Cardiology Internal Medicine

Heart Failure with Preserved Ejection Fraction (HFpEF)

Heart Failure with Preserved Ejection Fraction

Introduction – Heart Failure with Preserved Ejection Fraction

Heart failure is a clinical syndrome of heterogeneous nature with a variety of etiologies and varying symptoms. The type of heart failure that is most commonly known and documented is heart failure with reduced pumping capacity (ejection fraction = EF, <40%), called HFrEF (Heart Failure with reduced Ejection Fraction). It is also in this state that all evidence-based treatments are available.

However, it has long been known that a relatively large proportion (30-40%) of all chronic heart failure patients have not reduced EF, but EF in the normal range, >40-50%. This condition is called Heart failure with preserved Ejection Fraction (HFpEF), where EF >= 50%. HFpEF differs in several aspects compared to HFrEF, but is similar in other respects. There is no sharp border between the two types of heart failure. Patients may also diagnostically shift between HFpEF and HFrEF when EF is improved or worsened.

Recently, an intermediate category, HFmrEF (mid-range) (EF 40-49%) has been proposed. There is substantial evidence that HFmrEF is more similar to HFpEF compared to HFrEF. Reliable data on HFpEF are missing from larger registries because the diagnosis requires the evaluation of left ventricular function by the determination of EF. It is believed that this part of the heart failure population will increase in the future as the population grows older.


Etiology – Heart Failure with Preserved Ejection Fraction

The underlying causes of HFpEF may be the same as those of HFrEF, but the frequency of conditions within the groups varies. In HFpEF, the clinical picture is less dominated by ischemic heart disease and more by hypertension, atrial fibrillation and obesity. In addition, the patients are also older and there are more women compared to the HFrEF population. By definition, patients with more isolated right-sided heart failure also fall into this group when the left ventricle is not affected, such as in:

  • Right-sided valvulopathies
  • Pulmonary hypertension
  • Right-sided myocardial infarction

In HFpEF, the stiffness of the myocardium is considered to be of great importance, causing diastolic dysfunction, which was previously referred to as the condition of diastolic heart failure. It is now evident that both diastolic and systolic function is impaired in both types of heart failure, so the former term is not considered relevant. EF used to separate the groups is an unreliable measure. More refined diagnostics with, for example, tissue Doppler and so-called strain rate can usually detect disorders of systolic function even in HFpEF.

Increased stiffness in the left ventricle results from hypertrophy and scarring (fibrosis), and often these two factors are intertwined. Conditions with a high degree of cardiac hypertrophy and fibrosis are:

  • Hypertrophic cardiomyopathy
  • Hypertension
  • Aortic stenosis
  • Previously resolved inflammation that healed with residual fibrosis (myocarditis)

In addition, there are various metabolic storage diseases, especially amyloidosis, which give a clinical picture similar to HFpEF. One mechanism that has been discussed and which could be a cause of HFpEF is disturbed coronary circulation, especially microvascular dysfunction. However, this connection has not been investigated fully.


Symptoms – Heart Failure with Preserved Ejection Fraction

Symptoms and the overall clinical picture is similar to HFrEF and there is no way to differentiate the two forms solely by means of clinical judgment. Dyspnea and edema are classic symptoms. 

Differential diagnoses

  • Cardiac ischemia (angina pectoris, myocardial infarction) without heart failure
  • Pulmonary diseases, COPD, asthma
  • Pneumonia
  • Pulmonary embolism
  • Renal or liver failure with edema
  • Peripheral causes of edema
  • Anemia or bleeding

Diagnostics

Medical history

As in Heart Failure with Reduced Ejection Fraction (HFrEF).


Medical Examination

As in HFrEF (chronic heart failure)


Lab tests

As in HFrEF (chronic heart failure). See also the Diagnostic criteria.


Diagnostic Imaging – Heart Failure with Preserved Ejection Fraction

Diagnostic imaging is the same as in HFrEF (chronic heart failure). To distinguish between the two types of heart failure, it is necessary to make a determination of EF, usually with echocardiography (cardiac ultrasound). This method can sometimes be uncertain as you do not always get an exact value of EF. Magnetic resonance (MRI) examination provides a more accurate diagnosis of EF.

Since HFpEF can be difficult to distinguish from other conditions that cause the same symptoms, and cardiac examinations sometimes show marginal abnormalities at rest, testing during stress provocation can be of value. In cardiac catheterization, one gets an accurate assessment of the heart’s filling pressure, which is usually elevated in heart failure of various types. In addition, physical exertion can be used to cause a provocation that reveals an abnormal increase in filling pressures. Stress testing can also be performed during echocardiography but is not yet routinely used for this diagnosis. Filling pressures cannot be accurately measured with echocardiography, but diastolic function can be evaluated.

Diagnostic criteria – Heart Failure with Preserved Ejection Fraction

A diagnostic algorithm has been proposed by the European Society of Cardiology (ESC). This applies to both types of heart failure. To diagnose HFpEF (or HFmrEF), the following applies:

  • In order to make the diagnosis, symptoms consistent with heart failure, plus clinical signs are required (the latter may sometimes be missing at an early stage of the condition)
     
  • In addition, an elevation in natriuretic peptides (BNP >35 ng/L or NT-proBNP >125 ng / L *) is required.
     
  • In addition, at least one of the following signs of impaired cardiac function:
    (1) Left ventricular hypertrophy or enlarged left atrium.
    (2) Signs of disturbed diastolic function on echocardiography. **

* These natriuretic peptide values ​​are low and used to rule out heart failure. Diagnostics require higher values, which vary depending on the laboratory measurement method and especially the age of the patient. Results ​​of NT-proBNP exceeding 500-1000 ng/L are usually present in recently discovered heart failure.

** Signs of diastolic dysfunction include, among other things, decreased diastolic tissue velocity e’ <9 cm/s in the septum or lateral wall; E/e’ >13; decreased longitudinal strain; assessment of flow in pulmonary veins and through the mitral valve; signs of elevated right-sided pressures estimated by measurements of the gradient across the tricuspid valve.


Treatment – Heart Failure with Preserved Ejection Fraction

Chronic

There is no evidence-based treatment for HFpEF. In a recent large meta-analysis of beta-blockers in heart failure, it was found that the positive effect of beta-blockers in HFrEF and sinus rhythm was similar in HFmrEF, but was not seen in HFpEF. In the CHARM-PRESERVED trial, Candesartan was associated with a trend towards fewer hospital admissions but with no effect on mortality. Spironolactone has been studied in the TOPCAT trial, which was negative in its main part, but showed a subgroup that had positive results in patients not treated in Russia.

In Sweden, a large registry-based randomized study covering this topic has recently been started (SPIRRIT). The new drug sacubitril/valsartan (Entresto) used in HFrEF is now being tested in HFpEF (PARAGON-HF) with the hope of showing beneficial effects here as well. Several other studies attempting to alter mechanisms such as microvascular dysfunction and inflammation are also ongoing.

Available treatment is mainly focused on symptom relief. Often, patients have fluid retention and need to have diuretics at appropriate doses. It is also of value to check for comorbidities, for example:

  • COPD / asthma
  • Diabetes
  • Hypertension
  • Atrial fibrillation
  • Anemia
  • Kidney failure

There is also a high degree of co-morbidity in HFrEF but the profile is slightly different. In the treatment of hypertension, angiotensin receptor blockers (ARBs) and mineralocorticoid receptor antagonists (MRAs) should be used as first hand agents.

Other symptom-relieving treatments such as intravenous iron and physiotherapy are reasonable to use, although these interventions do not have substantial evidence in HFpEF either. Cardiac resynchronization therapy (CRT) and ICD (implantable cardioverter defibrillator) implantation, which is indicated in HFrEF, does not have significant positive evidence in HFpEF.


Follow-up – Heart Failure with Preserved Ejection Fraction

The need for long-term and lifelong care is the same as in HFrEF. Monitoring the degree of fluid retention and administering an adequate dose of diuretics is of great value. It should also be kept in mind that some patients may have impaired cardiac function and then fall into the HFrEF group, resulting in a more serious condition, but also a larger arsenal of treatment options.


Prognosis

The prognosis in HFpEF is slightly better than in HFrEF, but still with high mortality and high morbidity (risk of need for hospital care). In a large meta-analysis (MAGGIC), patients with HFpEF had lower mortality rates than those with HFrEF (adjusted for age, gender, etiology, hypertension, diabetes and atrial fibrillation): hazard ratio 0.68 (95% CI: 0.64-0.71).


Further Reading