Orchestra BioMed has announced the publication of data in the Journal of the American College of Cardiology: Clinical Electrophysiology from a pressure-volume (PV) loop study demonstrating favourable hemodynamic effects of atrioventricular interval modulation (AVIM) therapy in pacemaker-indicated patients with uncontrolled hypertension.
AVIM therapy is currently being evaluated in the BACKBEAT global pivotal study, which Orchestra BioMed is conducting in collaboration with Medtronic, to support potential future global regulatory approvals and commercialisation of AVIM therapy-enabled devices.
The publication reports findings from an invasive PV loop analysis in 16 hypertensive pacemaker-indicated subjects, as well as non-invasive PV loop analysis from a subgroup of subjects (n=32) from the MODERATO II study receiving chronically administered AVIM therapy.
The analyses demonstrated that AVIM therapy reduced systolic blood pressure (SBP) acutely by decreasing cardiac preload and effective arterial elastance unrelated to pacing lead location, while also improving left ventricular (LV) end-diastolic and end-systolic volumes. Chronically administered AVIM therapy demonstrated sustained reductions in SBP and end-diastolic volume, indicative of favourable reverse LV remodelling. Results also demonstrated consistently favourable haemodynamic effects using traditional right ventricular (RV) and conduction system pacing (CSP) lead placements.
Daniel Burkhoff, director, heart failure, hemodynamics, and MCS research, Cardiovascular Research Foundation (CRF) and a manuscript author commented: “Pressure-volume loop analysis is regarded as the gold standard for assessing systolic and diastolic function as well as reverse remodelling. These results provide powerful insights on the impact of AVIM therapy to both decrease blood pressure and favourably impact ventricular end-diastolic volume without compromising cardiac output or increasing workload.
“Notably, these favourable effects were observed consistently and with different pacing lead locations, demonstrating the versatility of AVIM therapy. Publication of these data in a prestigious peer-reviewed journal such as JACC: Clinical Electrophysiology provides further validation from the clinical community reinforcing the therapeutic rationale behind AVIM therapy and further highlighting its potential to deliver differentiated clinical benefit for patients with uncontrolled hypertension.”
Key findings include significantly reduced (p<0.05) SBP, with average decreases of 17.1mmHg (AVIM via RV pacing) and 19.2mmHg (AVIM via CSP), compared to 1.7mmHg with standard dual-chamber pacing. The study also reported improved left ventricular haemodynamics with both RV pacing and CSP, respectively, compared to standard pacing: end-diastolic volume significantly decreased by 12.6mL and 18.6mL compared to 1.4 mL, end-systolic volume significantly decreased by 11mL and 14.1mL compared to an increase of 1.8mL, and end-diastolic pressure significantly decreased by 2.1mmHg and 3.9 mmHg, compared to an increase of 0.3 mmHg.
Investigators also reported significantly reduced (p<0.05) cardiac workload: stroke work decreased by 1,596mL (RV) and 1,870mL (CSP), compared to 42mL (standard pacing), with minimal impact on stroke volume, and significantly reduced total peripheral resistance (TPR, measured by effective arterial elastance [Ea]), which decreased by 0.23mmHg/mL (RV) and 0.31mmHg/mL (CSP), compared to an increase of 0.04 mmHg/mL (standard pacing).
Yuval Mika, executive vice president, Bioelectronic Therapies at Orchestra BioMed, said: “The publication of the PV loop data in JACC: Clinical Electrophysiology marks another important milestone showcasing AVIM therapy’s potential ability to significantly reduce blood pressure and favourably impact cardiac function in hypertensive patients with increased cardiovascular risk. The consistent reduction seen in cardiac preload, as well as cardiac afterload with both CSP and RV lead placements in these pilot studies demonstrates that AVIM therapy’s mechanism of action works regardless of lead location.
“Furthermore, acute and chronic PV loop results indicate AVIM therapy’s potential to induce positive reverse remodelling of ventricular hypertrophy, highlighting potential to prevent or even treat heart failure. We continue to believe that AVIM therapy has the potential to reshape the standard of care for higher risk patients with uncontrolled hypertension in the pacemaker population and beyond.”
