CRT Optimization for Heart Failure

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to improve the settings of a heart device called a CRT (Cardiac Resynchronization Therapy), which assists people with heart failure who haven't benefited from the device yet. Researchers seek to determine if adjusting the CRT device using information from standard heart tests (such as ECGs) can enhance its effectiveness. Participants must have had a CRT device in place for over four months without significant improvement in heart function. The trial involves two groups: one will maintain their regular settings for a period before switching to optimized settings, while the other will start with the optimized settings immediately. This trial suits those who have a CRT device but continue to experience symptoms. As an unphased trial, it offers a unique opportunity to potentially enhance the heart device's effectiveness through personalized adjustments.

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 prior data suggests that this CRT device programming is safe for heart failure patients?

Research has shown that cardiac resynchronization therapy (CRT) is generally safe for people with heart failure. CRT, a type of device therapy, has received FDA approval, indicating it has passed safety tests for use in other conditions. Early studies found that adjusting CRT device settings can improve heart function and quality of life.

Patients with CRT devices have experienced improvements without major safety issues. Specifically, reprogramming the CRT device has enhanced heart function and reduced heart size, which are positive outcomes. These changes did not increase deaths or hospital visits, indicating safety.

In this study, the treatment involves adjusting the CRT device based on heart activity readings (electrocardiographic assessment). This approach aims to optimize CRT for those who haven't responded well to the usual settings. While this adjustment is new, the basic CRT technology has a strong safety record. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores optimizing cardiac resynchronization therapy (CRT) device settings for heart failure patients using electrocardiographic assessments. Unlike standard CRT programming, which remains static, this approach adjusts the device settings based on detailed heart rhythm readings to potentially improve heart function. By tailoring the device settings to the individual's specific heart patterns, this method aims to enhance the effectiveness of CRT and improve patient outcomes.

What evidence suggests that optimizing CRT device programming is effective for heart failure?

Research has shown that cardiac resynchronization therapy (CRT) can significantly aid people with heart failure by enhancing heart function and reducing hospital visits. Studies have found that CRT improves heart pumping and quality of life for many heart failure patients. However, about 30% of patients do not benefit from CRT. This trial will compare two approaches: one group will remain at baseline CRT programming for the first 6 months, while the other group will have their CRT device programmed based on electrocardiographic (ECG) assessment for 12 months. Recent findings suggest that using ECG to guide CRT device programming could help patients who do not initially benefit from CRT. By adjusting device settings based on heart activity measurements, these patients might experience better heart function and fewer symptoms. ^{1 2 3 6 7}

Who Is on the Research Team?

Alan J Bank, MD

Principal Investigator

Allina Heath System

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

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]

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]

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]

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]

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]

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]

Citations

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Progress in Cardiac Resynchronisation Therapy and ... Cardiac resynchronization therapy via left bundle branch pacing vs. optimized biventricular pacing with adaptive algorithm in heart failure ...

2. heartrhythmjournal.com heartrhythmjournal.com/article/S1547-5271(24)00198-X/fulltext

Personalized cardiac resynchronization therapy guided by ... Biventricular pacing (BVP) was confirmed to improve left ventricular ejection fraction (LVEF) and reduce heart failure hospitalization and ...

3. jacc.org jacc.org/doi/10.1016/j.jacep.2020.11.029

His-Optimized Cardiac Resynchronization Therapy With ... Cardiac resynchronization therapy (CRT) has been the mainstay for treatment of heart failure (HF) in patients with reduced left ventricular ejection fraction ( ...

4. tandfonline.com tandfonline.com/doi/full/10.1080/14779072.2024.2445246

Optimizing outcomes from cardiac resynchronization therapy Cardiac Resynchronization Therapy (CRT) is an effective treatment for heart failure (HF) in approximately two-thirds of recipients, with a third remaining ...

5. ahajournals.org ahajournals.org/doi/10.1161/JAHA.118.009559

Twelve‐Lead ECG Optimization of Cardiac ... Randomized controlled clinical trials have demonstrated that CRT results in improved heart failure symptoms, functional status, exercise ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7067690/

Optimization of Chronic Cardiac Resynchronization ... CRT reprogramming to maximize biventricular fusion pacing significantly increased LVEF and reduced LVESV in patients with chronic CRT devices.

7. sciencedirect.com sciencedirect.com/science/article/pii/S2666501823002209

Clinical outcomes of automatic algorithms in cardiac ... Automatic algorithms that change AV or VV intervals did not improve mortality, heart failure hospitalizations, or cardiovascular symptoms in patients with ...