Pathophysiology

In HFrEF, a reduction in cardiac output triggers compensatory mechanisms like sympathetic activation, the renin-angiotensin-aldosterone system (RAAS), and fluid retention. This aims to maintain blood pressure and end-organ perfusion initially. However, chronic neurohormonal activation promotes cardiac remodeling through mechanisms like:

• Myocyte hypertrophy and apoptosis
• Fibrosis from collagen deposition
• Impaired calcium handling

This remodeling causes detrimental changes:

• Ventricular dilation, resulting in mitral regurgitation
• Decreased contractility and higher wall stress
• Ventricular arrhythmias

ultimately leading to a progressive decline in ventricular function over time.

In HFpEF, relaxation and filling are impaired during diastole despite preserved systolic function. Underlying pathologies include:

• Abnormal ventricular stiffness from hypertension or infiltration (e.g. amyloidosis)
• Impaired calcium reuptake into the sarcoplasmic reticulum
• Extracellular matrix remodeling
• Endothelial dysfunction

Patients compensate by relying on increased filling pressures. However, small changes in volume status severely impact cardiovascular performance.

In both HFrEF and HFpEF:

• Fluid overload causes pulmonary and peripheral congestion along with dyspnea and edema.
• Reduced perfusion causes fatigue, renal dysfunction, and gastrointestinal distress.

Worsening symptoms represent decompensated HF and often require hospitalization. Chronic neurohormonal activation is central to HF progression. Optimal therapy targets neurohormonal antagonism and preventing cardiac remodeling.