Heart failure guidelines: What you need to know about the 2017 focused update

Cleveland Clinic Journal of Medicine. 2019 February;86(2):123-139 | 10.3949/ccjm.86a.18022
February 1, 2019|Cleveland Clinic Journal of Medicine
Lee Rodney Haselhuhn, MD;Daniel J. Brotman, MD;Ilan Shor Wittstein, MD
Author and Disclosure Information

Lee Rodney Haselhuhn, MD
Department of Medicine, Johns Hopkins University, Baltimore, MD

Daniel J. Brotman, MD
Department of Medicine, Johns Hopkins University, Baltimore, MD

Ilan Shor Wittstein, MD
Departments of Medicine and Cardiology, Johns Hopkins University, Baltimore, MD

Address: Lee Rodney Haselhuhn, MD, Division of General Internal Medicine, Johns Hopkins Hospitalist Program, Johns Hopkins Hospital, 600 N. Wolfe St., Meyer 8-134M, Baltimore, MD 21287; lhaselh1@jhmi.edu

Dr. Brotman has disclosed consulting for Portola Pharmaceuticals.

Release date: February 1, 2019
Expiration date: January 31, 2020
Estimated time of completion: 1 hour

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ABSTRACT

The 2017 focused update of the 2013 ACC/AHA guideline on heart failure contains new and important recommendations on prevention, novel biomarker uses, heart failure with preserved ejection fraction (HFpEF), and comorbidities such as hypertension, iron deficiency, and sleep-disordered breathing. Potential implications for management of acute decompensated heart failure will also be explored.

KEY POINTS

  • Despite advances in treatment, heart failure remains highly morbid, common, and costly. Prevention is key.
  • Strategies to prevent progression to clinical heart failure in high-risk patients include new blood pressure targets (< 130/80 mm Hg) and B-type natriuretic peptide screening to prompt referral to a cardiovascular specialist.
  • An aldosterone receptor antagonist might be considered to decrease hospitalizations in appropriately selected stage C HFpEF patients. Routine use of nitrates or phosphodiesterase-5 inhibitors in such patients is not recommended.
  • Outpatient intravenous iron infusions are reasonable in persistently symptomatic New York Heart Association stage II to III heart failure with reduced ejection fraction (HFrEF) to improve functional capacity and quality of life.
  • The new systolic blood pressure target is less than 130 mm Hg for stage A heart failure, stage C HFrEF, and stage C HFpEF.

SHOULD ALDOSTERONE ANTAGONISTS BE USED IN ACUTE HFpEF?

Given the encouraging results in chronic HFpEF from post hoc analyses of TOPCAT, are there any additional recent data suggesting a role for aldosterone antagonists such as spironolactone in acute HFpEF?

The ATHENA-HF trial

The Aldosterone Targeted Neurohormonal Combined With Natriuresis Therapy in Heart Failure (ATHENA-HF) trial63 compared treatment with high-dose spironolactone (100 mg) for 96 hours vs usual care in 360 patients with ADHF. The patient population included those with HFrEF and HFpEF, and usual care included low-dose spironolactone (12.5–25 mg) in roughly 15% of patients. High-dose mineralocorticoid receptor antagonists have been shown to overcome diuretic resistance, improve pulmonary vascular congestion, and partially combat the adverse neurohormonal activation seen in ADHF.

Unfortunately, the trial was completely neutral in regard to the primary end point of reduction in natriuretic peptide levels as well as to the secondary end points of 30-day mortality rate, heart failure readmission, clinical congestion scores, urine output, and change in weight. No suggestion of additional benefit was seen in subgroup analysis of patients with acute HFpEF (ejection fraction > 45%), which yielded similar results.63

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Given these lackluster findings, routine use of high-dose spironolactone in ADHF is not recommended.64 However, the treatment was well tolerated, without significant adverse effects of hyperkalemia or kidney injury, leaving the door open as to whether it may have utility in selected patients with diuretic resistance.

Should ARNIs and ivabradine be started during ADHF admissions?

The first half of the focused update3 of the 2013 guidelines,2 reviewed by Okwuosa et al,7 provided recommendations for the use of sacubitril-valsartan, an angiotensin-neprilysin inhibitor (ARNI), and ivabradine, a selective sinoatrial node If channel inhibitor, in chronic HFrEF.

Sacubitril-valsartan was given a class I recommendation for use in patients with NYHA class II or III chronic HFrEF who tolerate an ACE inhibitor or an ARB. This recommendation was given largely based on the benefits in mortality and heart failure hospitalizations seen in PARADIGM-HF (the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure)65 compared with enalapril (HR 0.80, 95% CI 0.73–0.87, P < .001).

There is currently no recommendation on initiation or use of ARNIs during admissions for ADHF, but a recent trial may lend some insight.66

THE PIONEER-HF trial

The Comparison of Sacubitril/Valsartan vs Enalapril on Effect on NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode (PIONEER-HF) trial66 randomized patients admitted for acute HFrEF, once stabilized, to sacubitril-valsartan or enalapril. Encouragingly, the percentage change of natriuretic peptide levels from the time of inpatient initiation to 4 and 8 weeks thereafter, the primary efficacy end point, was 46.7% with sacubitril-valsartan versus 25.3% with enalapril alone (ratio of change 0.71, 95% CI 0.63–0.81, P < .001). Although not powered for such, a prespecified analysis of a composite of clinical outcomes was also favorable for sacubitril-valsartan, largely driven by a 44% decreased rate of rehospitalization. More definitive, and quite reassuring, was that no significant difference was seen in the key safety outcomes of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema. These results were also applicable to the one-third of study participants who had no former diagnosis of heart failure, the one-third identifying as African American, and the one-third who had not been taking an ACE inhibitor or ARB. These results, taken together with the notion that at study completion the patients become similar to those included in PARADIGM-HF, have led some to assert that PIONEER-HF has the potential to change clinical practice.

Ivabradine was given a class IIa recommendation for use in patients with NYHA class II or III chronic HFrEF with a resting heart rate of at least 70 bpm, in sinus rhythm, despite being on optimal medical therapy including a beta-blocker at a maximum tolerated dose.

This recommendation was largely based on SHIFT (Systolic Heart Failure Treatment With the If Inhibitor Ivabradine Trial), which randomized patients to ivabradine or placebo to evaluate the effects of isolated lowering of the heart rate on the composite primary outcome of cardiovascular death or hospitalization. A significant reduction was seen in the ivabradine arm (HR 0.82, 95% CI 0.75–0.90, P < .0001), mainly driven by decreased hospitalizations.67

Subsequently, a small unblinded single-center study was undertaken to evaluate the efficacy and safety of initiating ivabradine during admissions for ADHF.68

THE ETHIC-AHF trial

The Effect of Early Treatment With Ivabradine Combined With Beta-Blockers vs Beta-Blockers Alone in Patients Hospitalized With Heart Failure and Reduced Left Ventricular Ejection Fraction (ETHIC-AHF) trial68 sought to determine the safety and effectiveness of early coadministration of ivabradine with beta-blockers in patients with acute HFrEF.

This single-center, unblinded study randomized 71 patients to ivabradine and beta-blockade or beta-blockade alone upon clinical stabilization (24–48 hours) after admission for acute decompensated HFrEF.

The primary end point was heart rate at 28 days, with the ivabradine group showing a statistically significant decrease (64 vs 70 bpm, P = .01), which persisted at 4 months. There was no significant difference in the secondary end points of adverse drug effects or the composite of clinical event outcomes (all-cause mortality, admission for heart failure or cardiovascular cause), but a number of surrogate end points including left ventricular ejection fraction, BNP level, and NYHA functional class at 4 months showed mild improvement.

Although this study provided evidence that the coadministration of ivabradine and a beta-blocker is safe and was positive in regard to clinical outcomes, the significant limitations due to its size and study design (single-center, unblinded, 4-month follow-up) simply serve to support the pursuit of larger studies with more stringent design and longer follow-up in order to determine the clinical efficacy.