Heart Failure: Epidemiology, Pathophysiology, and Management

Abstract

Heart failure (HF) is one of the leading causes of hospitalization and mortality worldwide. Despite continuous updates to modern clinical guidelines regarding HF classification and management, mortality and rehospitalization rates remain persistently high. Enhancing the prevention and treatment of HF therefore represents a major challenge both now and in the future. In this review, we synthesize HF epidemiology and systematically mapped the calcium‑handling differences under physiological and pathological conditions, as well as the patterns of calcium‑homeostasis dysregulation across the major HF subtypes (heart failure with reduced ejection fraction; heart failure with preserved ejection fraction). Moreover, we summarize alterations in key calcium-regulating proteins (points) and calcium homeostasis-related pathways (lines), and further integrate these nodes into a network model that links Ca²⁺ dynamics remodeling with inflammation, oxidative stress, and mitochondrial dysfunction. Building on this mechanistic network, we discuss both conventional HF management strategies and emerging therapeutic developments that target distinct mechanisms through points and lines. Finally, we outline the unmet needs and future directions across the current “diagnosis–treatment–monitoring” continuum, with the overarching goal of advancing precision diagnosis, individualized therapy, and the establishment of a comprehensive HF management framework.

Keywords

calcium homeostasis / calcium regulatory factors / calcium-related pathways / heart failure / pathological mechanism

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