Heart with interwoven vessels, symbolizing systemic right ventricle, enveloped in protective light.

Systemic Right Ventricle: Can Valsartan Make a Difference?

Jordan Keane in Health & Wellness December 2025 • 4 min read.

"Exploring the impact of valsartan on heart health for patients with systemic right ventricles."

For individuals who have undergone an atrial switch procedure for complete transposition of the great arteries (TGA) or those with congenitally corrected transposition of the great arteries (ccTGA), the gradual decline of the systemic right ventricle (RV) poses a significant and unavoidable challenge. This decline is a primary contributor to both morbidity and mortality, underscoring the critical need for effective interventions.

Currently, the data available regarding the use of renin-angiotensin-aldosterone system (RAAS) inhibitors in this specific patient population is limited. The conclusions drawn from existing studies are often inconsistent, primarily due to the small number of patients involved. This scarcity of robust data highlights the necessity for further research to determine the true potential of these treatments.

The Valsartan in the Systemic Right Ventricle (VAL-SERVE) trial, we aimed to build on previous findings to investigate the long-term effects of valsartan on clinical outcomes in patients with systemic right ventricles. Our goal was to provide more definitive insights into how this medication can impact this vulnerable population, and to assess the longer-term effects of valsartan on clinical outcomes in patients enrolled in the VAL-SERVE trial

Valsartan and Systemic RV: What the Study Revealed

Heart with interwoven vessels, symbolizing systemic right ventricle, enveloped in protective light.

Between 2006 and 2009, a group of 88 adults was selected and divided randomly into two groups. One group received valsartan, and the other received a placebo. This treatment was administered consistently for three years. The researchers defined specific endpoints to measure the effectiveness of the treatments. These included overall survival and the absence of clinical events such as arrhythmia, heart failure, the necessity for tricuspid valve surgery, and death. These measures helped provide a clear picture of the treatment's impact on patient health.

Following the initial trial period, the use of cardiac medications and the duration of follow-up were similar across both groups, with an average of 8.3 years. During this extended observation, six patients died—three from the valsartan group and three from the placebo group. This indicated no significant difference in survival between the two treatments (P=0.999).

No significant differences were observed in either the combined or individual clinical endpoints between the groups. The long-term survival rates free from events were approximately 50% in the valsartan group and 34% in the placebo group.
However, in patients who were symptomatic, valsartan significantly decreased the risk of events compared to the placebo.
The benefits were noted only in symptomatic patients, suggesting that valsartan’s protective effects are more pronounced in those already experiencing symptoms.

Interestingly, further analysis, including assessments of repeated events and on-treatment usage of renin-angiotensin-aldosterone system (RAAS) inhibitors, did not alter the primary results. This consistency reinforces the conclusion that while valsartan may not improve overall survival in all systemic RV patients, it does offer a protective effect against clinical events for those who are symptomatic.

The Takeaway: Valsartan's Targeted Benefits

In summary, while valsartan treatment does not lead to improved survival rates in all patients with systemic right ventricle, it is associated with a decreased risk of clinical events in symptomatic patients. These findings suggest a targeted benefit, emphasizing the importance of identifying and treating symptomatic individuals to improve their long-term outcomes. Further research and prospective studies are essential to fully understand the role of valsartan and similar therapies in this specific population.

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Everything You Need To Know

What exactly is a systemic right ventricle and why is it a concern?

A systemic right ventricle refers to the right ventricle taking on the role of the main pumping chamber of the heart, typically the left ventricle. This occurs in conditions like complete transposition of the great arteries (TGA) after an atrial switch procedure, or congenitally corrected transposition of the great arteries (ccTGA). The systemic right ventricle is significant because it is not designed for this high-pressure role, leading to a gradual decline in function and increased risk of heart failure, arrhythmia, and other adverse events. Therefore, finding ways to support and protect the systemic right ventricle is crucial for improving long-term outcomes for affected individuals.

What is valsartan, and how might it help with heart conditions?

Valsartan is a medication that belongs to a class of drugs known as angiotensin II receptor blockers (ARBs). It works by blocking the effects of angiotensin II, a hormone that can cause blood vessels to constrict. By blocking angiotensin II, valsartan helps to relax blood vessels, lower blood pressure, and reduce the workload on the heart. Valsartan is significant because it is one of the renin-angiotensin-aldosterone system (RAAS) inhibitors being explored for its potential to protect the systemic right ventricle in patients with conditions like TGA or ccTGA. However, the effectiveness of valsartan in this specific population has been uncertain, prompting studies like the VAL-SERVE trial to investigate its impact on clinical outcomes.

What was the purpose of the VAL-SERVE trial?

The VAL-SERVE trial was a multicenter randomized controlled trial designed to evaluate the long-term effects of valsartan on clinical outcomes in patients with a systemic right ventricle. In this study, participants were randomly assigned to receive either valsartan or a placebo over a period of three years. The trial aimed to determine whether valsartan could improve overall survival and reduce the occurrence of clinical events such as arrhythmia, heart failure, the need for tricuspid valve surgery, or death. The VAL-SERVE trial is significant because it sought to provide more definitive insights into the potential benefits of valsartan in this vulnerable patient population, addressing the limitations of previous studies with small sample sizes and inconsistent results.

What were the main findings of the VAL-SERVE trial regarding valsartan's impact?

The VAL-SERVE trial revealed that valsartan treatment did not lead to improved overall survival rates in all patients with a systemic right ventricle. However, it was associated with a decreased risk of clinical events in patients who were symptomatic. This suggests that valsartan may offer a protective effect against complications like heart failure or arrhythmia specifically for those individuals already experiencing symptoms related to their systemic right ventricle dysfunction. This finding is important because it highlights the potential for targeted treatment with valsartan in symptomatic patients to improve their long-term outcomes, even if it does not impact survival for all patients with a systemic right ventricle.

What are RAAS inhibitors, and why are they relevant in the context of a systemic right ventricle?

RAAS inhibitors are a class of medications that includes angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and aldosterone antagonists. These drugs work by interfering with the renin-angiotensin-aldosterone system (RAAS), a hormonal system that regulates blood pressure and fluid balance in the body. RAAS inhibitors are significant because they have been shown to have protective effects on the heart and blood vessels in various cardiovascular conditions. In the context of a systemic right ventricle, RAAS inhibitors like valsartan are being investigated for their potential to reduce the workload on the right ventricle, prevent remodeling, and improve clinical outcomes. The inconsistent results from studies on RAAS inhibitors in this population highlight the need for further research to determine the optimal use of these medications.