Tolvaptan
A vasopressin antagonist that may relieve symptoms of acute heart failure, but may not reduce morbidity or mortality.[103]Konstam MA, Gheorghiade M, Burnett JC Jr, et al. Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial. JAMA. 2007 Mar 28;297(12):1319-31.
http://jama.ama-assn.org/cgi/content/full/297/12/1319
http://www.ncbi.nlm.nih.gov/pubmed/17384437?tool=bestpractice.com
[104]Shang W, Zhang Y, Han D. Benefits of tolvaptan on early dyspnea relief in patients with acute heart failure: a meta-analysis. Clin Cardiol. 2022 Oct;45(10):995-1001.
https://onlinelibrary.wiley.com/doi/10.1002/clc.23889
http://www.ncbi.nlm.nih.gov/pubmed/35916355?tool=bestpractice.com
[105]Ma G, Ma X, Wang G, et al. Effects of tolvaptan add-on therapy in patients with acute heart failure: meta-analysis on randomised controlled trials. BMJ Open. 2019 May 1;9(4):e025537.
https://bmjopen.bmj.com/content/9/4/e025537
http://www.ncbi.nlm.nih.gov/pubmed/31048435?tool=bestpractice.com
Tolvaptan should be considered for patients with volume overload, hyponatremia (<130 mEq/L), and symptoms of hyponatremia for the short-term correction of hyponatremia and associated symptoms.[36]Ezekowitz JA, O'Meara E, McDonald MA, et al. 2017 comprehensive update of the Canadian Cardiovascular Society guidelines for the management of heart failure. Can J Cardiol. 2017 Nov;33(11):1342-433.
https://www.onlinecjc.ca/article/S0828-282X(17)30973-X/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/29111106?tool=bestpractice.com
Cinepazide
Cinepazide, a vasodilator, was associated with significantly improving symptoms with less adverse effects in patients with decompensated heart failure, compared with dobutamine.[106]Lu Y, Huang D, Dou C, et al. Clinical efficacy of intravenous cinepazide in the treatment of severe decompensated heart failure. Biomedical Research (India). 2012;23(4):561-5.
Vericiguat
Vericiguat is an oral soluble guanylate cyclase stimulator (vasodilator) approved by the Food and Drug Administration for use in adults with symptomatic chronic heart failure and ejection fraction less than 45% (high-risk heart failure), who have recently been hospitalized or received outpatient intravenous diuretics. When compared with placebo, it demonstrated a reduced incidence of death from cardiovascular causes or hospitalization for heart failure in this patient group.[107]Armstrong PW, Pieske B, Anstrom KJ, et al. Vericiguat in patients with heart failure and reduced ejection fraction. N Engl J Med. 2020 May 14;382(20):1883-93.
https://www.nejm.org/doi/10.1056/NEJMoa1915928?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed
http://www.ncbi.nlm.nih.gov/pubmed/32222134?tool=bestpractice.com
Other investigational medications
These include ularitide, tezosentan, istaroxime, perhexiline, relaxin, and cardiac myosin activators. These agents are investigational and not routinely used to treat acute heart failure.[108]De Luca L, Mebazaa A, Filippatos G, et al. Overview of emerging pharmacologic agents for acute heart failure syndromes. Eur J Heart Fail. 2008 Feb;10(2):201-13.
http://onlinelibrary.wiley.com/doi/10.1016/j.ejheart.2008.01.002/full
http://www.ncbi.nlm.nih.gov/pubmed/18279775?tool=bestpractice.com
[109]De Luca L, Fonarow GC, Mebazaa A, et al. Early pharmacological treatment of acute heart failure syndromes: a systematic review of clinical trials. Acute Card Care. 2007;9(1):10-21.
http://www.ncbi.nlm.nih.gov/pubmed/17453534?tool=bestpractice.com
[110]deGoma EM, Vagelos RH, Fowler MB, et al. Emerging therapies for the management of decompensated heart failure: from bench to bedside. J Am Coll Cardiol. 2006 Dec 19;48(12):2397-409.
http://www.ncbi.nlm.nih.gov/pubmed/17174176?tool=bestpractice.com
[111]Teerlink JR, Davison BA, Cotter G, et al. Effects of serelaxin in patients admitted for acute heart failure: a meta-analysis. Eur J Heart Fail. 2020 Feb;22(2):315-29.
https://onlinelibrary.wiley.com/doi/10.1002/ejhf.1692
http://www.ncbi.nlm.nih.gov/pubmed/31886953?tool=bestpractice.com
Adenosine A1- receptor antagonists (e.g., tonapofylline and rolofylline) have failed to show any clinical benefit in initial studies.[112]Ensor CR, Russell SD. Tonapofylline: a selective adenosine-1 receptor antagonist for the treatment of heart failure. Expert Opin Pharmacother. 2010 Oct;11(14):2405-15.
http://www.ncbi.nlm.nih.gov/pubmed/20807184?tool=bestpractice.com
[113]Massie BM, O'Connor CM, Metra M, et al. Rolofylline, an adenosine A1-receptor antagonist, in acute heart failure. N Engl J Med. 2010 Oct 7;363(15):1419-28.
http://www.nejm.org/doi/full/10.1056/NEJMoa0912613#t=articleTop
http://www.ncbi.nlm.nih.gov/pubmed/20925544?tool=bestpractice.com
When compared with placebo, rolofylline did not show any benefit in patients with acute heart failure and impaired renal function.[113]Massie BM, O'Connor CM, Metra M, et al. Rolofylline, an adenosine A1-receptor antagonist, in acute heart failure. N Engl J Med. 2010 Oct 7;363(15):1419-28.
http://www.nejm.org/doi/full/10.1056/NEJMoa0912613#t=articleTop
http://www.ncbi.nlm.nih.gov/pubmed/20925544?tool=bestpractice.com
In one phase 2 trial of patients with acute heart failure (ejection fraction ≤40%), treatment with omecamtiv mecarbil (a selective small-molecule activator of cardiac myosin) did not improve the primary end point of dyspnea, or any prespecified secondary end point when compared with placebo.[114]Teerlink JR, Felker GM, McMurray JJ, et al; ATOMIC-AHF Investigators. 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):1444-55.
http://www.sciencedirect.com/science/article/pii/S073510971600351X
http://www.ncbi.nlm.nih.gov/pubmed/27012405?tool=bestpractice.com