Heart failure & cardiomyopathies
Heart Rate Reduction Is Associated With Reverse Left Ventricular Remodeling and Mechanism-Specific Molecular Phenotypes in Dilated Cardiomyopathy
Authors' conclusion
In patients with nonischemic dilated cardiomyopathy in sinus rhythm, HR lowering per se (1) is associated with substantial left ventricular reverse remodeling; (2) its absence can cause β-blocker reverse remodeling nonresponse; and (3) when from HCN4 channel inhibition, results in a unique molecular phenotype.
Study context
- Population
- Patients with nonischemic dilated cardiomyopathy in sinus rhythm and refractory to β-blockade for both HR lowering and reverse remodelingrandomized 2:1 to ivabradine or placebo
- Participants
- 22 patients
- Comparison
- Decreased versus Unchanged HR groups
- Decreased HRn = 90
- Unchanged HRn = 8
Methodological detailsplacebo, 24 weeks treatment while maintaining target doses of β-blockers, primary statistical analysis between HR change categories divided at the median
- Placebo
- 24 weeks treatment while maintaining target doses of β-blockers
- Primary statistical analysis between HR change categories divided at the median
Primary result
As reported in the abstract
HR · baseline and 24 weeks
| Group | Value | P |
|---|---|---|
| Decreased HR | 82.9±6.8 and 69.7±8.0 beats per minute | P =0.0005 |
| Unchanged HR | 80.8±5.7 and 79.2±11.6 beats per minute | P =0.58 |
Value
Decreased HR82.9±6.8 and 69.7±8.0 beats per minute
Unchanged HR80.8±5.7 and 79.2±11.6 beats per minute
P
Decreased HRP =0.0005
Unchanged HRP =0.58
Further findings
| Outcome | Decreased HR | Unchanged HR |
|---|---|---|
| LVEF · baseline and 24 weeks | 29.4±8.8% to 44.2±9.4% | 26.6±11.4% and 29.2±12.0% |
| P | P =0.0003 | P =0.28 |
Treatment received
- Unchanged HR: received ivabradine
- 3
- Unchanged HR: received placebo
- 5
- All completing Decreased HR subjects were treated with ivabradine
HR and left ventricular ejection fraction (LVEF) changes vs previous β-blocker study
- HR and LVEF changes were not different from a previously conducted β-blocker nonischemic dilated cardiomyopathy study subdivided into LVEF responders and nonresponders
Differentially expressed genes
- Differentially expressed genes in the Decreased versus Unchanged HR groups
- 151
- Nonconcordant compared with β-blocker HR/LVEF responders versus nonresponders
- >99%
- Shared differentially expressed genes
- 2
- Multiple unique differentially expressed genes in Decreased HR including NRG1 upregulation are considered cardioprotective or involved in cardiac development
Original publication
Heart Rate Reduction Is Associated With Reverse Left Ventricular Remodeling and Mechanism-Specific Molecular Phenotypes in Dilated Cardiomyopathy. Circ Heart Fail. Published 7 March 2025. doi:10.
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