Congestive heart failure (CHF) represents a complex clinical syndrome characterized by the heart's inability to pump blood effectively to meet the body's metabolic demands. Central to the pathophysiology of CHF is the dysregulation of calcium homeostasis, which plays a fundamental role in excitation-contraction coupling and cardiac performance. This comprehensive review examines the intricate relationship between altered calcium handling and the development and progression of CHF, with particular emphasis on its implications for coronary artery disease (CAD). The review synthesizes current literature to elucidate the molecular mechanisms underlying calcium dysregulation in failing hearts, explores the bidirectional relationship between calcium homeostasis and coronary artery function, and evaluates emerging therapeutic strategies targeting calcium-handling proteins. Key findings indicate that impaired calcium cycling, involving dysfunction of the sarcoplasmic reticulum calcium ATPase, ryanodine receptors, and L-type calcium channels, contributes significantly to contractile dysfunction and arrhythmogenesis in CHF. Furthermore, the interplay between calcium homeostasis and CAD creates a pathophysiological cycle that exacerbates both conditions. Understanding these mechanisms is crucial for developing targeted therapeutic interventions that can improve cardiac function, reduce symptoms, and enhance survival in patients with CHF and concurrent CAD. Future research directions should focus on personalized approaches to calcium modulation and the development of novel therapeutic targets within the calcium-handling machinery.
Calcium homeostasis, congestive heart failure, coronary artery disease, excitation-contraction coupling, sarcoplasmic reticulum, therapeutic targets
Congestive heart failure affects over 64 million people worldwide and represents one of the leading causes of cardiovascular morbidity and mortality. The syndrome is characterized by structural and functional cardiac abnormalities that impair the heart's ability to fill with or eject blood effectively [McMurray et al., 2022; Heidenreich et al., 2023]. Central to cardiac function is the precise regulation of calcium homeostasis, which governs excitation-contraction coupling—the process by which electrical activation of cardiac myocytes leads to mechanical contraction [Bers, 2022; Eisner et al., 2023]. The relationship between calcium dysregulation and heart failure has been recognized for decades, with mounting evidence demonstrating that alterations in calcium handling contribute not only to contractile dysfunction but also to the progression of heart failure and associated arrhythmias. In the context of coronary artery disease, calcium homeostasis becomes even more complex, as ischemic conditions further compromise cellular calcium regulation and exacerbate myocardial dysfunction [Luo & Anderson, 2023; Venetucci et al., 2022]. Understanding the molecular mechanisms underlying calcium dysregulation in heart failure has significant therapeutic implications. Current pharmacological interventions for heart failure, including ACE inhibitors, beta-blockers, and aldosterone receptor antagonists, while effective in improving outcomes, do not directly target the fundamental calcium-handling abnormalities that characterize the failing heart [Savarese et al., 2023; Rosano et al., 2022]. This review aims to provide a comprehensive analysis of the current understanding of calcium homeostasis in congestive heart failure, its relationship with coronary artery disease, and the potential for developing targeted therapeutic strategies.
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Arnab Roy
Corresponding author
Sai Nath University, Ranchi, Jharkhand-835219, India
Mahesh Kumar Yadav
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Naba Kishor Gorai
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Rakhi Kumari
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Megha Chattaraj
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Tammana Parween
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Pinky Kumari
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Divya Kumari
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Bhumika Kumari
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Ronit Tirkey
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Karan Kumar
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Nitish Kumar Verma
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Abhishek Verma
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Rahul Kumar Verma
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Shweta Kumari
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Purnima Kumari
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Mona Singh
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Sunny Kumar
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Ved Prakash Singh
Co-author
Sai Nath University, Ranchi, Jharkhand-835219, India
Mahesh Kumar Yadav, Naba Kishor Gorai, Rakhi Kumari, Megha Chattaraj, Tammana Parween, Pinky Kumari, Divya Kumari, Bhumika Kumari, Ronit Tirkey, Karan Kumar, Nitish Kumar Verma, Abhishek Verma, Rahul Kumar Verma, Shweta Kumari, Purnima Kumari, Mona Singh, Sunny Kumar, Ved Prakash Singh, Arnab Roy*, The Interplay Between Calcium Homeostasis and Cardiac Function in Congestive Heart Failure: Implications for Coronary Artery Disease, Int. J. Sci. R. Tech., 2025, 2 (8), 420-434. https://doi.org/10.5281/zenodo.16978272
10.5281/zenodo.16978272