Heart Failure: Epidemiology, Pathophysiology, and Management.

Area of Science:

• Cardiology
• Molecular Biology
• Biochemistry

Background:

• Heart failure (HF) is a major global health burden with high mortality and rehospitalization rates.
• Current HF guidelines and management strategies have limited impact on improving patient outcomes.
• Understanding the complex mechanisms underlying HF is crucial for developing effective interventions.

Purpose of the Study:

• To synthesize HF epidemiology and systematically map calcium handling differences in physiological and pathological states.
• To analyze calcium homeostasis dysregulation across major HF subtypes: heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF).
• To integrate alterations in calcium-regulating proteins and pathways into a network model linking Ca2+ dynamics with inflammation, oxidative stress, and mitochondrial dysfunction.

Main Methods:

• Systematic review and synthesis of HF epidemiology.
• Mapping of calcium-handling differences and homeostasis dysregulation in HF subtypes.
• Development of a network model integrating calcium dynamics with related cellular processes.

Main Results:

• Identified distinct calcium-handling abnormalities in HFrEF and HFpEF.
• Summarized key alterations in calcium-regulating proteins and pathways.
• Established a network model connecting Ca2+ dysregulation to inflammation, oxidative stress, and mitochondrial dysfunction in HF.

Conclusions:

• Calcium homeostasis dysregulation is a central mechanism in HF pathogenesis.
• The developed network model provides a framework for understanding HF pathophysiology.
• Targeting specific calcium-related mechanisms offers potential for novel HF therapies and improved management.