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

NCT05973591 | Unknown

• 1 other identifier: 4-2022-1665
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

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.

Conditions

Dilated Cardiomyopathy; Ventricular Remodeling; Heart Failure, Reduced Ejection Fraction

Outcome Measures

Primary Outcomes (1)

• Prevalence of of LVRR in patients with NIDCM

  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).

  at 12 months after the initiation of GDMT

Secondary Outcomes (7)

• Prevalence of LVRR in NIDCM at 8 months after initiation of GDMT

  at 8 months after GDMT initiation

• Extent of LVRR (measured by LVEDD/LVESD, LAVI, E/e' in echocardiography) in NIDCM at 8 and 12 months after GDMT initiation

  at 8 and 12 months after GDMT initiation

• Clinical course of LVRR in NIDCM

  at 8 and 12 months after GDMT initiation

• Effect of targeted HR (HF <60 or 70/min) on LVRR in NIDCM at 8 and 12 months after GDMT initiation

  at 8 and 12 months after GDMT initiation

• Effect of degree of change in HR before and after GDMT on LVRR in NIDCM at 8 and 12 months after GDMT initiation

  at 8 and 12 months after GDMT initiation

Study Arms (4)

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\*\*

Eligibility Criteria

• Age: 19 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients diagnosed with NIDCM with sinus rhythm

You may qualify if:

• 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
• Sinus rhythm
• Baseline LVEF of 40% or less (LVEF≤40%)
• Patients containing baseline heart rate (HR)
• In the Ivabradine group, baseline HR must be \>75 bpm at the time of ivabradine dosing.

You may not qualify if:

• 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)
• Heart failure with other etiologies (e.g., valvular heart disease, endocrine disease).
• Previous recovery history of left ventricular systolic function (LVEF)
• Cardiac resynchronization therapy (CRT) implantation
• Persistent/permanent atrial fibrillation
• \) 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).

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Severance hospital

Seoul, South Korea

Location

MeSH Terms

Conditions

Cardiomyopathy, Dilated; Ventricular Remodeling; Heart Failure, Systolic

Condition Hierarchy (Ancestors)

Cardiomegaly; Heart Diseases; Cardiovascular Diseases; Cardiomyopathies; Laminopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Heart Failure

Study Officials

• Seok-Min Kang

  Division of Cardiology, Yonsei Cardiovascular Hospital, Yonsei University College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2023
• First Posted: August 3, 2023
• Study Start: July 15, 2023
• Primary Completion: June 1, 2024
• Study Completion: December 31, 2024
• Last Updated: August 3, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)