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Sacubitril-valsartan should not be given concomitantly ith ACE in ibitors due to risk for ngioedema, and ACE inhibitor treatment should be stopped for 36 h before starting treatment with ARNI. For patients with eGFR < 30 mL/min/1.73 m 2 or moderate hepatic impairment, the starting dosage of ARNI is 24/26 mg twice daily and ARNI is n t recommended for patients with sever hepatic impairment [ 38 ]. With the results of the PARADIGM trial, several new rec- ommendations have been added to the 2017 Focused Update HF Guidelines. First, for patients who are not treated with ACE inhibitors or angiotensin receptor blockers, the initial strategy of RAS inhibition can include either an ACE inhibitor or ARB or ARNI. The guidelines specify that the clinical strategy of inhibition of the RAS wi h ACE inhibitors (level of evidence: A), or ARBs (level of evidence: A), or ARNI (level of evidence: B – R) in conjunction with evidence-based beta-blockers and aldosterone antagonists in selected patients is recommended fo patients with chronic HFrEF to r duce morbidity and mortality [ 1 •• ]. In the 2017 Focused Update of HF Guidelines, in patients with chronic symptomatic HFrEF NYHA class II or III who tolerate an ACE inhibitor or ARB, replacement by an ARNI is recommended to further reduce morbidity and mortality [ 1 •• , 36 •• ]. In those patients who are being considered to be switched to ARNI from ACE inhibitors, it is very important to note that ARNI should not be administer d concomitant y with ACE inhibitors or within 36 h of the last dose of an ACE inhibitor due to angioedema risk [ 1 •• , 35 ]. Similarly, ARNI should not be administered to patients with a history of angio- edema [ 1 •• ]. In the studies with combine neprilysin a ACE inhibition, blacks and smokers were particularly at risk for angioedema [ 35 ]. It is helpful for patients receiving ARNI to be educated about recognition of the symptoms of angioede- ma and to ale t health care providers against concomitant pre- scription of ACE inhibitors with ARNI. In a phase II trial in patients with heart failure with pre- served ejection fraction, LCZ696 reduced NT-proBNP to a greater extent than did val artan at 12 weeks and was well tolerated [ 39 ]. The efficacy and safety of ARNI in acute de- compensated HF, in advanced HF patients with NYHA class IV symptoms, or in patients with HF-PEF is unclear at this time and is being tested in large-scale trials. Ivabradine Ivabradine is a specific and selective inhibitor of the If ion channel. If ion channel (the fu ny current) is highly expressed in spontaneously active cardiac regions, such as the sinoatrial node, the AV node, and the Purkinje fibers. The funny current is a mixed Na/K current that activates upon hyperpolarization at voltages in the diastolic range, and controls the rate of spontaneous activity of sinoatrial myocytes, hence the cardiac rate [ 40 ]. In the Systolic HF treatment with the If inhibitor Ivabradine Trial (SHIFT), among HFrEF with normal sinus rhythm and baseline heart rate ≥ 70 bpm despite treatment with beta-blockers, ivabradine treatment was associated with reduction in combined end point of cardiovascular death or HF hospitalization when compared against placebo [ 41 •• ]. Interestingly, though the trial inte ded to recruit patients on target or maximally tolerat d doses of β -blockers, 26% of patients were on full-dose β -blockers. The treatment effect reflected a reduction only in the risk of hospitalization for worsening HF; there was no benefit observed for the mortality compone t of the primary end point [ 41 •• ]. Patients enrolled included a small number with paroxysmal atrial fibrillation (< 40% of the time) but otherwise in sinus rhythm and a small number experiencing ventricular pacing but with a predomi- nant sinus rhythm [ 41 •• ]. Ivabradine patie ts had higher rates of symptomatic bradycardia, atrial fibrillation, and visual side effects (phosphenes) compared to placebo [ 41 •• ]. According to the FDA drug label, ivabradine is approved to reduce hospi- talization risk for worsening HF in pati nts with stable, symp- tomatic chronic HF with LVEF ≤ 35% in sinus rhythm with resting HR of ≥ 70 bpm or higher and on maximally tolerated doses of beta-blockers and is contraindicated for patients with acute decompensated HF, BP < 90/50 mmHg, patients with sick sinus syndrome, sinoatrial, or third-degree AV block [ 42 ]. In the 2017 Focused Update of HF Guidelines, iv bradine is identified as a treatment that can be beneficial to reduce HF hospitalization for patients with symptomatic (NYHA class II and III) stable chronic HFrEF (LVEF ≤ 35%) who are receiv- ing guideline-directed medical treatment, including a beta- blocker at maximum tolerated dose, and who are in sinus rhythm with a heart rate of ≥ 70 bpm at rest (class IIa recom- mendation, with level of evidence: B – R). It should be noted that the recommendation does not entail a statement regard ng mortality benefit. Contrary to the ESC Guidelines [ 43 ], in the 2017 AHA/ACC Focused Update of HF Guidelines, there is no recommendation for ivabradine in beta-blocker intolerant patients [ 1 •• ]. SHIFT trial w s not designed to exa in the efficacy of ivabr dine in patients intolerant to bet -blockers. Efficacy and benefit of ivabradine in beta-blocker intolerant patients need to be tested in future trials. The current treatment strategies for management of patients with HF and re uced EF are summarized in Figs. 1 and 2 . Update on the Treatment of HFpEF Unfortunately there are no treatment strategies with proven benefit to reduce mortality in patients with HF with preserved EF. Current treatment strategies target treatment of the underly- ing etiology for HF-pEF and comorbidities. Thus, most of the recommendations that were present in 2013 AHA/ACC HF 39 Page 4 of 9 Curr Cardiol Rep (2018) 20: 39 the inp tient setting prior to discharge and for cont nued mon- itoring during he th rd phase o outpatient follow up. Natriuretic p pt d measureme Comparing the serum lev l f NT-proBNP on admission and prior discharge can ensur the correct therapeutic trajectory [ 25 ]. NT-proBNP is cleaved from BNP, as more stability in vivo, and has be n shown to have higher sensitivi y an pecificity compared to circulating BNP levels [ 26 ]. Pa i nts with persisten ly elevated NT- proBNP prio to discharge have been found to have signifi- cantly igher risk for rehospitalization o death [ 27 ]. The util- ity of monitoring serial NT-proBNP levels in th inpatient setting s challenged by a delay in serum l vel chang s com- pared to intravascul r conge tion progression. Howev r, it h s been sh wn that a reduction in NT-proBNP levels by at least 30% from admission is associat d with an improveme t in pos -discharge outcomes [ 28 ]. Noni vasive hemodynamic monitoring can be used throughout th three phases f hosp talization for HF. In the emergen y department, utilization of ultrasound technology i becom ng mor convenient wi h the dvent of hand-held d - vices. Evaluation of inferior vena cava (IVC) compressibility or distension can easily be performed to distinguish between sys- temic congestion and flu d redistribution [ 29 ]. Goonewardena et al. det rmined t at bedside ultrasound of IVC, even with a hand-held d vice, identifi patients with ADHF who would go on to be readmitted for HF exacerbations based on ple horic IVCs with lower collapsibility i dexes [ 30 ]. Newer imaging modalities, such as bioelectri al impedanc vector analysis (BIVA), are being tested as options for intra- vascula ass ssment. The use of transthoracic bioe ectrical im- pedance analysis as a marker of fluid accumulation is still gaining traction in the cli ical world but it has demonstra ed relia ility in measuring cardiac output nd index when com- pared to invasive methods [ 31 ]. Augment use of underused therapies known to decrease rehospitalizat ons Current guideline-directed medical herapy (GDMT) h been well outlined by institutions i cluding the American College of Cardiology (ACC), American Heart Association (AHA), and European Soc ety of Cardiology (ESC) [32]. Despi e the well-established body of evidence supporting these guidelines for HFrEF, there remain significant gaps in provision of rec- ommen ed therapies to patients who qualify for them. This B risk-treatment paradox ^ and B clinical inertia ^ may stem from focus o the potential short-t rm destabilization of clin cal st tus, rather than consideration of the potential long-term benefits of therapy. For example, robust evidence suggests h t worsening renal function in the setting of augmented deco - gestive therapy or initiation of renin – angiotensin – aldosterone system (RAAS) blockade does not negatively impact progno is, but rather represent a net benefit to the pati nt [ 33 – 36 ]. Nonetheless, se patients frequently have their ACE inh bi- tors and angiotensin receptor blockers (ARBs) st pped with- out reinitiation pr or to disch rge. Si ilarly, in African American patient with stabl h modynamics, less than 25% are discharged on hy ralazine and isosorbide dinitrate despite data proving morbidity and mortality benefits in this cohort [ 37 ]. Below (and summ r zed in Tabl 1 ) a e ex mples herapies in HFrEF pati nts that ne d to ighlighted f r initiation either prior to discharge or during outpati n fol ow-up in order to further minim ze the risk-treatment par- adox and promot cardiac dysfunc i n re rsibility. Digoxin has prov n hemodynamic be efits and h s be n associated with decreased readmission r es. As such, it is endorsed by guidelines to u appropriate p tients with persistent symptoms and rehospitalizations for HFrEF. However, in e last decade, ther h s be n a decr ase in prescri ion rate to only 20 – 40% from 80% at the peak of its clinical utility [ 38 ]. Data suggesting increased mortality wi h digoxin are niformly o servational and subject to confound ing. The DIG trial demonstrated that igoxin, when added to diure cs and ACEi in patients with chronic HF EF in sinus hythm, decreased hospitalizations without ffecting mort lity [ 39 ]. This neutral ffect on m r al ty n a large randomized trial is notabl amid persistent concerns over the safety of digoxi in routine clin al p actice. Moreover, the neutral mor- tality effect of digoxin in the DIG tri l was se n despite th trial protocol calling for aggressiv dosing of the agent to achieve serum digox n concentrations above current guide- li es [ 32 ]. Evidence suggests that dosing in line with ACC/ AHA guidelines further improves the risk-benefit ratio of di g xin therapy. Mi er locorticoid receptor antagonists Less t an 33% of eli- gible p tients admitted for HF are started on mineralocorticoid receptor antagonists (MRAs) before discharge [ 40 ] despit data showing that MRAs significantly reduce arly hospital - zation rate [ 41 ]. In addition to blocki g aldosterone ’ s effect on the RAAS, MRAs have been able to prevent aldosterone ’ s promoti n of car omyocy e fibrosis, oxidativ injury, and cardiac remod ling [ 42 ]. At h gher doses, MRAs can also rovide atriuretic b n fits and has been used in cirrhotic pa- tients for this eff c for years [ 43 ]. Importantly, spironol ctone is one of the only edic tion to hav a possible role in min- imizing the readmission risk in HFpEF patients in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial [ 44 ]. Torsemide The t e most commonly used loop d uretic for- mularies are fur semide, bumetan de, and tors mide. Furosemide historically has been the most frequently used diur c initially due to cost and early marketing (furosemid Heart Fail Rev (2018) 23:597 – 607 601