CRT Optimization for Heart Failure

Recruiting at 1 trial location

Overseen By Christopher D Brown

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Allina Health System

Disqualifiers: Decompensated heart failure, Pregnancy, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

40 Participants Needed

Trial Summary

What is the purpose of this trial?

Cardiac resynchronization therapy (CRT), or atrial-synchronized biventricular (BiV) pacing, is an FDA-approved device therapy option for heart failure (HF) patients with reduced left ventricular ejection fraction and electrical dyssynchrony. A traditional CRT device has pacing leads implanted within the right atrium (RA), the right ventricle (RV), and within a coronary vein overlying the lateral or posterior left ventricle (LV). Within the past decade, various multi-center randomized controlled trials have reported improved quality of life, aerobic exercise capacity, LV systolic function and structure, as well as decreased hospitalization rates and mortality among patients with HF. Despite improvements in CRT technology with multipoint pacing, quadripolar leads, and adaptive pacing algorithms, approximately 30% of patients do not clinically benefit and are considered non-responders. This study looks to optimize CRT device programming in patients considered non-responders to CRTusing information obtained from standard ECG machines, and to assess acute and chronic effects of CRT optimization using cardiac magnetic resonance imaging (CMR).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires participants to be on standard medical therapy. It's best to discuss your specific medications with the trial team.

What data supports the idea that CRT Optimization for Heart Failure is an effective treatment?

The available research does not provide any data on CRT Optimization for Heart Failure. Instead, it focuses on treatments for castration-resistant prostate cancer, which is unrelated to heart failure. ^{1 2 3 4 5}

Is cardiac resynchronization therapy (CRT) safe for humans?

Cardiac resynchronization therapy (CRT), including CRT-P and CRT-D, is generally considered safe for humans, as it is widely used to manage chronic heart failure. However, like any medical procedure, it may have risks, and the choice between different types of CRT devices should be made carefully based on individual patient needs. ^{6 7 8 9 10}

How is CRT optimization for heart failure different from other treatments?

CRT optimization is unique because it involves tailoring the settings of a cardiac resynchronization therapy device to improve heart function by synchronizing the heart's ventricles. This personalized approach aims to maximize the benefits of CRT, such as reducing hospitalizations and improving quality of life, by adjusting the device settings to each patient's specific needs. ^{10 11 12 13 14}

Research Team

Alan J Bank, MD

Principal Investigator

Allina Heath System

Eligibility Criteria

This trial is for adults over 18 with heart failure who have a CRT device but haven't seen much improvement. They should be on standard therapy, have had the device for more than 4 months, and show suboptimal heart rhythm patterns on an ECG. People can't join if they're in acute heart failure, pregnant or breastfeeding, allergic to certain ECG or MRI materials, have specific types of pacing leads or irregular heartbeat issues.

Inclusion Criteria

Your heart's electrical signals are not working well with the current settings of the device.

I am currently receiving standard treatment for my condition.

My heart's pumping ability hasn't improved much or remains low after treatment.

Exclusion Criteria

You have a heart condition with frequent abnormal heartbeats.

My heart is unable to pump blood effectively.

Patient is enrolled in concurrent research study that would potentially confound the results of this study (noting: co-enrollment acceptable if patient is enrolled in registry study)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Baseline CMR study to assess acute effects of CRT optimization on mechanical synchrony, LV regional wall motion, and LV structure/function

During Baseline Assessment

Treatment

Randomized treatment with either baseline CRT programming or electrocardiography-guided optimal CRT programming

6 months

Crossover Treatment

Active comparator group crosses over to experimental group for CRT device programming to optimal settings

6 months

Follow-up

Follow-up CMR and echocardiogram to assess chronic effects of CRT optimization

12 months

Treatment Details

Interventions

• Programming of CRT device settings

Trial Overview The study tests how adjusting the settings of a CRT device might help patients who don't respond well to initial treatment. It uses cardiac MR imaging to see the effects of these adjustments both right away and over time.

Participant Groups

Group I: Electrocardiography-guided optimal CRT programming Experimental Treatment 1 Intervention

The experimental arm patients will have CRT device programmed based on the electrocardiographic assessment for 12 months.

Group II: Baseline CRT programming Active Control 1 Intervention

The comparator arm patients will remain at baseline CRT programming for the first 6 months, and then will crossover to the experimental arm and CRT device will be programmed to optimal settings derived from the electrocardiographic assessment for the following 6 months.

Programming of CRT device settings is already approved in United States, European Union, Canada for the following indications:

Approved in United States as CRT-D for:

• Moderate to severe heart failure (NYHA Class III-IV)
• Mild heart failure (NYHA Class II) with Left Bundle Branch Block (LBBB)
• Asymptomatic heart failure (NYHA Class I) with LBBB

Approved in European Union as CRT-D for:

• Moderate to severe heart failure (NYHA Class III-IV)
• Mild heart failure (NYHA Class II)

Approved in Canada as CRT-D for:

• Moderate to severe heart failure (NYHA Class III-IV)
• Mild heart failure (NYHA Class II)

Who Is Running the Clinical Trial?

Allina Health System

Lead Sponsor

Trials

60

Recruited

1,178,000+

Minneapolis Heart Institute Foundation

Collaborator

Trials

32

Recruited

15,700+

Findings from Research

Androgen depletion therapy (ADT) is effective for treating prostate cancer, but many patients develop castration-resistant prostate cancer (CRPC) within a few years, highlighting the need for new treatment options.

At the 2012 ASCO Meeting, promising results were presented from two global randomized trials testing new agents, abiraterone acetate and MDV3100, specifically targeting CRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Epoch making development of new drugs for prostate cancer]. Akaza, H.[2013]

In a study of 69 patients with castration-resistant prostate cancer (CRPC), the sequence of treatment using abiraterone followed by enzalutamide (A-E) resulted in better progression-free survival (PFS) compared to the reverse sequence (E-A), indicating that treatment order may impact effectiveness.

Pretreatment levels of lactate dehydrogenase (LDH) and hemoglobin were identified as significant predictors of longer combined PFS and overall survival (OS), suggesting that these factors could help guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lactate dehydrogenase predicts combined progression-free survival after sequential therapy with abiraterone and enzalutamide for patients with castration-resistant prostate cancer. Mori, K., Kimura, T., Onuma, H., et al.[2021]

In a multicenter study involving 86 patients with oligoprogressive castration-resistant prostate cancer, stereotactic body radiation therapy (SBRT) showed a median new metastasis-free survival of 12.3 months, indicating its potential effectiveness in managing this condition.

The study also found that 72.1% of patients were free from systemic treatment one year after SBRT, suggesting that this treatment can delay the need for further systemic therapies in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metastasis-directed stereotactic radiotherapy for oligoprogressive castration-resistant prostate cancer: a multicenter study. Triggiani, L., Mazzola, R., Magrini, SM., et al.[2020]

The Prostate Cancer Radiographic Assessments for Detection of Advanced Recurrence II Working Group recommends a layered treatment approach for managing metastatic castration-resistant prostate cancer (CRPC), utilizing therapies with unique or complementary mechanisms of action.

This consensus was formed due to the lack of large-scale clinical trials, emphasizing the importance of individualized treatment strategies based on available data and clinical experience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Therapeutic Layering in Optimizing Treatment for Patients With Castration-resistant Prostate Cancer (Prostate Cancer Radiographic Assessments for Detection of Advanced Recurrence II). Crawford, ED., Petrylak, DP., Shore, N., et al.[2022]

A panel of 18 Spanish experts developed standardized recommendations for managing castration-resistant prostate cancer (CRPC), emphasizing the importance of using advanced imaging techniques like whole-body MRI for better detection of metastases, despite their higher costs.

For patients with M0 CRPC, no drug treatment is recommended, while M1 CRPC patients should primarily receive enzalutamide or abiraterone, and/or docetaxel based on their symptoms, to improve their quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Consensus on castration-resistant prostate cancer management in Spain.] Alcaraz, A., Martínez-Piñeiro, L., Rodríguez, A., et al.[2018]

In a study of 60 patients with chronic heart failure, those who received implantable cardioverter defibrillator/cardiac resynchronization therapy defibrillator (ICD/CRT-D) showed a significantly lower readmission rate for heart failure (30.0%) compared to the control group (56.67%), indicating improved management of heart failure with remote monitoring.

The ICD/CRT-D group also experienced a much faster diagnosis time for ventricular tachycardia/ventricular events (2.55 days) compared to the control group (37.32 days), allowing for quicker medical intervention and potentially better patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of ICD/CRT-D Implantation on Adverse Events and Readmission Rate in Patients with Chronic Heart Failure (CHF). Liu, P., Xing, L.[2023]

Cardiac resynchronization therapy with a pacemaker (CRT-P) is a valid treatment option for chronic heart failure, and there is no strong evidence that all patients need a biventricular implantable cardioverter-defibrillator (CRT-D), which is more complex and costly.

For patients showing significant heart improvement without dangerous heart rhythms, it may be reasonable to switch from CRT-D to CRT-P when the device's battery runs low, suggesting a more tailored approach to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Why We Have to Use Cardiac Resynchronization Therapy-Pacemaker More. Daubert, JC., Martins, R., Leclercq, C.[2018]

The use of cardiac resynchronization therapy (CRT) devices, including CRT-P and CRT-D, has significantly increased due to better operator experience and expanded patient eligibility.

In a specific case, innovative device programming successfully achieved effective biventricular pacing despite challenges with repeated dislodgement of the atrial lead, highlighting advancements in CRT technology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of a novel pacing mode to achieve biventricular pacing in a patient with recurrent atrial lead dislodgement after CRT-D implantation. Devidutta, S., Sridevi, C., Narasimhan, C.[2020]

In a study of 84 heart failure patients with biventricular pacemakers (CRT-P), 13.1% experienced unsustained ventricular tachyarrhythmias during an average follow-up of 29 months, indicating that while CRT-P can be tolerated, there is still a risk of arrhythmias.

The upgrade to a CRT-D (with a defibrillator) did not significantly prevent sudden death, as evidenced by one patient who died suddenly 15 months after the upgrade, suggesting that CRT-P may be a viable option for certain patients without an ICD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of ventricular arrhythmias in patients with cardiac resynchronization therapy without back-up ICD: a single-center experience. Bortnik, M., Degiovanni, A., Dell'era, G., et al.[2014]

In a study of 170 chronic heart failure patients undergoing cardiac resynchronization therapy (CRT), many had suboptimal device settings at their first follow-up, highlighting the need for careful adjustment to improve patient outcomes.

True biventricular pacing was achieved in only 44% of patients, and significant adjustments were often needed for atrioventricular (AV) delays, indicating that expert follow-up is crucial for optimizing CRT effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive cardiac resynchronization therapy optimization in the real world. Steffel, J., Rempel, H., Breitenstein, A., et al.[2016]

Cardiac resynchronization therapy (CRT) can be more effective when the pacing is individually tailored to address mechanical delays in ventricular contractions, rather than using standard simultaneous biventricular pacing.

Optimizing device programming, including adjusting atrial to ventricular timing and right to left ventricular pacing delays, can significantly enhance heart function and improve patient outcomes in CRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimization of cardiac resynchronization therapy after implantation. Hasan, A., Abraham, WT.[2021]

Cardiac resynchronization therapy (CRT) significantly improves heart function, reduces hospitalizations, and enhances quality of life for selected heart failure patients by synchronizing ventricular contractions.

To maximize the benefits of CRT, it is essential to tailor the therapy to each patient through optimal programming of the device, as heart failure patients have diverse needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal programming in cardiac resynchronization therapy. Ermiş, C.[2007]

Cardiac resynchronization therapy (CRT) significantly improves quality of life and reduces hospitalizations for heart failure in patients with reduced ejection fraction and electrical dyssynchrony, particularly those with left bundle branch block and a QRS duration of 150 ms or more.

To maximize the benefits of CRT, careful patient selection, optimal lead placement, and thorough multidisciplinary care, including medication management and patient education, are essential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CRT Optimization: What Is New? What Is Necessary? Dauw, J., Martens, P., Mullens, W.[2020]

Cardiac resynchronization therapy (CRT) using biventricular pacing is effective for heart failure patients, improving symptoms, left ventricular function, hospitalization rates, and survival, particularly in those with reduced LV function and a widened QRS complex.

To enhance the effectiveness of CRT and minimize non-response, it is crucial to implant the LV lead at the optimal site, avoiding myocardial scar, and to carefully program the device for optimal atrioventricular and interventricular intervals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac resynchronization therapy: Dire need for targeted left ventricular lead placement and optimal device programming. Pastromas, S., Manolis, AS.[2020]

References

1. Japan pubmed.ncbi.nlm.nih.gov

[Epoch making development of new drugs for prostate cancer]. [2013]

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

Lactate dehydrogenase predicts combined progression-free survival after sequential therapy with abiraterone and enzalutamide for patients with castration-resistant prostate cancer. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

Metastasis-directed stereotactic radiotherapy for oligoprogressive castration-resistant prostate cancer: a multicenter study. [2020]

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

The Role of Therapeutic Layering in Optimizing Treatment for Patients With Castration-resistant Prostate Cancer (Prostate Cancer Radiographic Assessments for Detection of Advanced Recurrence II). [2022]

5. Spain pubmed.ncbi.nlm.nih.gov

[Consensus on castration-resistant prostate cancer management in Spain.] [2018]

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

Effect of ICD/CRT-D Implantation on Adverse Events and Readmission Rate in Patients with Chronic Heart Failure (CHF). [2023]

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

Why We Have to Use Cardiac Resynchronization Therapy-Pacemaker More. [2018]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Use of a novel pacing mode to achieve biventricular pacing in a patient with recurrent atrial lead dislodgement after CRT-D implantation. [2020]

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

Prevalence of ventricular arrhythmias in patients with cardiac resynchronization therapy without back-up ICD: a single-center experience. [2014]

10. Poland pubmed.ncbi.nlm.nih.gov

Comprehensive cardiac resynchronization therapy optimization in the real world. [2016]

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

Optimization of cardiac resynchronization therapy after implantation. [2021]

12. Turkey pubmed.ncbi.nlm.nih.gov

Optimal programming in cardiac resynchronization therapy. [2007]

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

CRT Optimization: What Is New? What Is Necessary? [2020]

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

Cardiac resynchronization therapy: Dire need for targeted left ventricular lead placement and optimal device programming. [2020]