Heart failure is a complex clinical syndrome that results from any functional or structural heart disorder, impairing ventricular filling or ejection of blood to the systemic circulation to meet the systemic needs. Heart failure can be caused by diseases of the endocardium, myocardium, pericardium, heart valves, vessels or metabolic disorders. Most patients with Heart failure have symptoms due to impaired left ventricular myocardial function. Patients usually present with symptoms of dyspnea, decreased exercise tolerance and fluid retention, characterized by pulmonary and peripheral edema.

Heart failure due to left ventricular dysfunction is categorized according to left ventricular ejection fraction (LVEF) into heart failure with reduced ejection fraction (usually considered LVEF 40% or less), known as HFrEF and heart failure with preserved ejection fraction; known as HFpEF. The definition of HFrEF has varied among different studies and guidelines with different left ventricular ejection fraction (LVEF) cut-offs of ≤35%, <40%, and ≤40%. Randomized controlled trials in patients with HF have mainly enrolled patients with HFrEF with an EF ≤35% or ≤40%, and it is only in these patients that efficacious therapies have been demonstrated to date. According to the most recent ACC/AHA guidelines on heart failure, HFrEF is defined as the clinical diagnosis of HF with EF ≤40%. In routine clinical practice, many clinicians would consider EF <45% as significant systolic dysfunction and would consider it as HFrEF.

Heart failure with preserved ejection fraction (HFpEF) on the other hand has also been variably classified as EF >40%, >45%, >50%, and/or ≥55%. The term HFpEF has been used since some of these patients do not have entirely normal EF but also do not have a major reduction in the systolic function. Patients with an EF between the range of 40% to 50% have been considered to represent an intermediate group of patients due to a variable cut off used for systolic dysfunction by the different studies. These patients should be routinely treated for underlying risk factors and comorbidities and with optimal guideline-directed therapy, similar to that of HFrEF.

When heart failure develops, compensatory mechanisms attempt to increase the cardiac filling pressure, muscle mass and heart rate. However, in many cases, there is usually a progressive decline in heart function.

Heart failure is caused by several disorders, including diseases affecting the pericardium, myocardium, endocardium, cardiac valves, vasculature, or metabolism.

The most common causes of systolic dysfunction (HFrEF) are idiopathic dilated cardiomyopathy (DCM), coronary heart disease (ischemic), hypertension, and valvular disease.

Hypertension, obesity, coronary artery disease, diabetes mellitus, atrial fibrillation, and hyperlipidemia are highly prevalent in HFpEF patients. Hypertension by far is the most important cause of HFpEF. In addition, conditions like hypertrophic obstructive cardiomyopathy, and restrictive cardiomyopathy are associated with significant diastolic dysfunction, leading to HFpEF.  

Causes of high-output failure include:

• Anemia
• Hyperthyroidism
• AV fistulas
• Beri-beri
• Multiple myeloma
• Pregnancy
• Paget disease of bone
• Carcinoid syndrome
• Polycythemia vera

Very common causes of decompensation in a stable patient with HF include:

• Excess intake of sodium in the diet
• Inappropriate reduction in medications
• Lack of physical activity
• Lack of medication compliance
• Prolonged physical activity
• Emotional crisis
• Sudden changes in weather
• Excess intake of water

Approximately 5.1 million people in the United States have clinically manifest heart failure, and the prevalence continues to increase. Heart failure incidence has remained stable over the past decades, with more than 650,000 new cases of heart failure cases diagnosed annually, especially for individuals greater than 65 years of age. Because prevalence is greater in this age group, heart failure prevalence is expected to worsen in the near future.Epidemiological differences have been noted. Black men have the highest incidence rate (1000 person-years) for heart failure and the greatest five-year mortality rate when compared to whites. White women represent the lowest incidence. Heart failure in non-Hispanic black males and females has a prevalence of 4.5% and 3.8%, respectively, versus 2.7% and 1.8% in non-Hispanic white males and females, respectively. Although survival has improved, the absolute mortality rates for patients with heart failure remain approximately 50% within five years of diagnosis. The survival rate is inverse proportional to the staging severity of heart failure. The 5-year survival for stage A, B, C, and D heart failure was found to be 97%, 96%, 75%, and 20%, respectively in a study.

By 2013, heart failure costs in the United States exceeded $30 billion.

Gender differences in heart failure:

1. Between ages 65-85, heart failure incidence doubles in men but at the same time it triples in women
2. Women are likely to have preserved systolic function compared to men
3. Women, in general, develop heart failure later in life compared to men
4. While the symptoms of heart failure are similar in both genders, they are often severe in females
5. Women with heart failure tend to have longer survival times compared to men

Heart failure in Developing nations

• The majority of cases of heart failure are from non-ischemic causes
• Patients generally tend to be young
• Because of limitations in resources, the outcomes are worse
• Isolated right heart failure is more common, and may be linked to lung disease, pollution, pericardial disease, and tuberculosis.

The adaptive mechanisms that may be adequate to maintain the overall contractile performance of the heart at relatively normal levels become maladaptive when trying to sustain adequate cardiac performance. The primary myocardial response to chronically increased wall stress is myocyte hypertrophy, death due to apoptosis, and regeneration. This process eventually leads to remodeling, usually the eccentric type, and reduced cardiac output, causing a cascade of the neurohumoral and vascular mechanism.

Decreased carotid baroreceptor stimulation and renal perfusion will activate the sympathetic nervous system and Renin-Angiotensin-Aldosterone system. 

Sympathetic nervous system activation will cause increased heart rate and inotropy, leading to myocardial toxicity. Renin-Angiotensin-Aldosterone system activation leads to vasoconstriction, increasing afterload (angiotensin II) and hemodynamic alterations, increasing preload (aldosterone).

Both BNP and ANP are peptides released from the atria and ventricles in reposne to heart chamber pressure/volume expansion. These peptides promote natriuresis and vasodilatation. In addition. BNP inhibits the reabsorption of sodium in the proximal convoluted tubule. It also suppresses renin and aldosterone release.

In patients with HFpEF there is impaired  relaxation and increasing ventricle stiffness, leading to dysfunction in diastolic filling of the left ventricle. Patients with concentrcleft ventricular hypertrophy have a shift of the diastolic pressure volume curve to the left, leading to elevation in diastolic pressures, which leads to increased energy expenditure and oxygen demand and myocardial ischemia.

All of these mechanisms will cause negative remodeling and worsen the left ventricular function, causing symptoms of heart failure.