Anjali Vaidya, MD, is the director of the Advanced Pulmonary Hypertension, Right Heart Failure & CTEPH Program and the Pulmonary Hypertension Fellowship at Temple University Hospital and a professor of medicine at Temple University

Anjali Vaidya, MD

Sotatercept, an activin signaling inhibitor approved for pulmonary arterial hypertension (PAH), continues to build an evidence base spanning exercise capacity, hemodynamics, and hard clinical outcomes. Anjali Vaidya, MD, of Temple University, discussed a 3-pronged framework for understanding the drug's effect on the right ventricle (RV), covering afterload, RV structure, and RV function, in an interview with 

European Society of Cardiology (ESC) Congress 2026

How Sotatercept Reshapes the Right Ventricle in PAH, With Anjali Vaidya, MD

Sotatercept's efficacy is grounded in a pair of pivotal phase 3 trials. The STELLAR trial demonstrated significant improvement in 6-minute walk distance and 8 of 9 secondary end points, supporting US Food and Drug Administration (FDA) approval in 2024, and the more recent ZENITH trial in high-risk patients with PAH found a 76% reduction in the risk of death, lung transplantation, or PAH-related hospitalization, halting enrollment early for efficacy.¹²

Sotatercept's Distinct Effect on RV Afterload in PAH

Vaidya described sotatercept as a fundamentally different mechanism than existing PAH therapies: "It works as an anti-proliferative and really getting to the basis of the pathophysiology of pulmonary arterial hypertension," she said. "We're seeing dramatic improvements and reversals in pulmonary vascular resistance, the load on the right heart... but we are seeing dramatic improvements in all of the clinical markers of pulmonary pressures, right ventricular structure, size, function, biomarkers, and and really so many of the metrics that we have known for many years now that correlate with prognosis and risk assessment."

Asked what changes in pulmonary vascular resistance and other hemodynamic parameters were most informative, Vaidya said the drug's effect is specific to afterload itself, including impedance to flow, vascular resistance, and pulmonary arterial compliance, rather than pressure reduction alone. She noted these parameters are not always measured directly in standard clinical care, despite being central to the hemodynamic abnormalities driving downstream structural and functional changes in the right heart.

Vaidya said the magnitude of this afterload effect distinguishes sotatercept from prior pulmonary vasodilator classes, describing the pattern as fundamentally different and greater in scale than what other PAH therapies have achieved. Despite multiple effective agents across several classes and pathways developed over recent years, she said the activin signaling inhibitor produces a markedly larger reduction in afterload and pulmonary vascular resistance in many patients.

RV Function, Structure, and the Case for Reverse Remodeling

On evidence for RV function improvement specifically, rather than simply reduced workload, Vaidya pointed to a broad set of metrics. "We're seeing improvements in RV work, the magnitude of energy generated by the right ventricle in... every heartbeat of... stroke volume into the pulmonary artery. We're seeing improvements in RV size. We're seeing improvements in RV to LV relationships in size. We're seeing improvements in RV fractional area change. We're seeing improvements in biomarkers of NT-proBNP and BNP. We're seeing dramatic improvements as well in tricuspid regurgitation, another marker of overall right heart performance," she explained.

On RV structure specifically, Vaidya said reverse remodeling encompasses right ventricular size, right ventricle-to-left ventricle relationships, and end-diastolic and end-systolic volumes. She acknowledged some of these changes are likely related to the drop in afterload, but noted the durability of the improvements raises the possibility of an intrinsic effect on the right ventricle beyond load reduction alone, an area she said warrants further study.²

Asked which of the 3 domains, afterload, structure, or function, is the primary driver of clinical benefit, Vaidya described them as inseparable. "The pathogenesis begins in the afterload, in the pulmonary arterial circulation, but the disease manifests in the structure and performance of the right side of the heart," she said. "You look at the right heart to see what's happening in the pulmonary circulation, and the coupling of the two together is really what... manifests in the greatest long-term benefit for our patients."

Editors’ note: Vaidya reports relevant disclosures with Johnson & Johnson, Merck, and United Therapeutics.

Hoeper MM, Badesch DB, Ghofrani HA, et al; STELLAR Trial Investigators. Phase 3 trial of sotatercept for treatment of pulmonary arterial hypertension. N Engl J Med. 2023;388(16):1478-1490. doi:10.1056/NEJMoa2213558

Humbert M, McLaughlin VV, Badesch DB, et al. Sotatercept in patients with pulmonary arterial hypertension at high risk for death. N Engl J Med. 2025;392(20):1987-2000.

Videos

Anjali Vaidya, MD, breaks down sotatercept's distinct effects on RV afterload, structure, and function in pulmonary arterial hypertension.

Sotatercept's 3-Pronged Effect on the Right Ventricle in PAH, With Anjali Vaidya, MD

The Mechanics Behind PAH Diagnosis and Management, With Anjali Vaidya, MD

In 2022, the European Society of Cardiology (ESC) released a set of comprehensive clinical guidelines for the detection and management of 

, emphasizing the importance of a multidisciplinary approach.

American College of Cardiology (ACC) Scientific Sessions 2026

 in New Orleans, Louisiana, Anjali Vaidya, MD, assistant dean at the Lewis Katz School of Medicine and director of advanced pulmonary hypertension, right heart failure, and the CETPH Program at Temple Health, spoke on the implementation of these guidelines. The editorial team at 

 met with Vaidya at the conference to learn more.

“The guidelines have evolved a lot over the years, which has been a wonderful thing to see,” Vaidya told 

. “But the inclusion of imaging modalities, and particularly electrocardiography, has really expanded in those guidelines. More and more advancement is being made, and more parameters are being included – I think we’ll continue to see that grow even further with the next iteration of guidelines.”

The ESC guidelines focus heavily on reanalyzing the hemodynamic definition of PAH. The authors officially updated the condition’s classification, repositioning vasoreactive patients with idiopathic PAH and developing a new algorithm for earlier detection of PAH in the community. The document also posits new, expedited screening and referral strategies.

Vaidya notes, however, that the most impactful aspect of the current guidelines is the emphasis on imaging in patients with PAH. Echocardiographic and cardiac magnetic resonance imaging (cMRI) parameters are proposed within the document, aiming to help clinicians monitor right ventricle function during the disease’s progression.

“The highest yield of imaging modality for pulmonary hypertension diagnosis is going to be echocardiography, or ultrasound of the heart, from an imaging perspective,” Vaidya said. “This is embedded in all of the pulmonary hypertension guidelines for diagnosis, and there are a lot of different parameters that can be interpreted to give us clues into the diagnosis of pulmonary hypertension.”

Vaidya also provides advice for clinicians entering the sphere of PAH management. She guides newcomers to make themselves familiar with the actual data of their patients rather than allowing technology to manage the numbers. Vaidya emphasizes the importance of being able to interpret data oneself to avoid mechanical errors or complications and to become more familiar with the condition and its effects.

“The most important thing is to practice and become comfortable with looking at the imaging directly rather than relying on reports,” Vaidya said. “There’s so much information available when you look at the pictures of cardiovascular structures, whether that’s on chest X-ray or CT scan or echocardiography, that is sometimes nuanced and subtle, so the biggest first step is to take a dive into it and open those images directly to become more and more comfortable with interpreting and not missing clues.”

Editors’ Note: Vaidya reports disclosures with Bayer, Janssen, Merck, and United Therapeutics.

Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. European Heart Journal. 2022;43(38):3618-3731. 

Vaidya discusses the 2022 pulmonary arterial hypertension guidelines and how they can be made more accessible for clinicians just entering the field.

Shifting Focus to Pulmonary Hypertension in Right Heart Assessment, With Anjali Vaidya, MD

In March 2025, the American Society of Echocardiography introduced a revised version of its Echocardiographic Assessment of the Right Heart Guidelines, which highlighted 

 as a critical indicator in patients with or at risk for 

Right heart adaptation to pulmonary hypertension is a major determinant for clinical outcomes, morbidity, and mortality in patients with, or at risk of, cardiopulmonary disease. The hemodynamic definition of pulmonary hypertension was recently updated, setting it at a resting mean pulmonary artery pressure (mPAP) >20 mm Hg, which was done in response to extensive evidence of adverse outcomes and mortality in patients with mPAP between 21 and 24 mm Hg.

The updated guidelines were presented and broken down at the Pulmonary Hypertension Professional Network Symposium by Anjali Vaidya, MD, director of the advanced pulmonary hypertension, right heart failure & CTEPH program and the pulmonary hypertension fellowship at Temple University.

 met with Vaidya to discuss her presentation and how clinicians should interpret and utilize these new guidelines to provide better and more efficacious treatment for their patients.

“There is an emphasis on using the echocardiogram, not just for initial diagnosis, but for long-term follow-up of patients to really get a finer, more accurate, precise assessment of a patient’s overall risk with pulmonary hypertension,” Vaidya told 

. “And the shift has really happened in the field away from simply relying on how a patient feels and how far they can walk, to looking at the right side of the heart in very specific detail to determine if patients have adequately reached their lowest risk status.”

In addition to these changes, the stated goals of the guideline revision are as follows:

To describe the updated pulmonary hypertension classification and how the right heart adapts to emerging PVD, focusing on structural and functional changes in response to increased afterload

To define optimal acoustic windows and echocardiographic views and parameters required for right heart evaluation

To provide reference values for normality and grade abnormality

To present recommendations for assessing tricuspid and pulmonic valve disease and special considerations in pulmonary hypertension

To propose standard image acquisition and reporting for right-sided measures in clinical practice

To establish the role of echocardiography in screening, detection, and monitoring of therapeutic response and prognostication of pulmonary hypertension.

Additionally, the authors included updated equations and methods by which clinicians can calculate and measure other critical factors, including pulmonary vascular resistance, pulmonary artery end-diastolic pressure, and right atrial pressure.

“These guidelines and the increased awareness of applying these clinical principles using echocardiography should lead to patients getting more high-level expert care,” Vaidya said. “The goal is not to just help them feel better when they’re worse, but to maintain their low-risk status and wellness for an even longer period of time.”

Mukherjee M, Rudski LG, Addetia K, et al. Guidelines for the Echocardiographic Assessment of the Right Heart in Adults and Special Considerations in Pulmonary Hypertension: Recommendations from the American Society of Echocardiography. J Am Soc Echocardiogr. 2025;38(3):141-186. 

Vaidya describes the prognostic approach to pulmonary hypertension in the revised Echocardiographic Assessment of the Right Heart Guidelines.

Anjali Vaidya, MD

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