Orchestra BioMed’s AVIM Therapy Studied for Impact on Diastolic Dysfunction

February 18, 2025—Orchestra BioMed Holdings, Inc. recently announced the presentation of data on the benefits of atrioventricular interval modulation (AVIM) therapy for patients with diastolic dysfunction (DD). The company stated a retrospective analysis of data from the MODERATO II study demonstrated that AVIM therapy significantly improved echocardiographic (echo) markers of DD in hypertensive patients.

“Effects of Atrioventricular Interval Modulation (AVIM) Therapy in Subjects with Hypertension and Diastolic Dysfunction” was delivered by Marat Fudim, MD, in a late-breaking clinical science session at the THT 2025, the Technology and Heart Failure Therapeutics conference held February 11-13 in Boston, Massachusetts. Dr. Fudim is an advanced heart failure cardiologist at Duke Health in Durham, North Carolina.

According to the company, the retrospective, treatment-blinded analysis of MODERATO II assessed the impact of 6 months of AVIM therapy on systolic blood pressure (SBP) and echo markers of 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, noted the company.

As summarized in the Orchestra BioMed press release, the study showed that—using key measures of diastolic function—AVIM therapy significantly reduced office and ambulatory SBP in patients with DD through 6 months.

Key findings presented at THT 2025 included the following:

• Ambulatory SBP was reduced in AVIM-treated DD+ patients (n = 12) by 8.3 ± 9.7 mm Hg (P < .01 vs baseline) compared to 2.2 ± 9.8 mm Hg in the control DD+ group (n = 10).
• Office SBP was reduced in AVIM-treated DD+ patients by 12.1 ± 12.8 mm Hg (P < .01 vs baseline) compared to an increase of 2.9 ± 26.4 mm Hg in the control DD+ group (n = 10).
• SBP reduction was similar in patients with and without DD.

Additionally, significantly improved key measures of DD included the following:

• In patients with DD, AVIM therapy demonstrated favorable echo changes consistent with improved myocardial relaxation and diastolic compliance.
• Compared to DD+ control patients, AVIM-treated DD+ patients experienced a significant increase in e’ (from 5.9 ± 2.0 to 8.8±3.4 cm/sec; P < .01) consistent with an improvement in left ventricular relaxation and a significant increase in E/A—early (E wave) and late (A wave)—ratio (from 0.86 ± 0.39 to 1.60 ± 0.84; P < .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.

“For many patients with long-standing hypertension, the heart can undergo structural and functional changes that result in DD, the progression of which is directly linked to the development of heart failure,” commented Dr. Fudim in the company’s press release. “By reducing systolic blood pressure and favorably impacting intracardiac pressures and volumes, AVIM therapy directly affects diastolic filling and myocardial relaxation.”

Dr. Fudim continued, “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.”

Orchestra BioMed advised that AVIM therapy is an investigational therapy compatible with standard dual-chamber pacemakers designed to substantially and persistently lower blood pressure. It has been evaluated in pilot studies in patients with hypertension who are also indicated for a pacemaker.

The company stated that MODERATO II is a double-blind, randomized pilot study showing that patients treated with AVIM therapy experienced net reductions of 8.1 mmHg in 24-hour ambulatory SBP and 12.3 mmHg in office SBP at 6 months when compared to control patients.

Additionally, the company’s BACKBEAT global pivotal study of bradycardia pacemaker with AVIM for blood pressure treatment that will further evaluate the safety and efficacy of AVIM therapy in lowering blood pressure in a similar target population of patients who have been indicated for, and recently implanted with, a dual-chamber cardiac pacemaker.