AI Heart Failure

Etiology, Symptoms, and Pharmacotherapy for Heart Failure


Heart failure (HF) is a complex and debilitating condition characterized by the heart’s inability to pump blood to meet the body’s demands adequately. It is often accompanied by the elevation of pulmonary or systemic venous pressures, leading to organ congestion and dysfunction. Understanding the etiology, classification, symptoms, and pathophysiology of HF is essential for all healthcare professionals, including pharmacists. Pharmacotherapy for heart failure can enable early intervention and effective treatment strategies.  

Management strategies encompass a multifaceted approach that includes lifestyle modifications, non-pharmacologic interventions, and pharmacotherapy. Evidence-based pharmacotherapy is crucial in improving outcomes and quality of life for patients with HF. 

Recommended course: Heart Failure: Evidence Review and Management 

Etiology of heart failure 

Heart failure can arise from various underlying conditions that impair the heart’s ability to pump blood effectively. Several factors contribute to the development of heart failure: 

  • Coronary artery disease and heart attack: Narrowed arteries due to coronary artery disease restrict blood flow to the heart, leading to weakened heart muscles.  A heart attack can further damage the heart muscle, impairing its pumping function. 
  • High blood pressure (hypertension): Prolonged high blood pressure forces the heart to work harder, eventually weakening its muscles and compromising its ability to pump blood efficiently. 
  • Heart valve disease: Malfunctioning heart valves disrupt the normal flow of blood, causing the heart to overwork and eventually leading to heart failure. 
  • Myocarditis: Inflammation of the heart muscle, often caused by viral infections like COVID-19, can result in left-sided heart failure. 
  • Congenital heart defects: Structural abnormalities in the heart present at birth can lead to heart failure, as the heart struggles to pump blood effectively. 
  • Arrhythmias: Abnormal heart rhythms can disrupt the heart’s pumping function, contributing to heart failure.  
  • Other contributing factors: Certain diseases like diabetes, HIV infection, thyroid disorders, and obesity, as well as lifestyle factors such as alcohol consumption and smoking, increase the risk of heart failure. 

Classification of heart failure 

Heart failure can be classified based on the affected side of the heart and the heart’s pumping ability: 

  • Right-sided heart failure: This type affects the right ventricle, causing fluid buildup in the body’s extremities, such as the legs and abdomen. 
  • Left-sided heart failure: The left ventricle is primarily affected, leading to fluid accumulation in the lungs, which can cause symptoms like shortness of breath. 
  • Heart failure with reduced ejection fraction (HFrEF): In this condition, also known as systolic heart failure, the left ventricle fails to contract effectively. This reduces the amount of blood pumped out of the heart with each beat. 
  • Heart failure with preserved ejection fraction (HFpEF): In this type, the left ventricle has difficulty relaxing and filling with blood properly despite maintaining a normal ejection fraction. 

Symptoms and pathophysiology of heart failure 

Heart failure is a multifaceted syndrome characterized by complex interactions between structural, functional, and biochemical abnormalities within the cardiovascular system. Recognizing the symptoms of heart failure is crucial for early diagnosis and management: 

  • Shortness of breath, especially during physical activity or while lying down 
  • Fatigue and weakness 
  • Swelling in the legs, ankles, and feet 
  • Rapid or irregular heartbeat 
  • Persistent cough, sometimes with white or pink mucus 
  • Sudden weight gain due to fluid retention 
  • Nausea, lack of appetite, and difficulty concentrating 
  • Chest pain 

Heart failure with preserved ejection fraction (HFpEF) 

Heart failure with preserved ejection fraction (HFpEF), also called diastolic heart failure.  HFpEF is characterized by structural and cellular alterations that impair the left ventricle’s ability to relax properly. This results in impaired LV filling without a significant reduction in ejection fraction (≥ 50%). Chronic comorbidities such as arterial hypertension, type 2 diabetes mellitus, obesity, renal insufficiency, and pulmonary diseases are often associated with HFpEF.   

Heart failure with reduced ejection fraction (HFrEF) 

In contrast, HFrEF can arise from abnormalities in systolic function, diastolic function, or both. Systolic heart failure, also known as heart failure with reduced ejection fraction (HFrEF), is characterized by global left ventricular (LV) systolic dysfunction. This leads to decreased ejection fraction (≤ 40%) and increased diastolic volume and pressure.  Common causes of HFrEF include myocardial infarction, myocarditis, and dilated cardiomyopathy. 

Heart failure with mildly reduced ejection fraction (HFmrEF) 

Additionally, heart failure with mildly reduced ejection fraction (HFmrEF) refers to patients with an LV ejection fraction of 41 to 49%, whose condition may overlap with features of both HFrEF and HFpEF. 

LV and RV failure 

In LV failure, cardiac output decreases while pulmonary venous pressure increases, leading to pulmonary congestion and fluid extravasation into the interstitial space and alveoli, resulting in pulmonary edema. RV failure, on the other hand, is characterized by increased systemic venous pressure, leading to fluid retention and edema in dependent tissues such as the feet, ankles, and abdominal viscera.  RV failure commonly causes hepatic congestion and dysfunction, contributing to fluid accumulation and systemic symptoms. 

Age-related changes 

Aging is associated with structural and functional changes in the heart and cardiovascular system, including increased myocardial stiffness, impaired diastolic function, and decreased responsiveness to beta-adrenergic stimulation. These age-related changes lower the threshold for heart failure and increase susceptibility to cardiovascular stressors. Other pathophysiologies of heart failure include renal, hemodynamic, neurohumoral, and cardiac responses. 

Evidence-based pharmacotherapy for heart failure 

The updated guidelines from the American College of Cardiology, American Heart Association, and Heart Failure Society of America provide comprehensive frameworks for managing HF. These guidelines reflect significant advancements in our understanding of HF pathophysiology and treatment options. They also offer clinicians evidence-based strategies to optimize patient care.  

Pharmacotherapy for heart failure: HFrEF 

For patients with HFrEF, the cornerstone of pharmacotherapy for heart failure revolves around guideline-directed medical therapy (GDMT). This comprises several core medication classes. These include: 

  • Angiotensin-converting enzyme inhibitors (ACEIs) and Angiotensin Receptor Blockers (ARBs): ACEIs and ARBs are recommended as first-line agents for HFrEF.  They exert beneficial effects by antagonizing the renin-angiotensin-aldosterone system (RAAS). This leads to vasodilation and attenuating maladaptive cardiac remodeling. 
  • Beta blockers: Beta blockers are integral in managing HFrEF, offering benefits in reducing morbidity and mortality by antagonizing the harmful effects of catecholamines on the heart. 
  • Mineralocorticoid receptor antagonists (MRAs): MRAs such as spironolactone and eplerenone play a crucial role in HFrEF management by counteracting the harmful effects of aldosterone excess, including sodium and water retention and myocardial fibrosis. 
  • Sodium-glucose cotransporter-2 inhibitors (SGLT2Is): Recent guidelines have included SGLT2Is as a fundamental component of GDMT for HFrEF.  These agents have demonstrated remarkable efficacy in reducing cardiovascular events and mortality, independent of their glucose-lowering effects. 
  • Angiotensin receptor-neprilysin inhibitors (ARNIs): ARNIs represent a novel therapeutic class combining neprilysin inhibition’s beneficial effects with angiotensin receptor blockade.  They have emerged as preferred agents in HFrEF management, offering superior outcomes compared to traditional therapy. 

Pharmacotherapy for heart failure: HFpEF 

Management of HFpEF presents unique challenges due to limited evidence-based therapeutic options compared to HFrEF. However, recent guidelines have highlighted several pharmacotherapeutic strategies for HFpEF management, including: 

  • SGLT2Is: Like HFrEF, SGLT2Is have shown promising results in HFpEF. Studies demonstrate improvements in cardiovascular outcomes and quality of life. 
  • MRAs: While the evidence is not as robust as in HFrEF, MRAs may benefit selected patients with HFpEF, particularly those with concurrent conditions such as hypertension or volume overload. 
  • ARNIs: Although ARNIs are primarily recommended for HFrEF, emerging data suggest potential benefits in HFpEF. Further research is needed to elucidate their role in this patient population. 

Finally, implementing guideline-directed therapies in real-world clinical practice remains suboptimal. This highlights the importance of multidisciplinary care, patient education, and shared decision-making to optimize treatment outcomes.