin activator, omecamtiv mecarbil: A first-in-man study. Lancet. 2011 Aug 20;378(9792):667–675.
   PubMed Web of Science ®Google Scholar
• Cleland JG, Teerlink JR, Senior R, et al. The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure: A double-blind, placebo-controlled, crossover, dose-ranging phase 2 trial. Lancet. 2011 Aug 20;378(9792):676–683.
   PubMed Web of Science ®Google Scholar
• Teerlink JR, Felker GM, McMurray JJ, et al. Acute treatment with omecamtiv mecarbil to increase contractility in acute heart failure: the ATOMIC-AHF study. J Am Coll Cardiol. 2016 Mar 29;67(12):1444–1455.
   PubMed Web of Science ®Google Scholar
• Teerlink JR, Felker GM, McMurray JJ, et al. Chronic oral study of myosin activation to increase contractility in heart failure (COSMIC-HF): A phase 2, pharmacokinetic, randomised, placebo-controlled trial. Lancet. 2016 Dec 10;388(10062):2895–2903.
   PubMed Web of Science ®Google Scholar
• 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 Jul 23;62(4):263–271.
   PubMed Web of Science ®Google Scholar
• Stasch JP, Schmidt PM, Nedvetsky PI, et al. Targeting the heme-oxidized nitric oxide receptor for selective vasodilatation of diseased blood vessels. J Clin Invest. 2006 Sep;116(9):2552–2561.
   PubMed Web of Science ®Google Scholar
• Greene SJ, Gheorghiade M, Borlaug BA, et al. The cGMP signaling pathway as a therapeutic target in heart failure with preserved ejection fraction. J Am Heart Assoc. 2013 Dec 11;2(6):e000536.
   PubMed Web of Science ®Google Scholar
• Dubin RF, Shah SJ. Soluble guanylate cyclase stimulators: A novel treatment option for heart failure associated with cardiorenal syndromes? Curr Heart Fail Rep. 2016 Jun;13(3):132–139.
   PubMedGoogle Scholar
• Pieske B, Butler J, Filippatos G, et al. Rationale and design of the SOluble guanylate cyclase stimulatoR in heArT failurE studies (SOCRATES). Eur J Heart Fail. 2014 Sep;16(9):1026–1038.
   PubMed Web of Science ®Google Scholar
• Gheorghiade M, Greene SJ, Butler J, et al. Effect of vericiguat, a soluble guanylate cyclase stimulator, on natriuretic peptide levels in patients with worsening chronic heart failure and reduced ejection fraction: the SOCRATES-REDUCED randomized trial. JAMA. 2015 Dec 1;314(21):2251–2262.
   PubMed Web of Science ®Google Scholar
• Bohm M, Swedberg K, Komajda M, et al. Heart rate as a risk factor in chronic heart failure (SHIFT): the association between heart rate and outcomes in a randomised placebo-controlled trial. Lancet. 2010 Sep 11;376(9744):886–894.
   PubMed Web of Science ®Google Scholar
• Oliphant CS, Owens RE, Bolorunduro OB, et al. Ivabradine: A review of labeled and off-label uses. Am J Cardiovasc Drugs. 2016 Oct;16(5):337–347.
   PubMed Web of Science ®Google Scholar
• Swedberg K, Komajda M, Bohm M, et al. Ivabradine and outcomes in chronic heart failure (SHIFT): A randomised placebo-controlled study. Lancet. 2010 Sep 11;376(9744):875–885.
   PubMed Web of Science ®Google Scholar
• Fox K, Ford I, Steg PG, et al. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): A randomised, double-blind, placebo-controlled trial. Lancet. 2008 Sep 6;372(9641):807–816.
   PubMed Web of Science ®Google Scholar
• Fox K, Ford I, Steg PG, et al. Ivabradine in stable coronary artery disease without clinical heart failure. N Engl J Med. 2014 Sep 18;371(12):1091–1099.
   PubMed Web of Science ®Google Scholar
• Kosmala W, Holland DJ, Rojek A, et al. 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 Oct 8;62(15):1330–1338.
   PubMed Web of Science ®Google Scholar
• Pal N, Sivaswamy N, Mahmod M, et al. Effect of selective heart rate slowing in heart failure with preserved ejection fraction. Circulation. 2015 Nov 3;132(18):1719–1725.
   PubMed Web of Science ®Google Scholar
• Weber KT. Aldosterone in congestive heart failure. N Engl J Med. 2001 Dec 6;345(23):1689–1697.
   PubMed Web of Science ®Google Scholar
• Pitt B, Pedro Ferreira J, Zannad F. Mineralocorticoid receptor antagonists in patients with heart failure: current experience and future perspectives. Eur Heart J Cardiovasc Pharmacother. 2017;3(1):48–57.
   PubMed Web of Science ®Google Scholar
• Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999 Sep 2;341(10):709–717.
   PubMed Web of Science ®Google Scholar
• Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003 Apr 3;348(14):1309–1321.
   PubMed Web of Science ®Google Scholar
• Zannad F, McMurray JJ, Drexler H, et al. Rationale and design of the Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure (EMPHASIS-HF). Eur J Heart Fail. 2010 Jun;12(6):617–622.
   PubMed Web of Science ®Google Scholar
• Zannad F, McMurray JJ, Krum H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011 Jan 6;364(1):11–21.
   PubMed Web of Science ®Google Scholar
• 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 Feb 27;309(8):781–791.
   PubMed Web of Science ®Google Scholar
• Pitt B, Pfeffer MA, Assmann SF, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014 Apr 10;370(15):1383–1392.
   PubMed Web of Science ®Google Scholar
• Pfeffer MA, Claggett B, Assmann SF, et al. Regional variation in patients and outcomes in the treatment of preserved cardiac function heart failure with an aldosterone antagonist (TOPCAT) trial. Circulation. 2015 Jan 6;131(1):34–42.
   PubMed Web of Science ®Google Scholar
• Jain N, Kotla S, Little BB, et al. Predictors of hyperkalemia and death in patients with cardiac and renal disease. Am J Cardiol. 2012 May 15;109(10):1510–1513.
   PubMed Web of Science ®Google Scholar
• Rosa RM, Silva P, Young JB, et al. Adrenergic modulation of extrarenal potassium disposal. N Engl J Med. 1980 Feb 21;302(8):431–434.
   PubMed Web of Science ®Google Scholar
• Acker CG, Johnson JP, Palevsky PM, et al. Hyperkalemia in hospitalized patients: causes, adequacy of treatment, and results of an attempt to improve physician compliance with published therapy guidelines. Arch Intern Med. 1998 Apr 27;158(8):917–924.
   PubMedGoogle Scholar
• Dinsdale C, Wani M, Steward J, et al. Tolerability of spironolactone as adjunctive treatment for heart failure in patients over 75 years of age. Age Ageing. 2005 Jul;34(4):395–398.
   PubMed Web of Science ®Google Scholar
• Chaaban A, Abouchacra S, Gebran N, et al. Potassium binders in hemodialysis patients: A friend or foe? Ren Fail. 2013;35(2):185–188.
   PubMed Web of Science ®Google Scholar
• Vu BN, De Castro AM, Shottland D, et al. Patiromer: the first potassium binder approved in over 50 years. Cardiol Rev. 2016 Nov/Dec;24(6):316–323.
   PubMed Web of Science ®Google Scholar
• Pitt B, Anker SD, Bushinsky DA, et al. Evaluation of the efficacy and safety of RLY5016, a polymeric potassium binder, in a double-blind, placebo-controlled study in patients with chronic heart failure (the PEARL-HF) trial. Eur Heart J. 2011 Apr;32(7):820–828.
   PubMed Web of Science ®Google Scholar
• Moss AJ, Hall WJ, Cannom DS, et al. Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med. 2009 Oct 1;361(14):1329–1338.
   PubMed Web of Science ®Google Scholar
• Schmitto JD, Hanke JS, Rojas SV, et al. First implantation in man of a new magnetically levitated left ventricular assist device (HeartMate III). J Heart Lung Transplant. 2015 Jun;34(6):858–860.
   PubMed Web of Science ®Google Scholar
• Aaronson KD, Slaughter MS, Miller LW, et al. Use of an intrapericardial, continuous-flow, centrifugal pump in patients awaiting heart transplantation. Circulation. 2012 Jun 26;125(25):3191–3200.
   PubMed Web of Science ®Google Scholar
• Lund LH, Edwards LB, Kucheryavaya AY, et al. The registry of the international society for heart and lung transplantation: thirty-second official adult heart transplantation report–2015; focus theme: early graft failure. J Heart Lung Transplant. 2015 Oct;34(10):1244–1254.
   PubMed Web of Science ®Google Scholar
• Mukete BN, Ferdinand KC. Polypharmacy in older adults with hypertension: A comprehensive review. J Clin Hypertens (Greenwich). 2016 Jan;18(1):10–18.
   PubMed Web of Science ®Google Scholar
• Davies DF, Shock NW. Age changes in glomerular filtration rate, effective renal plasma flow, and tubular excretory capacity in adult males. J Clin Invest. 1950 May;29(5):496–507.
   PubMed Web of Science ®Google Scholar
• Longhini C, Molino C, Fabbian F. Cardiorenal syndrome: still not a defined entity. Clin Exp Nephrol. 2010 Feb;14(1):12–21.
   PubMed Web of Science ®Google Scholar
• Vu T, Ma P, Xiao JJ, et al. Population pharmacokinetic-pharmacodynamic modeling of omecamtiv mecarbil, a cardiac myosin activator, in healthy volunteers and patients with stable heart failure. J Clin Pharmacol. 2015 Nov;55(11):1236–1247.
   PubMed Web of Science ®Google Scholar
• Greenberg BH, Chou W, Saikali KG, et al. Safety and tolerability of omecamtiv mecarbil during exercise in patients with ischemic cardiomyopathy and angina. JACC Heart Fail. 2015 Jan;3(1):22–29.
   PubMed Web of Science ®Google Scholar