Practical recommendations: summary

1	Recommendations on the use of biomarkers for the diagnosis of HF
	BNP and NT-proBNP are used for heart failure diagnosis and prognosis, but renal dysfunction may affect results and there is no evidence to target treatment to specific levels. NTproBNP is the more accurate biomarker in patients on sacubitril/valsartan.
2	Recommendation on imaging for diagnosis and follow-up of HF patients
	Patients with new HF should have an echocardiogram (with strain imaging if available) to aid in the correct diagnosis and after 3–6 months of GDMT, repeat imaging can help in treatment decisions, with alternative modalities like cardiac MRI considered if echocardiography fails to assess LVEF.
3	Recommendation on initiation, addition, or switching to new evidence-based guideline-directed therapy for HFrEF and its titration
	Established treatments for HFrEF include ARNIs, SGLT2i, ACEIs, ARBs, beta-blockers, aldosterone antagonists, loop diuretics, hydralazine/isosorbide dinitrate, and ivabradine, except for loop diuretics, which have been proven to improve symptoms, reduce hospital stays, and increase survival rates in clinical trials. The choice of initial treatment is based on various factors, with all treatments eventually increased to the maximum tolerated or targeted dose.
4	Recommendation on the role of ARNI in HFrEF
	The guidelines recommend a combination of four medications for treating heart failure with reduced ejection fraction (HFrEF): ARNIs, mineralocorticoid receptor antagonists, beta-blockers, and sodium glucose cotransporter-2 inhibitors. The ACCF/AHA/HFSA guidelines give ARNI a Class 1A recommendation and the ESC guidelines give it a 1B recommendation. The PARADIGM HF trial demonstrated that sacubitril/valsartan had a lower rate of cardiovascular death hospitalization compared to enalapril, with better improvement in quality of life.
5	Recommendation on the role of ARNI in HFpEF
	The ACC guidelines have given a Class IIb recommendation for using ARNI in HFpEF. In the PARAGON-HF trial done in patients with EF of 45% or higher, the main outcome showed a non-significant reduction in cardiovascular deaths or heart failure hospitalizations in the sacubitril-valsartan group. Secondary outcomes confirmed a significant improvement in NYHA class and renal function, with more benefits seen in female patients and patients with EF between 45 to 57%, highlighting need for personalized therapy with ARNI in HFpEF.
6	Recommendation on continuing GDMT in HFimpEF
	Continue current GDMT in HFrEF patients with recovered LVEF unless there is a clear reversible cause, as discontinuing it leads to high rates of HF events (per TRED-HF study).
7	Recommendations on the role of ARNI in cardiac reverse remodeling
	Studies have shown that ARNIs can improve LV and diastolic function, quality of life, and reduce risk of ventricular arrhythmias, with positive results seen in trials such as PROVE-HF and EVALUATE-HF.
8	Recommendations on dose of ARNI
	The suggested initial dose of sacubitril/valsartan is 50 mg, to be taken orally twice daily. After a period of 2–4 weeks, the dosage can be increased to 100 mg and further escalated to 200 mg, based on the individual's tolerance. However, certain circumstances may require a reduction in the starting dose. These include patients who are not currently receiving an ACEi or ARB, individuals with severe renal impairment, individuals with blood pressure below 90/60, or patients with moderate hepatic impairment.
9	Recommendation on ARNI dose titration
	The initiation and dose increase of sacubitril/valsartan over 3 (for 100 mg bd starting dose) or 6 weeks (for 50 mg BD starting dose) has a tolerable profile and a more gradual increase maximized the target dose attainment in low-dose ACEI/ARB patients (TITRATION trial).
10	Recommendation on in-hospital initiation of ARNI
	The TRANSITION trial found initiation of sacubitril/valsartan to be feasible in patients with HFrEF who had stabilized after an acute heart failure event. The PIONEER-HF trial showed that sacubitril–valsartan was more effective than enalapril in reducing NT-proBNP levels in patients with HFrEF hospitalized for acute decompensation.
11	Recommendation on initiation of an ARNI de novo
	Starting directly on ARNI is safe and effective with improved cardiac function and tolerability and is recommended with monitoring and assessment considering the risk of angioedema or hypotension.
12	Recommendation of using ARNI with SGLT2 inhibitor
	ARNI may be combined with SGLT2i for the treatment of heart failure. Whenever diuretics are used, the dosage needs to be adjusted.
13	Recommendation on ARNI dose modification for hepatic dysfunction patients
	In HF patients with moderate hepatic impairment (Child–Pugh B), the loading dose of ARNI should be halved and the subsequent doses should be gradually increased to reach the maximum tolerated dose. No dose adjustment is needed in mild hepatic impairment (Child–Pugh A). ARNI should not be prescribed in patients with severe hepatic impairment.
14	Recommendation on ARNI in patients with CKD
	ARNI can be prescribed to non-dialysis patients with CKD and heart failure. Use of ARNI in such patients reduces cardiovascular risk and improves eGFR compared to ACEI/ARBs.
15	Recommendation on the dose titration of ARNI in renal impairment
	ARNI dose adjustment is not required in HF patients with mild to moderate renal impairment. Depending on the patient's blood pressure, a loading dose of 25–50 mg BID is advised in severe renal impairment. The dose of ARNI should be gradually increased every 2–4 weeks to reach the maintenance dose of 200 mg BID (maximum tolerated dose).
16	Recommendations on management of hypovolemia and hypotension in patients initiated on ARNI
	If low blood pressure or symptoms of hypotension are present, adjust diuretic and anti-hypertensive medication, address other causes, and rehydrate. Correct hypovolemia before starting ARNI or use low-dose ARNI to reduce the risk of hypotension. If the patient is still hypotensive, reduce the dose or temporarily discontinue ARNI; permanent discontinuation is usually not required.
17	Recommendation on management of hyperkalemia on initiating ARNI
	ARNI therapy may cause elevated potassium levels. Studies show slightly lower hyperkalemia incidence with ARNI compared to enalapril. If hyperkalemia occurs, address risk factors, discontinue potassium supplements and MRA, and use potassium-lowering drugs. ARNI may require temporary adjustment or discontinuation with close potassium monitoring. ARNI can be gradually resumed when potassium levels normalize.
18	Recommendation on management of patients with rapid decline in renal function on starting ARNI
	Patients with rapid decline in renal function from ARNI therapy have no specific treatment data, but RAAS inhibitor treatment methods can be used. Determine the cause of the decline, and if creatinine increases less than 30% from baseline, ARNI can continue. Adjust or discontinue ARNI and investigate underlying causes if creatinine exceeds baseline by 30%. Discontinue ARNI if creatinine exceeds baseline by 50%. Address other potential causes before considering ARNI adjustment or discontinuation.
19	Recommendations of ARNI in patients on maintenance dialysis
	ARNI is advised for heart failure patients receiving maintenance dialysis in order to enhance myocardial remodeling, safeguard remaining renal function, manage heart failure symptoms, and lower the risk of CV events.
20	Recommendations on improving medication adherence
	Dedicated heart failure clinics with regular follow-up with a heart failure nurse can help improve medication adherence. The use of a pre-discharge medication checklist is another helpful tool for improving GDMT implementation.