Clinical trial NCT05973591: The Impact of Ivabradine on Left Ventricular Reverse Remodeling in Nonischemic Dilated Cardiomyopathy (NIDCM) on Current Medical Therapy Era
Official title: The Impact of Ivabradine on Left Ventricular Reverse Remodeling in Nonischemic Dilated Cardiomyopathy (NIDCM) on Current Medical Therapy Era
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Dilated Cardiomyopathy
Ventricular Remodeling
Heart Failure, Reduced Ejection Fraction
Lead sponsor: Yonsei University
Sponsor class: OTHER
First posted: 2023-08-03
Enrollment: 500
Sex: ALL
Minimum age (years): 19
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients diagnosed with NIDCM with sinus rhythm

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.


Eligibility 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).

Primary outcomes:
measure: Prevalence of of LVRR in patients with NIDCM
timeFrame: at 12 months after the initiation of GDMT
Secondary outcomes:
measure: Prevalence of LVRR in NIDCM at 8 months after initiation of GDMT
timeFrame: at 8 months after GDMT initiation
measure: Extent of LVRR (measured by LVEDD/LVESD, LAVI, E/e' in echocardiography) in NIDCM at 8 and 12 months after GDMT initiation
timeFrame: at 8 and 12 months after GDMT initiation
measure: Clinical course of LVRR in NIDCM
timeFrame: at 8 and 12 months after GDMT initiation
measure: Effect of targeted HR (HF <60 or 70/min) on LVRR in NIDCM at 8 and 12 months after GDMT initiation
timeFrame: at 8 and 12 months after GDMT initiation
measure: Effect of degree of change in HR before and after GDMT on LVRR in NIDCM at 8 and 12 months after GDMT initiation
timeFrame: at 8 and 12 months after GDMT initiation
measure: Impact of GDMT on LVRR in NIDCM at 8 and 12 months after GDMT initiation
timeFrame: at 8 and 12 months after GDMT initiation
measure: Prevalence of symptomatic bradycardia, syncope, or any other adverse events with Ivabradine
timeFrame: at 8 and 12 months after GDMT initiation
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Severance hospital
Study officials:
affiliation: Division of Cardiology, Yonsei Cardiovascular Hospital, Yonsei University College of Medicine
name: Seok-Min Kang
role: PRINCIPAL_INVESTIGATOR
References: