Prof. Dr. Sundeep Mishra discusses the diagnosis and treatment modality of heart failure with preserved ejection fraction based on the ESC 2016 and American Society of Echocardiography and European Association of Cardiovascular Imaging guidelines in 2016.

Heart failure (HF) with preserved ejection fraction (HFpEF) contributes to nearly 50% of patients presenting with heart failure. Heart failure is a clinical diagnosis that is reached based on the patient’s symptoms and examination findings. However, it is difficult to distinguish between HFrEF and HFpEF on clinical grounds. Certain subtle clinical findings such as the absence of cardiomegaly or presence of S4 (and no S3) may suggest HFpEF.

The ESC 2016 guidelines suggest an algorithmic approach to diagnose heart failure.

1. This includes the use of natriuretic peptides (NP) levels and echocardiography.
2. The plasma concentration of NP is a good rule-out test for HF. Plasma concentration of brain natriuretic peptide (BNP) <35 pg/ml and NT-pro-BNP <125 pg/ml can help in excluding HF.
3. Echocardiography is required to confirm the diagnosis and suggest possible etiology and classify HF. Echocardiographically, diagnosis of HFpEF requires demonstration of normal systolic ejection fraction (EF) with significant diastolic dysfunction.

Regarding systolic function, different trials related to HFpEF have used variable cut-offs for EF. To avoid any ambiguity in definition of HFpEF, the ESC 2016 guidelines have used the term heart failure with mid-range ejection fraction (HFmrEF)for patients with EF between 40-49%. Patients with EF ≥ 50% are classified as HFpEF. However, for practical purposes, it is reasonable to manage patients with HFmrEF also as HFpEF. Assessment of diastolic dysfunction is an important aspect in the diagnosis of HFpEF.

The latest guidelines on the echocardiographic assessment of diastolic dysfunction were published by the American Society of Echocardiography and the European Association of Cardiovascular Imaging in 2016. The definitive diagnosis of diastolic dysfunction requires presence of at least three of four qualifying criteria which include:

• Mean E/e’ >14 (septal E/e’ >13 or lateral E/e’ >15)
• Lateral e’ velocity <10 cm/sec or medial e’ velocity <7 cm/sec
• Tricuspid regurgitation velocity >2.8 m/sec
• LA volume index >34 ml/m²

After the diagnosis has been established the diastolic dysfunction should be graded for I-III.

Thus, echocardiographic parameters can suggest elevated left atrial pressure or left ventricular (LV) filling pressure and help in guiding therapy especially regarding the use of diuretics.

Treatment of HFpEF

The general management of patients with HFrEF or HFpEF is similar. All patients should be educated regarding self-care. Guideline directed medical therapy (GDMT) for HFpEF is limited. Since, most hospitalizations in patients with HFpEF occur because of co-morbidities, it is important to identify and managing such co-morbidities; hypertension, diabetes mellitus, and CAD.

Lifestyle Modification

1. Restriction of dietary sodium can be considered in severely symptomatic patients while general advice to restrict sodium <3 g/day appears appropriate in most patients.
2. Patients should be screened for sleep-related breathing disorders and the same managed with positive pressure ventilation.
3. Exercise training should be prescribed for all symptomatic patients who can participate as it improves functional status. Specifically, cardiac rehabilitation improves outcomes and should be considered wherever feasible.
4. Patients should be encouraged to maintain optimal weight.
5. Pneumococcal vaccine and annual influenza vaccine should be prescribed to all patients with HF.

Pharmacotherapy

Options for GDMT of HFpEF are limited. Diuretics could be used for symptomatic patients to decrease pulmonary venous congestion and loop diuretics are the drugs of the first choice.

Mineralocorticoid receptors antagonists (MRAs) may be considered reasonable in patients with HFpEF for reducing HF hospitalizations. Eligible candidates for this include those with symptoms and an EF ≥ 45%, increased levels of NP, serum creatinine < 2.5 mg/dL and normal serum potassium levels. This recommendation is based on the TOPCAT trial which was a multicenter study designed to investigate the effects of spironolactone on outcomes in patients with HFpEF (EF ≥45%). It included over 3000 patients who were randomized to receive either spironolactone or placebo and followed-up over 3.3 years. The primary outcome was a composite of cardiovascular death, aborted cardiac arrest, or HF hospitalizations. There was 17% reduction in HF hospitalizations (P = 0.04) was observed. However, the incidence of hyperkalemia doubled (18.7% vs. 9.1%) and serum creatinine increased more frequently in patients receiving spironolactone.

Use of angiotensin receptor blockers (ARB) is a class IIB recommendation for patients with HFpEF. This comes from the evidence from the CHARM-Preserved Randomized Trial which studied the utility of the ARB candesartan in >3000 patients with HFpEF (LVEF >40 %). The primary outcome was cardiovascular death or hospitalization for CHF. After a median follow-up of 36.6 months, there was no difference in the primary outcome or cardiovascular deaths, but there was a significant reduction in hospitalization for CHF.

Atrial fibrillation (AF) is a common complication in patients with HFpEF. Patients often deteriorate at the onset of AF. Management should be based on standard guidelines, but in patients with refractory HF, rhythm control should be preferred. Catheter ablation has emerged as an effective and safe alternative to pharmacological rhythm control, especially in patients with paroxysmal AF or early AF. Most of the patients are candidates for anticoagulation (elderly, heart failure and often hypertension) and direct-acting oral anticoagulants remain the drugs of first choice.

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The writer, Dr. Sundeep Mishra is a Professor of Cardiology.