AMMIRATI, GIUSEPPE (2025) From Mechanisms to Outcomes: Translational Advances in Heart Failure and Atrial Fibrillation Management. [Tesi di dottorato]

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Abstract

Cardiac electrophysiology has evolved from a purely interventional discipline focused on arrhythmia suppression into a multifaceted field that integrates device- based, pharmacological, and digital innovations to optimize patient outcomes. Atrial fibrillation (AF) and heart failure (HF) represent two of the most prevalent and interconnected cardiovascular conditions, often coexisting and sharing pathophysiological mechanisms such as structural remodeling, neurohormonal activation, and electrical instability. Their intersection poses major clinical and therapeutic challenges, demanding a comprehensive and multidisciplinary approach. Over the past decade, remarkable progress has been achieved through the refinement of device therapy—including cardiac resynchronization therapy (CRT), implantable cardioverter defibrillators (ICD), and left atrial appendage occlusion (LAAO)— alongside the advent of new pharmacological classes such as angiotensin receptor– neprilysin inhibitors (ARNi) and sodium–glucose co-transporter 2 inhibitors (SGLT2i). These agents have redefined the treatment paradigm for heart failure with reduced ejection fraction (HFrEF), contributing to mortality reduction and improved functional status. Yet, how these drugs interact with and potentially potentiate device therapy remains an area of active investigation. Simultaneously, electrophysiological procedures have been profoundly reshaped by technological innovation. Artificial intelligence (AI)–driven algorithms, intracardiac echocardiography (ICE)–guided mapping, ablation index–guided lesion creation, and emerging energy sources such as pulsed field ablation (PFA) are transforming procedural workflows, enhancing precision, and improving safety. These innovations are steadily redefining the standards of catheter ablation and may pave the way toward fully image- and data-guided electrophysiology. In parallel, stroke prevention strategies have expanded beyond oral anticoagulation. LAAO has emerged as a viable alternative for patients with contraindications to long-term anticoagulation and as a complementary approach in rhythm control strategies. In particular, the interplay between LAA electrical isolation (LAAEI) and subsequent occlusion has raised important questions regarding optimal timing and procedural sequencing, especially in complex AF substrates. The following thesis reflects a three-year scientific and training journey focused on the intersection of these evolving domains. It encompasses clinical and translational studies spanning from heart failure therapy and device optimization to AI-driven ablation and stroke prevention, with the unifying goal of improving outcomes in patients with arrhythmias and advanced cardiac disease.

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