LVAD Conditioning for Heart Failure

Overseen By John Kirk

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: STAVROS G DRAKOS

Disqualifiers: Adverse events, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

100 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to investigate the potential recovery of heart function in end-stage heart failure patients supported with a Left Ventricular Assist Device (LVAD) through applying a myocardial conditioning protocol. During myocardial conditioning, LVAD speed is reduced gradually in order to increase the work load of the heart. Multiple previous studies have shown that interventions like this may improve heart function and give patients the opportunity for a better quality of life.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment LVAD Conditioning for Heart Failure?

Research shows that using a Left Ventricular Assist Device (LVAD) can improve quality of life and long-term survival for patients with severe heart failure. Some patients even experience heart recovery, allowing for potential weaning off the device. ^{1 2 3 4 5}

Is LVAD Conditioning generally safe for humans?

Research shows that while left ventricular assist devices (LVADs) can improve survival, they are associated with risks such as strokes and other adverse events. These risks are important to consider when evaluating the safety of LVADs in humans. ^{6 7 8 9 10}

How is LVAD Conditioning treatment different from other heart failure treatments?

LVAD Conditioning is unique because it involves using a mechanical device to support the heart's function in patients with severe heart failure, providing an alternative to heart transplantation or as a bridge to it. Unlike medications, this treatment physically assists the heart in pumping blood, which can be crucial for patients with advanced heart failure. ^{5 11 12 13 14}

Research Team

Stavros Drakos, MD

Principal Investigator

University of Utah

Eligibility Criteria

This trial is for heart failure patients who are getting an LVAD implant as a temporary step before a transplant. They must be part of another study (IRB 30622) and able to give consent. People who don't understand English or have been hospitalized due to complications during earlier treatment phases cannot join.

Inclusion Criteria

Enrolled in the Effects of Mechanical Unloading on Myocardial Function and Structure study (IRB 30622)

I am diagnosed with heart failure and will get an LVAD before a transplant.

Exclusion Criteria

I or my representative do not understand spoken English.

Neither the subject nor the subject's representative is willing to provide written consent for participation

I was not hospitalized due to side effects during the initial treatment phase.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Optimum Unloading Phase

Heart failure patients undergo an optimum unloading phase with LVAD support to stabilize their condition before controlled reloading

Varies

Controlled Cardiac Reloading

Participants undergo controlled cardiac reloading through LVAD speed adjustment reductions to promote myocardial recovery

Up to 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including heart tissue analysis and echocardiography

12 months

Treatment Details

Interventions

• LVAD Conditioning

Trial Overview The study tests if adjusting the speed of the LVAD can help improve heart function by gradually increasing the heart's workload. This method, known as myocardial conditioning, could potentially enhance quality of life for those with severe heart failure.

Participant Groups

Group I: Controlled Cardiac Reloading Experimental Treatment 1 Intervention

Heart failure patients with recent LVAD implantation after an optimum unloading phase, will undergo controlled cardiac reloading through LVAD speed adjustment reductions in a controlled reloading phase

LVAD Conditioning is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Left Ventricular Assist Device for:

• Advanced heart failure
• Bridge to transplant
• Destination therapy

Approved in United States as Left Ventricular Assist Device for:

• Advanced heart failure
• Bridge to transplant
• Destination therapy

Approved in Canada as Left Ventricular Assist Device for:

• Advanced heart failure
• Bridge to transplant
• Destination therapy

Approved in Japan as Left Ventricular Assist Device for:

• Advanced heart failure
• Bridge to transplant
• Destination therapy

Who Is Running the Clinical Trial?

STAVROS G DRAKOS

Lead Sponsor

Trials

3

Recruited

600+

American Heart Association

Collaborator

Trials

352

Recruited

6,196,000+

Findings from Research

Patients on the heart transplant waiting list supported by contemporary continuous-flow LVADs have significantly lower mortality rates compared to those without LVADs, particularly in urgency statuses 1A and 1B, indicating improved outcomes with modern devices.

However, complications related to LVADs can lead to a 28% rate of status upgrades, which significantly increase mortality risk, especially in patients requiring biventricular assist devices or temporary VADs, highlighting the importance of managing these complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Morbidity and mortality in heart transplant candidates supported with mechanical circulatory support: is reappraisal of the current United network for organ sharing thoracic organ allocation policy justified? Wever-Pinzon, O., Drakos, SG., Kfoury, AG., et al.[2021]

In a study of 3,836 patients with continuous-flow LVADs, pre-operative health status was found to have a limited association with post-surgery outcomes, indicating that initial health conditions may not predict mortality or rehospitalization after LVAD implantation.

However, health status measured three months after surgery, particularly using the Kansas City Cardiomyopathy Questionnaire (KCCQ), was significantly associated with increased mortality risk, suggesting that ongoing health assessments post-LVAD could be crucial for patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of global and disease-specific health status with outcomes following continuous-flow left ventricular assist device implantation. Flint, KM., Spertus, JA., Tang, F., et al.[2018]

Left ventricular assist devices (LVADs) have significantly improved the quality of life and long-term survival rates for patients with heart failure, addressing a critical health issue.

The latest LVAD models are designed to be smaller and more efficient, leading to fewer adverse events and better durability, but careful patient selection is essential for achieving the best outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges and Future Directions in Left Ventricular Assist Device Therapy. Kanwar, MK., Bailey, S., Murali, S.[2018]

A study of 26 patients who underwent LVAD explantation showed that using a standardized weaning protocol and a minimally invasive technique resulted in good long-term survival rates, with 88% survival at 1 year and 77% at 6 years.

The average left ventricular ejection fraction improved to 44.25% one year after explantation, indicating potential myocardial recovery in patients after long-term LVAD support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A detailed explantation assessment protocol for patients with left ventricular assist devices with myocardial recovery. Monteagudo Vela, M., Rial Bastón, V., Panoulas, V., et al.[2022]

In a study of 430 patients implanted with left ventricular assist devices (LVADs) in the Netherlands, long-term survival rates were over 50% after 5 years, with better outcomes for those receiving the device as a bridge to transplant compared to destination therapy.

Major adverse events, particularly infections and bleeding, were common but showed a decrease with the use of the HeartMate 3 LVAD, indicating improvements in safety with contemporary devices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left ventricular assist device implantation and clinical outcomes in the Netherlands. Damman, K., Caliskan, K., Birim, O., et al.[2023]

In a study of 6205 patients with centrifugal-flow left ventricular assist devices, the Abbott HeartMate3 (HM3) showed a significantly lower incidence of major neurologic adverse events (NAEs) compared to the Medtronic HeartWare HVAD, with rates of 6.4% versus 16.4%, respectively.

The increased risk of NAEs with the HVAD persisted beyond the early post-implantation period, indicating that patients with this device had a 5.71 times higher hazard of experiencing major NAEs during the constant hazard phase compared to those with the HM3.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebrovascular Events in Patients With Centrifugal-Flow Left Ventricular Assist Devices: Propensity Score-Matched Analysis From the Intermacs Registry. Cho, SM., Mehaffey, JH., Meyers, SL., et al.[2021]

In a study of 6205 patients with centrifugal-flow left ventricular assist devices, the Abbott HeartMate3 (HM3) showed a significantly lower incidence of major neurologic adverse events (NAEs) compared to the Medtronic HeartWare HVAD, with rates of 6.4% versus 16.4%, respectively.

The increased risk of NAEs with the HVAD persisted beyond the early post-implantation period, indicating that patients with this device had a 5.71 times higher hazard of experiencing major NAEs during the constant hazard phase compared to those with the HM3.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebrovascular Events in Patients With Centrifugal-Flow Left Ventricular Assist Devices: Propensity Score-Matched Analysis From the Intermacs Registry. Cho, SM., Mehaffey, JH., Meyers, SL., et al.[2021]

In a study of 734 patients implanted with continuous-flow left ventricular assist devices (LVADs), the HeartWare HVAD was associated with a significantly higher risk of stroke compared to the HeartMate II (HR: 1.8), indicating a safety concern for patients using this device.

Overall mortality rates were similar between the two devices (7.3% for HMII and 7.5% for HVAD), but the analysis revealed that while gastrointestinal bleeding and infections were comparable, the HVAD showed a concerning trend of increased stroke risk over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in contemporary continuous-flow left ventricular assist devices: A multi-institutional comparison shows significant differences. Stulak, JM., Davis, ME., Haglund, N., et al.[2015]

In a study of six patients who underwent a device upgrade to the HeartMate 3™ LVAD, the three-year survival rate was 100%, indicating excellent safety and efficacy of the new device.

While the HeartMate 3™ showed superior hemocompatibility and reduced pump thrombosis, there was a high risk of local re-infection in patients who exchanged their devices due to severe infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-year follow-up after less-invasive left ventricular assist device exchange to HeartMate 3™. Hanke, JS., Mariani, S., Merzah, AS., et al.[2022]

In a study of 9,489 patients receiving continuous flow left ventricular assist devices (LVADs), 16% experienced strokes within the first two years, with significant mortality risks associated with both ischemic and hemorrhagic strokes.

The study found that disabling strokes led to a much higher mortality rate, with only 70% survival after an ischemic stroke and less than 50% after a hemorrhagic stroke, highlighting the critical need for effective stroke prevention strategies in LVAD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantifying the impact from stroke during support with continuous flow ventricular assist devices: An STS INTERMACS analysis. Kirklin, JK., Naftel, DC., Myers, SL., et al.[2021]

Left ventricular assist devices (LVADs) are crucial for providing mechanical support to patients suffering from end-stage heart failure, helping to improve their quality of life and survival rates.

As LVADs become more common, it is essential for healthcare providers to understand how these devices work, the potential complications that may arise, and effective management strategies for patients using them.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical considerations for the evaluation of patients with left ventricular assist devices. McMullen, L., Barker, K., Fried, J., et al.[2023]

Patients with end-stage renal disease (ESRD) who received left ventricular assist devices (LVADs) had a significantly higher risk of death compared to those without ESRD, with 81.9% of ESRD patients dying during follow-up, often within just 16 days after surgery.

The study highlights the extremely poor prognosis for ESRD patients undergoing LVAD placement, emphasizing the need for careful consideration and shared decision-making regarding treatment options for advanced heart failure in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes Associated With Left Ventricular Assist Devices Among Recipients With and Without End-stage Renal Disease. Bansal, N., Hailpern, SM., Katz, R., et al.[2019]

In a study of 652 patients, 74 elderly patients (aged 70 and older) received left ventricular assist devices (LVADs) as a viable treatment option for heart failure, showing that LVAD implantation can be safely performed in this age group.

Elderly patients experienced similar rates of complications and mid-term survival compared to younger patients, indicating that age alone should not be a barrier to LVAD therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Septuagenarian population has similar survival and outcomes to younger patients after left ventricular assist device implantation. Galand, V., Flécher, E., Chabanne, C., et al.[2020]

In a case series of 6 patients with left ventricular assist devices (LVADs) who underwent percutaneous coronary intervention (PCI), the procedures were performed without any acute complications, indicating a level of safety in this high-risk population.

However, the study highlighted significant risks, including fatal gastrointestinal bleeding and intractable ventricular tachycardia, particularly related to the use of combined antiplatelet and anticoagulation therapies, suggesting that while PCI can be performed, its benefits may be limited and further research is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PCI in Patients Supported With CF-LVADs: Indications, Safety, and Outcomes. Anyanwu, EC., Ota, T., Sayer, G., et al.[2017]

References

1. United States pubmed.ncbi.nlm.nih.gov

Morbidity and mortality in heart transplant candidates supported with mechanical circulatory support: is reappraisal of the current United network for organ sharing thoracic organ allocation policy justified? [2021]

2. England pubmed.ncbi.nlm.nih.gov

Association of global and disease-specific health status with outcomes following continuous-flow left ventricular assist device implantation. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Challenges and Future Directions in Left Ventricular Assist Device Therapy. [2018]

4. England pubmed.ncbi.nlm.nih.gov

A detailed explantation assessment protocol for patients with left ventricular assist devices with myocardial recovery. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Left ventricular assist device implantation and clinical outcomes in the Netherlands. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Cerebrovascular Events in Patients With Centrifugal-Flow Left Ventricular Assist Devices: Propensity Score-Matched Analysis From the Intermacs Registry. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Cerebrovascular Events in Patients With Centrifugal-Flow Left Ventricular Assist Devices: Propensity Score-Matched Analysis From the Intermacs Registry. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Adverse events in contemporary continuous-flow left ventricular assist devices: A multi-institutional comparison shows significant differences. [2015]

9. Italy pubmed.ncbi.nlm.nih.gov

Three-year follow-up after less-invasive left ventricular assist device exchange to HeartMate 3™. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Quantifying the impact from stroke during support with continuous flow ventricular assist devices: An STS INTERMACS analysis. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Clinical considerations for the evaluation of patients with left ventricular assist devices. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

Outcomes Associated With Left Ventricular Assist Devices Among Recipients With and Without End-stage Renal Disease. [2019]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Septuagenarian population has similar survival and outcomes to younger patients after left ventricular assist device implantation. [2020]

14. United States pubmed.ncbi.nlm.nih.gov

PCI in Patients Supported With CF-LVADs: Indications, Safety, and Outcomes. [2017]