Bridging Treatment Gaps in Heart Failure with Reduced Ejection Fraction: Advancing Evidence for Device-Based Therapies

Heart failure with reduced ejection fraction (HFrEF) is a progressive condition affecting millions worldwide, imposing both a clinical and economic burden on patients and healthcare systems. While guideline-directed medical therapy (GDMT) remains the cornerstone of treatment, its underutilization, exacerbated by clinical inertia and the challenges of managing comorbidities, continues to limit patient outcomes 

As the disease advances, a critical gap emerges between the stabilizing effects of GDMT in the early stages and the necessity for advanced interventions like left ventricular assist devices (LVADs) or heart transplantation in pump failure. Emerging device-based therapies are now reshaping the treatment landscape, offering new solutions for structural and functional remodeling of the left ventricle (LV) and addressing unmet needs in intermediate stages of heart failure. 

To support the adoption of these therapies, clinical trials must do more than validate safety and effectiveness, they must also demonstrate reductions in mortality, hospitalizations, and disease progression to justify reimbursement. RQM+, as a leading CRO in the MedTech space, is uniquely equipped to design and execute trials that bridge these gaps. By integrating economic analyses and real-world evidence, we can help MedTech innovators align device-based therapies with payer requirements, advancing their adoption and ensuring access for patients who need them most. 

Through collaboration with MedTech innovators, RQM+ is committed to transforming the HFrEF landscape, combining pharmacologic and structural interventions to deliver improved outcomes for patients, providers, and payers alike.  

Introduction 

Managing HFrEF requires a structured, multi-phase approach, starting with GDMT. This cornerstone therapy including beta-blockers, ARNIs, MRAs, and SGLT2 inhibitors, has been proven to reduce morbidity, mortality, and hospitalizations. However, its underutilization, driven by clinical inertia, the underappreciation of risk, and the complexity of patient comorbidities, deprives many patients of its benefits.

The progression of heart failure typically follows distinct phases: an onset stage, where GDMT is most effective; a relatively stable phase, during which disease management focuses on maintaining stability; a period of episodic decompensation, where the heart progressively struggles to maintain function; and, eventually, pump failure, when advanced, expensive interventions such as left ventricular assist devices (LVADs), or heart transplantation are required. GDMT plays a critical role in the onset stage, stabilizing patients and delaying progression. However, as the disease advances, GDMT alone often becomes insufficient.

A significant gap in care exists in the transition from onset to eventual episodic decompensation. While cardiac resynchronization therapy (CRT) can help select patients, eligibility is limited, leaving a large subset of patients without viable treatment options. This gap is further compounded by clinical inertia resulting in the underutilization or delayed escalation of GDMT. Contributing factors include hesitancy to manage side effects, insufficient familiarity with therapy titration, and an underappreciation of the risks of inaction during the early stages of the disease. These challenges lead to more frequent hospitalizations, a decline in quality of life (QoL), and accelerated disease progression. Once pump failure sets in, treatment options narrow significantly. LVADs and heart transplantation are invasive, resource-intensive, and reserved for a small fraction of patients due to stringent criteria, high costs, and limited availability.

To address these gaps, greater adherence to GDMT from the onset is essential, but this alone is insufficient. The development and integration of innovative device-based therapies are critical to bridging the intermediate stages of care between disease onset and pump failure. Emerging devices such as mitral valve repair systems, intramyocardial reshaping tools, and others provide new opportunities to enhance outcomes for patients whose heart function deteriorates despite optimal GDMT.

The following sections will explore the reimbursement landscape for these device-based therapies, highlighting the importance of achieving hard clinical endpoints to justify payer support. Additionally, we will examine novel devices poised to address the intermediate gap in HFrEF care, focusing on their real-world effectiveness and measurable patient outcomes. RQM+ is committed to designing and executing trials that evaluate these therapies, demonstrating their ability to improve QoL, reduce hospitalizations, and slow disease progression, supporting broader reimbursement and access to effective treatments across all stages of heart failure.

Expanding Focus: Reimbursement Considerations for HFrEF Device-Based Therapies

Device-based therapies hold promise for addressing structural issues in heart failure management. However, achieving reimbursement requires a rigorous focus on hard clinical endpoints, beyond cost-effectiveness and QoL improvements. While the economic benefits of reduced hospitalization rates and improved QoL are compelling, payers require substantial evidence of clinical impact.

Key hard endpoints to target include:

• Reductions in mortality: Showing a direct link between device use and decreased mortality rates among HFrEF patients can provide strong justification for payer support.
• Reduced hospitalizations: Demonstrating a clear reduction in heart failure-related hospitalizations and emergency interventions will further underline the value of these devices in stabilizing high-risk patients.
• Measurable improvements in heart function: Endpoints like reductions in LV volumes, improvements in LV ejection fraction, and enhanced six-minute walk test (6-MWT) results are critical in proving that device-based interventions deliver tangible physiological benefits.

Enhancement Strategy for Reimbursement Support

• Integrate Hard Endpoints with Economic Analyses: To make a compelling case for reimbursement, future clinical trials should document both hard clinical outcomes and economic impacts, such as fewer hospitalizations and reduced long-term care needs. While cost savings alone may not suffice, pairing them with demonstrated health improvements can make a more persuasive argument.
• Prioritize Real-World Effectiveness: Given the variability in clinical trial settings versus real-world conditions, observational studies that document device effectiveness across diverse patient demographics are vital. By showing that hard endpoints are met consistently outside controlled environments, real-world evidence strengthens the case for payer coverage.

Clinical and Device-Based Innovations in HFrEF: Addressing Gaps with Evidence-Driven Reimbursement Support

Emerging device therapies including partitioning devices, reshaping tools, and mechanical support systems are poised to bridge intermediate gaps in care, demonstrating measurable improvements in patient outcomes and QoL. While these benefits are promising, achieving consistent reimbursement requires hard clinical endpoints (not only surrogate endpoints) that demonstrate substantial impact on patient outcomes. The following is a brief analysis of each device, along with proposed trials to validate their clinical and economic value.

1. V-Sling System: Targeting LV dilation and wall stress, the V-Sling aims to restore normal LV shape and prevent further remodeling, complementing GDMT in cases of refractory heart failure.
   • Pros: Demonstrated efficacy in reducing LV volume with a relatively straightforward implantation procedure.
   • Cons: Potential issues with mechanical anchoring and long-term durability.
   • Trial Suggestion: A study integrating hard clinical endpoints, such as reductions in hospitalization rates and mortality, alongside economic data could highlight the V-Sling’s role in stabilizing high-risk patients and reinforce its value to payers.
2. MIRTH (Myocardial Intramural Remodeling by Transvenous TeTHer): Designed to reshape the LV from within, MIRTH is a structural solution for dilated cardiomyopathy that avoids impact on the right ventricle.
   • Pros: Offers targeted reshaping with minimal procedural invasiveness, addressing the structural progression of HFrEF.
   • Cons: Limited human data; primarily supported by animal studies and early clinical trials.
   • Trial Suggestion: A trial comparing MIRTH plus GDMT to GDMT alone could establish its effectiveness in achieving endpoints like reductions in LV volumes and mortality, which are essential for payer support.
3. Carillon Mitral Contour System: A percutaneous device for mitral valve repair, Carillon has shown improvement in LV function and reduced functional mitral regurgitation, enhancing both exercise capacity and quality of life.
   • Pros: Minimally invasive with low procedural risk.
   • Cons: Limited applicability for patients without FMR.
   • Trial Suggestion: A payer-focused study assessing Carillon’s impact on six-minute walk test (6MWT) results, LV volumes, and hospitalization rates could help establish its value by focusing on hard endpoints and real-world effectiveness.
4. ContraBand Pulmonary Artery Banding: This device regulates LV filling pressures via pulmonary artery banding, supporting patients with chronic HFrEF and DCM.
   • Pros: Demonstrated improvements in exercise tolerance and hemodynamics.
   • Cons: Limited suitability for patients with significant pulmonary hypertension.
   • Trial Suggestion: A study demonstrating ContraBand’s effects on hard endpoints, such as reductions in hospitalizations and functional improvements, would provide valuable data for clinical adoption and reimbursement support.
5. AccuCinch Ventricular Restoration System: Utilizing an anchor-and-tether system, AccuCinch reduces LV dilation and wall stress. Early data indicate improvements in LV ejection fraction and hospitalization rates.
   • Pros: Durable LV volume reduction with a low adverse event rate.
   • Cons: Requires large-bore access and advanced procedural expertise.
   • Trial Suggestion: A multicenter study measuring hospitalization reduction, LV function improvements, and economic benefits could strengthen the case for reimbursement by showcasing both clinical and economic impacts.

Proposed Clinical Trial Initiatives for HFrEF

1. Integrated Multi-Device and GDMT Synergy Trials: Given the unique potential of device therapies to complement GDMT, multi-arm trials can help identify the most effective layered treatment strategies. A trial comparing GDMT alone, GDMT with the Carillon Mitral Contour System, and GDMT with AccuCinch would assess how combined therapies influence outcomes such as LV volume reduction, ejection fraction improvements, and overall mortality. Emphasizing hard clinical endpoints in these trials could demonstrate each combination’s value and establish best practices for layering pharmacologic and structural interventions.
2. Real-World Effectiveness and Reimbursement Support Trials: By focusing on real-world effectiveness and economic outcomes, such as reductions in hospitalizations, emergency interventions, and healthcare utilization, these trials can generate critical data for payers. Incorporating metrics like quality-adjusted life years (QALYs) gained, reductions in readmissions, and long-term cost savings will make a strong case for reimbursement. Real-world data documenting consistent achievement of hard clinical endpoints across diverse demographics will underscore these therapies’ reliability outside controlled settings, bolstering support from both payers and clinicians.
3. Longitudinal Outcomes and Durability Studies: Tracking patients over a 3-5 year period post-implantation with comprehensive GDMT can provide valuable insights into the long-term durability and effectiveness of these device-based therapies. By assessing hard endpoints such as sustained improvements in LV function, reduction in mortality, and fewer rehospitalizations, these longitudinal studies will build the evidence base needed to establish these devices as standard care, reinforcing their value proposition to both clinicians and payers.
4. Patient-Centered Outcome Trials: Highlighting patient-reported outcomes (PROs) is essential to align clinical goals with patient needs and payer priorities. Trials focusing on meaningful, patient-centered metrics—such as improvements in Kansas City Cardiomyopathy Questionnaire (KCCQ) scores, New York Heart Association (NYHA) classifications, and functional capacity (e.g., 6-MWT), can demonstrate tangible quality-of-life benefits. These outcomes resonate strongly with payers, providing a comprehensive view of device impact that includes both clinical and patient benefit-centric gains, facilitating broader adoption and coverage.
5. Comparative Economic and Clinical Benefit Analyses: Given the significant cost disparity between pharmacologic and device-based therapies, it is essential to demonstrate not only clinical improvements but also how these benefits translate into economic value. A trial comparing hard clinical endpoints and associated healthcare costs among patients receiving GDMT alone versus those receiving layered device therapies could highlight cost offsets through reduced hospitalizations and emergency care. Demonstrating that devices can offer durable clinical benefits with justifiable economic impact is crucial for securing reimbursement.

Conclusion

The combination of GDMT and innovative device-based therapies holds transformative potential for redefining care in HFrEF. By addressing critical gaps in treatment, these therapies offer an opportunity to significantly improve patient outcomes while meeting the demands of modern healthcare systems.

RQM+ is uniquely positioned to partner with MedTech innovators in designing and executing trials that go beyond validation, focusing on hard clinical endpoints, real-world effectiveness, and economic analyses that resonate with payers. Through our patient-centered, evidence-driven approach, we aim to establish these therapies as valuable and reimbursable options in the HFrEF landscape, ensuring broader access to life-changing interventions.

With expertise spanning clinical innovation, regulatory strategy, and economic viability, RQM+ provides the strategic and technical capabilities to accelerate the journey from innovation to implementation. Together with our MedTech partners, we can shape a new paradigm in HFrEF care, one that seamlessly integrates pharmacologic and structural solutions to deliver exceptional outcomes and transform the lives of patients around the world.