Researchers from the Medical University of Vienna have identified promising advancements pertaining to Duchenne muscular dystrophy (DMD), particularly concerning heart function. A new study published on March 15, 2025, revealed how chronic administration of ivabradine (IVA), previously authorized for heart failure treatment, significantly improves cardiac calcium handling and function.
DMD is characterized by severe muscle degeneration and associated cardiac complications, primarily due to mutations affecting dystrophin, which plays a key role in muscle integrity. One of the chief concerns for patients is the resultant decline in heart function, particularly due to impaired calcium handling within the cardiovascular system. This impairment leads to arrhythmias and reduced contractile capacity, creating dire health complications for affected individuals.
The innovative study utilized the dystrophin-deficient DMDmdx rat model to explore the effects of long-term IVA treatment on cardiac function. The hypothesis centered on the premise: chronic IVA administration would improve calcium handling properties within dystrophic ventricular cardiomyocytes – the heart's muscle cells – and thereby augment heart contractile performance.
Administration of IVA occurred via drinking water at a dosage of 10 mg/kg/day for four months, beginning at 5 months of age. Following this protocol, researchers conducted detailed analyses on the resultant impacts on cardiac function. According to the findings, IVA treatment significantly improved calcium handling properties across dystrophic cardiomyocytes.
More precisely, results indicated enhanced electrically-evoked calcium transients and accelerated decay rates following IVA treatment. This suggests not only improved calcium release from the sarcoplasmic reticulum – the organelle storing calcium necessary for muscle contraction – but also demonstrates a swifter removal of calcium post-contraction, optimizing cardiac performance.
Transthoracic echocardiography results provided quantifiable evidence of IVA’s effectiveness. The enhancement reflected improved left ventricular ejection fraction (LVEF) and fractional shortening, two key metrics signifying heart contractility. Elevated LVEF percentages correlate with stronger heart contractions, effectively increasing blood flow throughout the body, particularly beneficial for DMD patients.
Despite these promising findings, the researchers noted important insights concerning cardiac health sustained post-treatment. While ivabradine enhanced levels of cardiac function metrics such as LVEF, factors including cardiac fibrosis and apoptosis, indicative of heart tissue damage, were not significantly reduced by the drug. This delineates the need for comprehensive therapies tackling multiple facets of cardiac degeneration.
Interestingly, the study also highlighted findings surrounding vascular function. Chronic IVA treatment did not markedly improve endothelium-dependent vasorelaxation, raising questions about its full spectrum of benefits addressing overall cardiovascular function.
On the molecular level, the research examined the expression of calcium-handling proteins such as SERCA2 and phospholamban. While SERCA2 levels significantly reduced in dystrophic rats compared to their wild-type counterparts, ivabradine treatment did not affect SERCA2 expression levels, steering the investigation toward alternative mechanisms for calcium enhancement observed with IVA. This finding indicates possible dissociation between clinical benefits and changes at the protein expression level.
The overall conclusion drawn from the research suggests chronic IVA administration can be favorable not only for improving calcium handling but also for addressing contractile dysfunction associated with dystrophin deficiency. “Chronic IVA administration enhanced contractile function in the dystrophic heart by improvement of Ca handling in ventricular cardiomyocytes,” wrote the authors of the article. Importantly, they indicated, “Long-term IVA administration may be beneficial for DMD patients.”
These breakthroughs offer optimism around pharmacotherapeutic strategies addressing cardiac health challenges faced by DMD patients. Subsequent studies will be necessary to explore the full breadth of therapeutic potentials offered by ivabradine, particularly exploring the dynamics of calcium handling and the disparities between treatment effects on heart functionality versus tissue health.
Further research should evaluate the interaction of IVA with calcium regulatory mechanisms, potentially paving the way toward augmenting clinical strategies for managing cardiac health complications stemming from Duchenne muscular dystrophy.
The hope remains to translate such findings to human treatments, thereby enhancing the quality of life for those afflicted by DMD and similar muscle degenerative conditions.