Arrhythmogenic and metabolic remodelling of failing human heart
C R Gloschat1, A C Koppel1, K K Aras1
1Department of Biomedical Engineering, The George Washington University, Washington, DC, USA.
Insights
Heart failure (HF) research needs better human models. Validating animal study findings in human in vitro models is crucial for developing effective HF therapies and improving patient outcomes.
Area of Science:
- Cardiology
- Translational Medicine
- Biomedical Engineering
Background:
- Heart failure (HF) is a global health crisis with rising prevalence and incidence.
- Current treatments for HF do not halt or reverse disease progression, necessitating novel therapeutic strategies.
- Significant challenges exist in translating findings from animal models to human patients due to interspecies physiological differences.
Purpose of the Study:
- To review recent advancements in human heart failure research, focusing on key pathological changes.
- To highlight the importance of human in vitro models for validating animal study hypotheses.
- To discuss emerging technologies that can facilitate the development of improved HF therapies.
Main Methods:
- Review of recent scientific literature on human heart failure investigations.
- Analysis of translational challenges between animal models and human studies.
- Exploration of new technologies for studying HF pathophysiology in human models.
Main Results:
- Human in vitro models are essential for validating hypotheses generated from animal studies.
- Human heart investigations provide critical translational platforms for safety and efficacy testing prior to clinical trials.
- Recent research has advanced the understanding of electrophysiology, metabolic, and beta-adrenergic remodelling in human HF.
Conclusions:
- There is an urgent need for improved human-based models in heart failure research.
- Human in vitro models offer a promising avenue for accelerating the translation of basic science discoveries into clinical applications.
- New technologies are enhancing the ability to study complex HF mechanisms in human systems, paving the way for targeted therapies.
Abstract:
Heart failure (HF) is a major cause of morbidity and mortality worldwide. The global burden of HF continues to rise, with prevalence rates estimated at 1-2% and incidence approaching 5-10 per 1000 persons annually. The complex pathophysiology of HF impacts virtually all aspects of normal cardiac function - from structure and mechanics to metabolism and electrophysiology - leading to impaired mechanical contraction and sudden cardiac death. Pharmacotherapy and device therapy are the primary methods of treating HF, but neither is able to stop or reverse disease progression. Thus, there is an acute need to translate basic research into improved HF therapy. Animal model investigations are a critical component of HF research. However, the translation from cellular and animal models to the bedside is hampered by significant differences between species and among physiological scales. Our studies over the last 8 years show that hypotheses generated in animal models need to be validated in human in vitro models. Importantly, however, human heart investigations can establish translational platforms for safety and efficacy studies before embarking on costly and risky clinical trials. This review summarizes recent developments in human HF investigations of electrophysiology remodelling, metabolic remodelling, and β-adrenergic remodelling and discusses promising new technologies for HF research.
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