Podcast- Ellen T. Roche, PHD- #MIT #massachusettsinstituteoftechnology # CardiacPhysiology #Hemodynamics #HeartFailur...

New methods to cardiac device design have been the focus of Ellen Roche's research. She worked in industry on embolic carotid filters, drug-eluting coronary stents, and delivery systems for trans-aortic valve bioprostheses. In this video Ellen discusses the Device-Based Solutions to Improve Cardiac Physiology and Hemodynamics in Heart Failure With Preserved Ejection Fraction.

Link to Article- https://www.jacc.org/doi/10.1016/j.jacbts.2021.06.002

• About half of patients who present with heart failure symptoms have heart failure with maintained ejection fraction.
• Clinical trials have not definitively proved that pharmacologic therapy reduces morbidity and mortality.

• Despite the fact that it is a hotly debated topic, no device-based therapy for heart failure with intact ejection fraction has been approved by the FDA.

• Atrial shunts, left ventricular expanders, mechanical circulatory support devices, and neurostimulators are all in the development stages.

Summary

Heart failure with preserved ejection fraction (HFpEF) has prompted the widespread development of device-based treatments due to its fast rising prevalence, high mortality and rehospitalization rates, and inadequacy of pharmaceutical therapy. HFpEF is a multifactorial disease with a variety of etiologies and phenotypes, characterized by decreased ventricular compliance, diastolic dysfunction, and heart failure symptoms despite normal ejection performance; these symptoms include pulmonary hypertension, limited cardiac reserve, autonomic imbalance, and exercise intolerance. Several forms of atrial shunts, left ventricular expanders, stimulation-based treatments, and mechanical circulatory support devices are now in development with the goal of treating the related mechanical or hemodynamic features to target one or more of these symptoms. Despite the fact that the majority of these options have showed promise in clinical or preclinical trials, no device-based therapy for the treatment of patients with HFpEF has yet to be authorized. The goal of this study is to go through the rationale behind each of these devices, as well as the results of the early testing phases, as well as the constraints and obstacles that come with clinical translation.

Introduction

Heart failure (HF) is a leading cause of death globally, resulting from the heart's inability to pump enough blood or fill sufficiently to meet the body's metabolic demands. It has a variety of etiologies, including cardiovascular illnesses, systemic morbidity, and genetic problems, and it is clinically identifiable by a wide range of symptoms caused by molecular, structural, and functional cardiac abnormalities (1,2).



Based on the left ventricular ejection fraction (LVEF), there are two basic phenotypes of HF: 1) HF with reduced ejection fraction (HFrEF) and 2) HF with preserved ejection fraction (HFpEF) (HFpEF). They are distinguished by LVEFs of 40 percent and 50 percent, respectively (3-6). The European Society of Cardiology's HF recommendations were updated to include a third phenotype of HF, HF with mid-range ejection fraction (HFmEF), which is defined by an LVEF of 40% to 49%. (7). Patients with HFmEF have developed as a borderline population since they were historically either excluded from the great majority of treatment trials for HF or included with categories with LVEF 40% or LVEF >49%. (8). Patients with HFmEF have a comparable risk of acquiring diabetes and atrial fibrillation as those with HFpEF, which is higher than those with HFrEF, according to recent studies. Patients with HFrEF and HFmEF, on the other hand, have a higher risk of ischemic heart disease than those with HFpEF (9).



Despite the fact that each kind of HF has its own set of demographic factors, comorbidities, and therapeutic responses, research has long been concentrated on HFrEF (5,10). Despite this, the prevalence of HFpEF has been significantly increasing in recent decades, owing to an increase in life expectancy, an increase in the prevalence of metabolic diseases commonly linked with this condition, and a lack of effective treatments (5,11-14). As a result, it is estimated that over 3 million people in the United States are affected by HFpEF, which has emerged as the most common kind of HF and a serious public health issue (5,15). Although it is difficult to assess the economic impact of HFpEF, the total medical cost of HF in the United States is expected to reach $53.1 billion by 2030. (16). Because HFpEF today accounts for around half of all occurrences of HF (12), and assuming that this is still the case by 2030, a total medical expenditure of $26.55 billion is predicted, with $21.24 billion spent on hospitalization.



Hypertension (80-90%) and obesity (60-75%) are both known to be substantial risk factors for HFpEF (5), since they both cause a systemic pro-inflammatory response that leads to cardiac remodeling and ventricular hypertrophy (17). Furthermore, the former causes a state of pressure overload, which alters left ventricular (LV) biomechanics (as discussed in the following section), whereas the latter is linked to defects in fuel utilization and efficiency, lipotoxicity, and the loss of cytoprotective signaling (as discussed in the following section) (18). (19). All of these pathways are thought to exacerbate myocardial fibrosis in people with HFpEF. Aging, coronary artery disease, diabetes mellitus, chronic renal disease, pulmonary hypertension, chronic obstructive pulmonary disease, and anemia are all comorbidities that have a role in illness initiation and progression (10,17,20).



The variability of illness symptoms, the lack of consensus on diagnostic guidelines, and the lack of a solid animal model have all hampered our present understanding of HFpEF pathogenesis (21). As a result, patients with HFpEF have a survival rate that is comparable to that of HFrEF but lower than that of most malignancies (10,12). To present, the majority of pharmacologic medicines studied in clinical trials have yielded unsatisfactory outcomes for the treatment of HFpEF, which is still mostly focused on exercise and the use of diuretics and mineralocorticoid antagonists to manage congestion symptoms and associated comorbidities (5).



The four primary kinds of device-based options for the treatment of HFpEF include atrial shunts, LV expanders, electrical and neurostimulators, and mechanical circulatory support (MCS) devices. Although none of these devices has yet been licensed for clinical use in the United States, evidence from randomized clinical trials and preclinical testing are positive, giving hope that they will one day transform HFpEF therapy and improve patients' survival and quality of life (QoL).