Acetazolamide
Acetazolamide is a carbonic anhydrase inhibitor and diuretic shown to increase the incidence of successful decongestion when added to a loop diuretic for patients with acute decompensated heart failure, compared to placebo.[69]Mullens W, Dauw J, Martens P, et al. Acetazolamide in acute decompensated heart failure with volume overload. N Engl J Med. 2022 Sep 29;387(13):1185-95.
https://www.nejm.org/doi/10.1056/NEJMoa2203094?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
http://www.ncbi.nlm.nih.gov/pubmed/36027559?tool=bestpractice.com
However, it is not yet in widespread use for this indication, and further data on outcomes and safety are needed.[41]McDonagh TA, Metra M, Adamo M, et al. 2023 Focused update of the 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2023 Oct 1;44(37):3627-39.
https://academic.oup.com/eurheartj/article/44/37/3627/7246292?login=false
http://www.ncbi.nlm.nih.gov/pubmed/37622666?tool=bestpractice.com
Sotaglifozin
Sotagliflozin is a dual sodium-glucose cotransporter-1 (SGLT1)/SGLT2 inhibitor.[70]Cefalo CMA, Cinti F, Moffa S, et al. Sotagliflozin, the first dual SGLT inhibitor: current outlook and perspectives. Cardiovasc Diabetol. 2019 Feb 28;18(1):20.
https://pmc.ncbi.nlm.nih.gov/articles/PMC6393994
http://www.ncbi.nlm.nih.gov/pubmed/30819210?tool=bestpractice.com
It has been approved by the US Food and Drug Administration (FDA) to reduce the risk of cardiovascular death, hospitalisation for heart failure, and urgent heart failure visit in adults with: heart failure; or type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors. It is not approved for use in Europe or the UK as yet.
Tolvaptan
A vasopressin antagonist that blocks the action of arginine vasopressin at the V2 receptor in renal tubules and promotes aquaresis.[1]McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 Sep 21;42(36):3599-726.
https://academic.oup.com/eurheartj/article/42/36/3599/6358045
http://www.ncbi.nlm.nih.gov/pubmed/34447992?tool=bestpractice.com
[71]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://pmc.ncbi.nlm.nih.gov/articles/PMC9574714
http://www.ncbi.nlm.nih.gov/pubmed/35916355?tool=bestpractice.com
[72]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://pmc.ncbi.nlm.nih.gov/articles/PMC6501975
http://www.ncbi.nlm.nih.gov/pubmed/31048435?tool=bestpractice.com
Tolvaptan may be used to treat patients with volume overload and resistant hyponatraemia.[1]McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 Sep 21;42(36):3599-726.
https://academic.oup.com/eurheartj/article/42/36/3599/6358045
http://www.ncbi.nlm.nih.gov/pubmed/34447992?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.[73]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
The European Medicines Agency and the US Food and Drug Administration have approved vericiguat, an orally administered soluble guanylate cyclase stimulator, for treatment of chronic heart failure in patients who are hospitalised for heart failure or need intravenous diuretics. When compared with placebo, it demonstrated a reduced incidence of death from cardiovascular causes or hospitalisation for heart failure in this patient group.[74]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
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.[75]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
[76]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
[77]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
[78]Teerlink JR, Metra M, Felker GM, et al. Relaxin for the treatment of patients with acute heart failure (Pre-RELAX-AHF): a multicentre, randomised, placebo-controlled, parallel-group, dose-finding phase IIb study. Lancet. 2009 Apr 25;373(9673):1429-39.
http://www.ncbi.nlm.nih.gov/pubmed/19329178?tool=bestpractice.com
[79]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.[80]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
[81]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.[81]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 a 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 dyspnoea, or any pre-specified secondary end point when compared with placebo.[82]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