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High Dose β-Blocker Therapy Triggers Additional Reverse Remodeling in Patients With Idiopathic Non-Ischemic
Daisuke Nitta1, Koichiro Kinugawa, Teruhiko Imamura
1Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo.
Insights
High-dose carvedilol (40 mg/day) significantly improved left ventricular ejection fraction (LVEF) and reduced dimensions in heart failure patients. This dose effectively induced left ventricular reverse remodeling (LVRR) in a majority of patients.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Carvedilol improves outcomes and promotes left ventricular reverse remodeling (LVRR) in heart failure with reduced left ventricular ejection fraction (LVEF).
- Dose-dependency of carvedilol is recognized, but data on high-dose effects in Japan are limited.
Purpose of the Study:
- To evaluate the efficacy of high-dose carvedilol (40 mg/day) in patients with idiopathic non-ischemic cardiomyopathy who did not achieve LVRR on standard doses.
- To identify predictors of LVRR in response to high-dose carvedilol therapy.
Main Methods:
- Enrolled 23 patients with idiopathic non-ischemic cardiomyopathy and LVEF ≤ 45% despite > 3 months of carvedilol 20 mg/day.
- Assessed changes in LVEF, LV end-diastolic diameter (LVDd), and LV end-systolic diameter (LVDs) after switching to carvedilol 40 mg/day for > 3 months.
- Defined LVRR based on final LVEF and/or improvement in LVEF and LV dimensions.
Main Results:
- High-dose carvedilol significantly improved LVEF (+9.1%, P=0.002) and reduced LVDd (-4.6 mm) and LVDs (-6.9 mm).
- 17 out of 23 patients achieved LVRR.
- Changes in log B-type natriuretic peptide (BNP), LVDd, and LVDs at the 20 mg dose predicted response to high-dose therapy.
Conclusions:
- High-dose carvedilol (40 mg/day) effectively induced additional LVRR in Japanese patients with idiopathic non-ischemic cardiomyopathy.
- Early changes in BNP, LVDd, and LVDs during standard carvedilol therapy may predict response to dose escalation.
Abstract:
Carvedilol has established its evidence to improve prognosis and facilitate left ventricular reverse remodeling (LVRR) in heart failure patients with reduced left ventricular ejection fraction (LVEF), and many studies have supported its dose-dependency. However, there are few studies demonstrating the effect of high dose carvedilol in Japan. We enrolled 23 patients with idiopathic non-ischemic cardiomyopathy, in whom LVEF remained 45% or less despite 20 mg/ day of carvedilol therapy for > 3 months. After high dose (40 mg/day) carvedilol therapy for > 3 months, LVEF improved (+9.1%, P = 0.002), and LV end-diastolic diameter (LVDd) and LV end-systolic diameter (LVDs) reduced (-4.6 and -6.9 mm, respectively, P < 0.05) compared with the baseline data. Finally, 17 patients achieved LVRR after the high dose, when LVRR was defined as 1) those with final EF > 45%, and 2) those with final EF < 45% but who attained increases in LVEF > 10%, or LVEF > 5% with a decrease in LV end-diastolic dimension index (LVDDI) > 5%. Baseline predictors for LVRR after high dose carvedilol were the change rates of log B-type natriuretic peptide (BNP), LVDd, and LVDs from the time of pre-carvedilol introduction to enrollment (P < 0.05, respectively). In conclusion, high dose carvedilol triggered additional LVRR in patients with idiopathic non-ischemic cardiomyopathy and the change rates of log BNP, LVDd, and LVDs at 20 mg carvedilol may be predictors for the additional LVRR at high dose.
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