Where are we in 2021 with heart failure with reduced ejection fraction?—current outlook and expectations from new promising clinical trials

Figures

• 

  Fig. 1. Historical timeline of breakthrough clinical trials for heart failure with reduced ejection fraction

• 

  Fig. 2. Pathways of synthesis and release of B-type natriuretic peptide and a pivotal role of cyclic guanosine monophosphate pathway modulation with sacubitril and vericiguat in heart failure outcome [9–11]. BNP B-type natriuretic peptide, cGMP cyclic guanosine monophosphate, GC guanyl cyclase, GTP guanosine triphosphate, NPPB natriuretic peptide B, NPRA natriuretic peptide receptor A, NT-proBNP N-terminal prohormone of BNP, pGC particulate guanylate cyclase, sGC soluble guanylate cyclase

• 

  Fig. 3. Mechanism of action of sodium‐glucose co‐transporter inhibitors [16, 17]. Glc glucose, GLUT1 glucose transporter 1, GLUT2 glucose transporter 2, K+ potassium, Na+ sodium, SGLT1 sodium‐glucose co‐transporter 1, SGLT2 sodium‐glucose co‐transporter 2

• 

  Fig. 4. Suggests therapeutic algorithm for a patient with symptomatic heart failure with reduced ejection fraction including administration of novel drugs. Green indicates a class I recommendation; yellow indicates a class IIa recommendation; blue indicates proposed therapy (4, 36, 37). aNYHA class II-IV, bLVEF < 40%, cbeta-blocker is recommended, dif not contraindicated, eCRT is recommended if QRS ≥ 130 ms and LBBB (in sinus rhythm), fCRT should/may be considered if QRS ≥ 130 ms with non-LBBB (in a sinus rhythm) or for patients in AF provided a strategy to ensure bi-ventricular pacing. AF atrial fibrillation, ARNI angiotensin receptor/neprilysin inhibitor, bpm beats per minute, CRT cardiac resynchronization therapy, eGFR estimated glomerular filtration rate, HFrEF heart failure with reduced ejection fraction, H-ISDN hydralazine–isosorbide dinitrate, HR heart rate, ICD implantable cardioverter-defibrillator, LBBB left bundle branch block, LVAD left ventricle assist device, LVEF left ventricle ejection fraction, MR mineralocorticoid receptor, NYHA New York Heart Association, OMT optimal medical therapy, SBP systolic blood pressure, SGLT2 sodium-glucose co-transporter-2, VT/VF ventricular…