The war against heart failure: the Lancet lecture

Area of Science:

• Cardiology
• Molecular Biology
• Regenerative Medicine

Background:

• Heart failure affects 38 million globally, increasing with an aging population, and has a worse prognosis than most cancers.
• It is a leading cause of hospitalization in older adults, particularly in high-income countries.
• Despite advances, significant unmet needs remain in heart failure management.

Purpose of the Study:

• To review and highlight emerging therapeutic strategies for heart failure.
• To discuss novel approaches targeting calcium handling, gene expression, and cardiac support.
• To present a multi-pronged "war on heart failure" strategy.

Main Methods:

• Enhancing myofilament sensitivity to calcium (Ca2+).
• Investigating gene therapy targeting SERCA2a and other calcium-handling proteins.
• Exploring microRNA (miRNA) targeted therapies using antagomirs.
• Evaluating cell-based therapies (bone marrow mononuclear cells, mesenchymal cells).
• Assessing long-term ventricular assistance devices as destination therapy.

Main Results:

• SERCA2a gene transfer showed promise in a phase 2 trial.
• Antagomirs improved cardiac function in animal models of heart failure.
• Cell therapies demonstrate potential in preclinical and early clinical trials.
• Ventricular assist devices are increasingly used, with some cases showing myocardial recovery and device explantation.

Conclusions:

• Multiple novel therapeutic avenues, including gene therapy, miRNA modulation, cell therapy, and mechanical support, are emerging for heart failure.
• These approaches, individually or in combination, represent significant advancements in the fight against heart failure.
• Further research and clinical trials are crucial to fully realize the potential of these innovative treatments.