Avenues for optimization of cardiac therapeutics by minimally invasive delivery

In the past 20 years, minimally invasive delivery strategies have emerged to bridge the therapeutic gap between highly invasive surgery and less efficient nonsurgical approaches. New, less invasive technologies, including vascular, transendocardial, thoracoscopic, and inhalation delivery methods, can enhance cardiac targeting, promote drug retention, and minimize trauma compared to conventional interventions. Understanding current therapeutic agents, including biomolecules, biomaterials, and medical devices, along with their respective mechanisms, is essential for optimizing minimally invasive delivery strategies. Despite current therapeutic promises, dynamic heart motion and low delivery efficiency hinder the clinical translation of minimally invasive heart repair. Future studies should aim to address these hurdles by optimizing cardiac uptake, advancing personalized medicine, and developing safer delivery tools. To map the state of the field and its future potential, this review summarizes several minimally invasive cardiac delivery approaches and how to leverage existing techniques in concert to harness the impact of minimally invasive cardiac delivery. STATEMENT OF SIGNIFICANCE: Minimally invasive cardiac delivery techniques represent an important advancement in treating heart diseases, bridging the gap between invasive surgeries and less effective nonsurgical methods. Unlike traditional approaches, these novel methods, including vascular, transendocardial, thoracoscopic, and inhalation techniques, provide targeted drug delivery directly to the heart while reducing trauma. This review uniquely synthesizes current advancements in delivering therapeutic agents such as biomolecules and medical devices, highlighting their improved cardiac targeting and retention capabilities. It identifies critical challenges, including the heart's motion and low delivery efficiency, and discusses opportunities for innovation. Addressing these challenges can significantly impact patient outcomes, enhance personalized treatments, and advance the broader field of minimally invasive cardiovascular medicine.