Valvular Heart Disease: Moving Towards Translational Medicine

 Understanding of the molecular mechanisms of cardiac diseases has greatly improved over the last several decades, leading to a variety of evidence-based treatments and recommendations for screening and medical management.^1-3 Particularly in the context of cardiomyopathies, arrhythmias, thoracic aortic aneurysms and dissections, and lipid disorders, advancements in human genetics have led to important recommendations related to implications for management and treatment of the individual patient and family members.⁴ Valvular heart disease is another significant cardiovascular cause of morbidity and mortality, but knowledge of the molecular underpinnings as well as availability of non-invasive therapeutic options to prevent or slow the progression of disease remain a challenge for clinical care. Development of a strong evidence-base for valvular heart disease may help to identify therapeutic targets and potential medical interventions, improve patient risk assessment and diagnostic capabilities, and ultimately may be used for future medical management guidelines.

 The scientific statement by Dr. Small and colleagues is very timely, especially with an aging population at risk for developing valvular heart disease and the continued rising costs of currently available treatments.⁵ The authors of this scientific statement synthesize years of data to describe what is currently known about common valvular heart conditions including diseases of aortic valve leaflets, primary mitral valve disease, and right sided valvular heart disease. As described in this scientific statement, valvular heart disease represents a wide range of conditions that can be individually complicated and may or may not have additional findings (such as in the case of a manifestation in a syndromic condition). For many valvular heart diseases, the molecular etiologies are not well understood, or only partially understood for a subset of the population with the condition, which impacts the availability of possible therapeutic interventions.

 While there continues to be progress in the understanding of the molecular and cellular mechanisms of valvular heart disease, this scientific statement highlights the gaps in knowledge that still remain as barriers to the advancement of clinical care in this disease context. Importantly, the authors discuss the critical need to identify primary drivers in the early development of valvular heart disease, which are necessary to identify potential preventive interventions. This is especially of interest in the precision medicine and preventive care context, as early identification and disease prevention and/or effective treatment to reduce morbidity and mortality are important tenants for advancing public health. In addition, the authors of the scientific statement discuss the need for improvement of imaging and diagnostic modalities and development of medical therapies to slow or halt progression of disease.

The currently available evidence does not allow for presentation of comprehensive gene lists for clinical testing consideration or effective preventative or therapeutic management recommendations across valvular heart diseases. Instead, this scientific statement presents research priorities across several domains of valvular heart disease including calcific aortic valve disease, bicuspid aortic valve disease, mitral valve prolapse, and rheumatic heart disease. These research priorities may be especially useful for researchers considering pursuing work in the valvular heart disease context. In addition, the authors hope that these research priorities will be considered by funding agencies for research submissions to advance valvular heart disease research. Funding agencies might also consider a range of methodologies to investigate these current knowledge gaps. In the era of big data, omics research, and the development of emerging tools to bridge multiple data sources, technological advancements and new analytic methodologies may allow for investigation of some of these unanswered questions. For several of the identified knowledge gaps and research priorities, the authors discuss the importance of large human studies, longitudinal population-based studies, genomic studies, and studies investigating epidemiologic factors. Furthermore, the need for basic science research is imperative for advancement of our knowledge in this domain. For example, the authors point out the need for funded basic science infrastructure supporting the development of organic and inorganic models of heart tissue for addressing gaps in knowledge of calcific aortic valve disease.

 Equal in importance to efforts to improve our molecular understanding of valvular heart disease is the need for development of evidence-based applications of that knowledge. There can be many challenges inherent in transitioning scientific discoveries into effective strategies for preventing and treating disease, and the subsequent translation to everyday clinical care and health decision making.⁶ As knowledge gaps are addressed and the proposed research priorities from this scientific statement continue to be investigated, the engagement of multidisciplinary experts such as cardiologists, genetics and genomics specialists, and other subject matter specialists will be important in the proper translation of findings to effective and safe medical management.^7,8 The authors of the scientific statement also recognize the need for consideration of equitable access to subsequent prevention and treatment of valvular heart disease. For example, they discuss considering factors such as cost, distribution, storage, and administration of candidate drug targets. As such, studies investigating the translation of knowledge products to effective and equitable clinical care should also be a priority for future research in the context of valvular heart disease.

 In summary, this AHA scientific statement provides valuable information about the current state of knowledge related to common valvular heart disease and paves the way for translational science advancement by describing gaps in the literature and priority research areas. The prioritization of research areas in valvular heart disease is not only helpful for current and future researchers, but may be considered for use by funding agencies for research submissions. Addressing the current knowledge gaps in valvular heart disease will be an important first step in the translation to effective, safe, and equitable improvements in clinical care.