Microvascular and lymphatic dysfunction in HFpEF and its associated comorbidities.

Area of Science:

• Cardiology
• Pathophysiology
• Vascular Biology

Background:

• Heart failure with preserved ejection fraction (HFpEF) is a complex condition with limited understanding and treatment options.
• HFpEF is characterized by diastolic dysfunction, cardiac remodeling, and increasingly recognized roles for microvascular dysfunction and inflammation.
• Recent research suggests generalized lymphatic dysfunction in experimental models linked to HFpEF risk factors like obesity and diabetes.

Purpose of the Study:

• To review the combined role of coronary (micro)vascular dysfunction and lymphatic alterations in HFpEF pathogenesis.
• To explore how these dysfunctions contribute to reduced cardiac perfusion, inflammation, edema, and metabolic changes in HFpEF.
• To focus on HFpEF associated with metabolic risk factors including obesity, type 2 diabetes mellitus (T2DM), hypertension, and aging.

Main Methods:

• Literature review of recent studies on HFpEF pathophysiology.
• Analysis of evidence linking microvascular and lymphatic dysfunction to HFpEF development.
• Synthesis of findings related to metabolic risk factors and their impact on cardiac function.

Main Results:

• Coronary microvascular dysfunction and lymphatic alterations are implicated in key HFpEF pathological steps.
• These dysfunctions contribute to reduced cardiac perfusion, chronic inflammation, and myocardial edema.
• Impacts include altered cardiac metabolism, fibrosis, and cardiomyocyte stiffness, particularly in metabolically compromised individuals.

Conclusions:

• Combined microvascular and lymphatic dysfunction plays a significant role in the pathophysiology of HFpEF.
• Understanding these mechanisms is crucial for developing targeted prevention and treatment strategies for HFpEF, especially in patients with metabolic risk factors.
• Further research is warranted to elucidate the precise interactions and therapeutic targets.