The Impact of Ivabradine on Left Ventricular Reverse Remodeling in Nonischemic Dilated Cardiomyopathy (NIDCM) on Current Medical Therapy Era

• ClinicalTrials.gov Identifier: NCT05973591
• Recruitment Status: Active, not recruiting
• First Posted: August 3, 2023
• Last Update Posted: August 3, 2023
• Sponsor: Yonsei University
• Information provided by (Responsible Party): Yonsei University

Study Description

Brief Summary:

In non-ischemic dilated cardiomyopathy (NIDCM), left ventricular reverse remodeling (LVRR) can be achieved through guideline-directed medical therapy (GDMT). LVRR is defined as an increase in left ventricular ejection fraction (LVEF) of more than 10% in heart failure patients with a baseline LVEF of 40% or less, or an increase in LVEF of more than 40% at follow-up, which is classified as heart failure with improved EF (HFimpEF) according to current guidelines. Several studies have examined the prevalence and predictors of LVRR in NIDCM. However, there is a lack of research on LVRR in the context of contemporary pharmacotherapy. Studies have demonstrated the beneficial effects of ivabradine in heart failure with reduced ejection fraction (HFrEF), improving patients' prognosis. A sub-study of the SHIFT trial indicated that ivabradine may also contribute to cardiac remodeling reversal in patients with HFrEF. However, there is limited evidence exploring the relationship between ivabradine and LVRR, particularly in the context of NIDCM.

Consequently, this study is a retrospective, multi-center cohort study aiming to evaluate the impact of ivabradine on LVRR in patients with NIDCM in the current era of medical therapy. Furthermore, by conducting this study, we aim to gain insights into the potential role of ivabradine in promoting LVRR in NIDCM patients receiving contemporary drug therapy.

Condition or disease
Dilated Cardiomyopathy; Ventricular Remodeling; Heart Failure, Reduced Ejection Fraction

Study Design

• Study Type: Observational
• Estimated Enrollment: 500 participants
• Observational Model: Cohort
• Time Perspective: Retrospective
• Official Title: The Impact of Ivabradine on Left Ventricular Reverse Remodeling in Nonischemic Dilated Cardiomyopathy (NIDCM) on Current Medical Therapy Era
• Actual Study Start Date: July 15, 2023
• Estimated Primary Completion Date: June 2024
• Estimated Study Completion Date: December 31, 2024

Groups and Cohorts

Group/Cohort
achieved HR ≥ 70 bpm without ivabradine; **Achieved HR : heart rate (HR) at 12 month follow up after the initiation of GDMT**
achieved HR < 70 bpm without ivabradine; **Achieved HR : heart rate (HR) at 12 month follow up after the initiation of GDMT**
achieved HR ≥ 70 bpm with ivabradine; **Achieved HR : heart rate (HR) at 12 month follow up after the initiation of GDMT**
achieved HR < 70 bpm with ivabradine; **Achieved HR : heart rate (HR) at 12 month follow up after the initiation of GDMT**

Outcome Measures

Primary Outcome Measures :

1. Prevalence of of LVRR in patients with NIDCM [ Time Frame: at 12 months after the initiation of GDMT ]
   LVRR is characterized by an increase in left ventricular ejection fraction (LVEF) of more than 10% in heart failure patients with a baseline LVEF of 40% or less, or an increase in LVEF of more than 40% during follow-up, which is classified as heart failure with improved EF (HFimpEF). Furthermore, the initiation of guideline-directed medical therapy (GDMT) is defined as the timeframe for commencing treatment with an angiotensin-converting enzyme inhibitor (ACEi), angiotensin II receptor antagonist (ARB), or beta-blocker after the diagnosis of heart failure with reduced ejection fraction (HFrEF).

Secondary Outcome Measures :

1. Prevalence of LVRR in NIDCM at 8 months after initiation of GDMT [ Time Frame: at 8 months after GDMT initiation ]
2. Extent of LVRR (measured by LVEDD/LVESD, LAVI, E/e' in echocardiography) in NIDCM at 8 and 12 months after GDMT initiation [ Time Frame: at 8 and 12 months after GDMT initiation ]
3. Clinical course of LVRR in NIDCM [ Time Frame: at 8 and 12 months after GDMT initiation ]
4. Effect of targeted HR (HF <60 or 70/min) on LVRR in NIDCM at 8 and 12 months after GDMT initiation [ Time Frame: at 8 and 12 months after GDMT initiation ]
5. Effect of degree of change in HR before and after GDMT on LVRR in NIDCM at 8 and 12 months after GDMT initiation [ Time Frame: at 8 and 12 months after GDMT initiation ]
6. Impact of GDMT on LVRR in NIDCM at 8 and 12 months after GDMT initiation [ Time Frame: at 8 and 12 months after GDMT initiation ]
7. Prevalence of symptomatic bradycardia, syncope, or any other adverse events with Ivabradine [ Time Frame: at 8 and 12 months after GDMT initiation ]

Eligibility Criteria

• Ages Eligible for Study: 19 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

Patients diagnosed with NIDCM with sinus rhythm

Criteria

Inclusion Criteria:

1. Diagnosed with non-ischemic dilated cardiomyopathy (NIDCM) by performing coronary artery imaging (coronary angiography, CT angiography, or SPECT scan) at the time of diagnosis of HFrEF
2. Sinus rhythm
3. Baseline LVEF of 40% or less (LVEF≤40%)

4. Patients containing baseline heart rate (HR)

   • In the Ivabradine group, baseline HR must be >75 bpm at the time of ivabradine dosing.

Exclusion Criteria:

1. Patients with confirmed ischemic cardiomyopathy (when stenosis of 75% or more of major coronary arteries is confirmed on coronary artery imaging or ischemic cardiomyopathy findings such as transmural LGE on cardiac MRI)
2. Heart failure with other etiologies (e.g., valvular heart disease, endocrine disease).
3. Previous recovery history of left ventricular systolic function (LVEF)
4. Cardiac resynchronization therapy (CRT) implantation
5. Persistent/permanent atrial fibrillation

7) Contraindication to the administration of ivabradine according to the Summary of Product Characteristics (SmPC)

• Hypersensitivity reactions
• Symptomatic bradycardia or resting heart rate < 75 bpm prior to treatment
• Cardiogenic shock, acute myocardial infarction, severe hypotension (< 90/50 mmHg), severe hepatic failure, sinus syndrome, atrial block, unstable or acute heart failure, pacemaker dependence (with pacing dominance), unstable angina, third degree atrioventricular block
• Cytochrome P450 3A4 inhibitors: Azole class antifungals (ketoconazole,itraconazole), Macrolide class antibiotics (clarithromycin, erythromycin per os, josamycin, telithromycin), HIV protease inhibitors (nelfinavir, ritonavir), nefazodone or any concomitant use with verapamil or diltiazem (moderate CYP3A4 inhibitors with heart rate reducing properties).

Contacts and Locations

Locations

Korea, Republic of

Severance hospital

Seoul, Korea, Republic of

Sponsors and Collaborators

Yonsei University

Investigators

• Principal Investigator: Seok-Min Kang; Division of Cardiology, Yonsei Cardiovascular Hospital, Yonsei University College of Medicine

More Information

• Responsible Party: Yonsei University
• ClinicalTrials.gov Identifier: NCT05973591
• Other Study ID Numbers: 4-2022-1665
• First Posted: August 3, 2023
• Last Update Posted: August 3, 2023
• Last Verified: July 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Cardiomyopathies; Cardiomyopathy, Dilated; Heart Failure, Systolic; Ventricular Remodeling; Heart Failure; Heart Diseases; Cardiovascular Diseases; Cardiomegaly; Laminopathies; Genetic Diseases, Inborn; Pathological Conditions, Anatomical