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

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

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.

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).