Orchestra BioMed Announces Data on Its AVIM Therapy

Orchestra BioMed Holdings, a biomedical company accelerating high-impact technologies to patients through risk-reward sharing partnerships, presented late-breaking data on the benefits of atrioventricular interval modulation (AVIM) therapy on patients with diastolic dysfunction.

The retrospective analysis of data from the MODERATO II study demonstrated that AVIM therapy significantly improved echocardiographic (Echo) markers of diastolic dysfunction, an important component in the development of heart failure, in hypertensive patients.

The oral presentation was given at the Technology and Heart Failure Therapeutics (THT) 2025 Conference in Boston, Massachusetts. The presentation was titled “Effects of Atrioventricular Interval Modulation (AVIM) Therapy in Subjects with Hypertension and Diastolic Dysfunction” and was presented by Marat Fudim, M.D., M.H.S.​ Advanced Heart Failure Cardiologist at Duke Health.

“The late-breaking data shared at THT present a broader view of the potential benefits of AVIM therapy for patients with uncontrolled hypertension and increased cardiovascular risk. These findings provide further evidence that AVIM therapy, in addition to significantly reducing systolic blood pressure, may also favorably influence ventricular function in important ways for patients with diastolic dysfunction and at risk for heart failure,” said Avi Fischer, M.D., Senior Vice President of Medical Affairs and Innovation at Orchestra BioMed. 

A retrospective, treatment-blinded analysis of MODERATO II assessed the impact of six months of AVIM therapy on systolic blood pressure (SBP) and Echo markers of diastolic dysfunction (DD) using core lab Echos with independent blinded adjudication. 

Patients were classified as with DD (DD+) or without DD (DD-) using ​the American Society of Echocardiography Guidelines. From the MODERATO II study cohort (n=47), 36 patients had technically sufficient Echo data, and 61% of this group (22/36) had Echo evidence of DD.

Key Findings

AVIM Therapy Significantly reduced office and ambulatory SBP in patients ​with DD through 6 months and improved key measures of diastolic dysfunction​.

• Ambulatory SBP (“aSBP”) was reduced in AVIM-treated DD+ patients (N=12) by 8.3±9.7 mmHg (p<0.01 vs baseline) compared to 2.2±9.8 mmHg in the control DD+ group (N=10)
• Office SBP (“oSBP”) was reduced in AVIM-treated DD+ patients by 12.1±12.8 mmHg (p<0.01 vs baseline) compared to an increase of 2.9±26.4 mmHg in the control DD+ group (N=10)
• SBP reduction was similar in patients with and without DD
• In patients with DD, AVIM therapy demonstrated favorable Echo changes consistent with improved myocardial relaxation and diastolic compliance. AVIM-treated DD+ patients experienced a significant increase in e’ (from 5.9±2.0 to 8.8±3.4cm/sec; P<0.01) consistent with an improvement in left ventricular relaxation and a significant increase in E/A (from 0.86±0.39 to 1.60±0.84; P<0.01) consistent with improved passive filling of the left ventricle despite reduced filling time (the designed effect of AVIM therapy) with no significant changes in left atrial size.

Fischer added, “This could provide a new paradigm for the treatment of hypertension and its many associated risks in pacemaker-indicated patients and other higher risk populations, offering the opportunity to potentially intervene earlier in disease progression.”

Dr. Fudim commented, “For many patients with long-standing hypertension, the heart can undergo structural and functional changes that result in diastolic dysfunction, the progression of which is directly linked to the development of heart failure. By reducing systolic blood pressure and favorably impacting intra-cardiac pressures and volumes, AVIM therapy directly affects diastolic filling and myocardial relaxation. This analysis of MODERATO II data provides exciting insights that suggest that, beyond lowering systolic blood pressure, AVIM therapy improves diastolic function and leads to favorable ventricular remodeling. Given the strong link between uncontrolled hypertension, diastolic dysfunction, and heart failure, these findings highlight the opportunity to intervene earlier and leverage AVIM therapy for the prevention of heart failure.”

“We are eager to continue exploring the clinical effects of AVIM therapy through the ongoing BACKBEAT global pivotal study in which we fully expect to see many hypertensive patients like these that are not adequately controlled with antihypertensive medication and also have diastolic dysfunction and increased risk for heart failure,” Fischer concluded.