Heart Failure

Heart failure (HF) is a clinical manifestation induced by several cardiovascular pathologies.

It can be characterized by inefficiency of the heart to pump enough oxygenated blood to the body. HF is associated with an overall decrease in quality of life and high rates of admission to the hospital and mortality.

HF severity is categorized according to the New York Heart Association (NYHA) classification groups:

• NYHA Class I: No symptoms and no limitation in physical activity
• NYHA Class II: Mild symptoms, mild shortness of breath and/or angina, mild limitation to physical activity
• NYHA Class III: Marked limitation in physical activity caused by symptoms, decreased physical capacity, only comfortable at rest
• NYHA Class IV: Severe limitation to physical activity, experiences symptoms while at rest, mainly hospitalized patients

HF can be further divided into sub-categories based on the patient’s ejection fraction (EF).

Three sub-categories have been accepted to date: Heart Failure with Reduced Ejection Fraction (HFrEF), Heart Failure with Mid-Range Ejection Fraction (HFmrEF), and Heart Failure with Preserved Ejection Fraction (HFpEF).

HFrEF, and partially HFmrEF, have well-established treatment strategies which are effective in reducing morbidity and outcome. Conversely, specific biomarkers and treatments for HFpEF patients are urgently needed.

Common causes of HF regardless of subtype include coronary heart disease, previous myocardial infarction(s), high blood pressure, arrhythmias, and cardiomyopathy.

Cardiac fibrosis is a pathological process characterized by the accumulation of extracellular matrix proteins, such as collagens, within the cardiac muscle. It is a common feature of all types of heart failure and is associated with impaired cardiac function.

The degree of cardiac fibrosis in HFpEF is associated with the severity of diastolic dysfunction and is a predictor of adverse clinical outcomes. Therefore, understanding the balance of the formation and degradation of ECM proteins in HFpEF patients is of crucial importance.

HFpEF is a subtype of HF in which the patients have an EF above 50%, and it is projected to become the dominant type of HF in the coming years.

Clinical manifestations of HFpEF are similar to other types of HF. HFpEF is a complex pathology influenced by the severity of comorbidities such as diabetes, obesity, and hypertension.

HFpEF is greatly affected by cardiac fibrosis induced by extrinsic factors such as diabetes and hypertension. Cardiac fibrosis, in combination with other processes significantly contributes to HFpEF pathogenesis.

According to recent reports, 26 million people live with heart failure worldwide. In the United States, heart failure affects approximately 6.2 million adults and is the leading cause of hospitalization among people over the age of 65.

Similarly, in Europe, an estimated 15 million people are affected by heart failure, with heart failure being the leading cause of hospitalization in people over the age of 65 in the European Union.

In both US and Europe, approximately 50% of HF patients have heart failure with preserved ejection fraction (HFpEF).

Heart failure with preserved ejection fraction (HFpEF) is diagnosed through a thorough evaluation that involves a medical history, physical examination, and various tests, such as electrocardiogram, echocardiogram, and cardiopulmonary exercise testing.

EF and end-diastolic volume are assessed. In addition to these diagnostic tools, circulating biomarkers that indicate the presence and severity of heart failure may also be used.

Common biomarkers for HFpEF include brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP). In case of uncertainty and to establish etiology, the patient is referred to further testing such as echocardiographic testing (diastolic stress test), hemodynamic measurements, cardiac MRI, and genetic testing