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Evaluation of the BIOTRONIK AutoAdapt Algorithm for Continuous Automatic Adaptive Cardiac Resynchronization (BIO|Adapt)

Evaluation of the BIOTRONIK AutoAdapt Algorithm for Continuous Automatic Adaptive Cardiac Resynchronization (BIO|Adapt)

197

In the BIO|Adapt submodule, the first and the last patients were enrolled on August 31, 2021 and on July 5, 2024, respectively. The last patient-out was on July 25, 2025. In the matchedcontrol patients cohort from BIO|STREAM.HF, the first patient was enrolled on May 16, 2018, last patient on the April 30, 2024, and last patient-out was on June 11, 2025. Overall, 197 patients participated in the BIO|Adapt submodule study. Of these, 174 had a regular study exit whereas 23 patients prematurely ended study participation. Of the 197 patients, 164 patients had AutoAdapt ON and were allocated to the treatment group, and 33 patients, either without the CRT AutoAdapt feature or with the AutoAdapt OFF, were allocated to the control group. The ITT analysis population of the BIO|Adapt patients included 162 patients from the treatment group and 31 from the control group. In addition, 121 matched-control patients from the BIO|STREAM.HF registry were included after PSM, and pooled with the control group, totalling 152 patients (pooled control group). Finally, the ITT analysis cohort included 314 patients; the PP population (n = 305) included 153, 31 and 121 patients, respectively.

At baseline, the mean age of patients were 69.1 +/- 9.2 years, and 68.7 +/- 8.0 years for patients in the treatment (n = 162) and pooled control group (n = 152), respectively. Patients were predominantly male (67.9% in the treatment group, and 75.7% in the pooled control group) and were mainly in NYHA class II (53.4% in the treatment group, 48.7% in the pooled control group) or III (42.9% in the treatment group, and 46.7% in the pooled control group). Ischemic etiology of HF was 36.4% and 42.8% in the treatment and pooled control groups, respectively. Documented AV-block was reported in 25.8% of the patients, 24.7% in the treatment group, 27.0% in the pooled control group. Of these, 77.5% (treatment group), and 63.4% (pooled control group) had a documented I degree AV block. Bradycardia pacing indication accounted for 11.7% in the treatment and 18.4% in the pooled control group. The proportion of patients that have had a cardiac device prior to baseline or still had a non-CRTdevice implanted at baseline was 6.8% and 11.2% in the treatment and pooled control group, respectively. Standard CRT indication in sinus rhythm was the most frequent type of CRT indication (95.7% and 87.5% in the treatment and pooled control groups). No failed attempt was reported in initial LV lead implantations in any of the study groups. Lead parameters for the atrial, ICD and LV leads were within the normal and expected ranges at implantation in both treatment and pooled control groups. The mean baseline LVEF was 27.6% and 27.1% in the treatment, and pooled control group, respectively with LVEDD and LVESD prior to implantation of 63.4 mm and 54.8 mm in the treatment group, and 66.4 mm and 57.5 mm in the pooled control group, respectively.

<Unplanned hospitalization for worsening heart failure> Incidence rates for unplanned hospitalizations for WHF (according to investigator assessment) were 2.6% (4/153) and 6.6% (10/152) in the treatment and pooled control group, respectively. The treatment group showed a numerically lower hazard of unplanned hospitalization for WHF compared to the pooled control group (HR 0.38, 95% CI 0.12 1.22; p=0.103). However, the estimated 62% relative reduction only approached statistical significance. <Re-admission after first hospitalization for worsening heart failure> From 14 patients with a prior first hospitalization (10 in the control group and 4 in the treatment group), only 4 had at least one re-admission. One patient from the treatment group had 3 readmissions, whereas 3 patients from the pooled control group had one re-admission each. <Adverse device effects related to the CRT AutoAdapt feature> There was no adverse device effect classified as probably or causally related to the CRT AutoAdapt. Two deaths initially assessed by the sponsor's vigilance department as possibly device-related were subsequently adjudicated as unlikely related to the CRT AutoAdapt algorithm. <Results related to other data of interest: The incidence of AF at least in two consecutive days throughout the 12-month> Any HM messages between implantation and end date available were received in 97.4% and 96.7% of patients in the treatment, and pooled control group, respectively. The patients in the treatment group were associated with an approximately 80% lower hazard rate of developing AF compared with the pooled control group (5/149 vs. 24/147; HR 0.20, 95% CI (0.08 to 0.53), P<0.0012) <Results related to device or procedure-related adverse events or deficiencies> There were 7 non-serious adverse device effects (ADEs), and 23 serious device or procedure related adverse device effects (SADEs). Eight deaths occurred during the study of which 3 were related to the device: 2 patients died due to unknown reasons and were assessed as possibly related to the device, and 1 patient died from a CRT-D pocket infection and subsequent circulatory failure and was deemed causally related to the device. However, the contribution of the AutoAdapt algorithm is considered unlikely in the 2 cases with an unknown reason of death. No device deficiencies with or without an SADE potential were reported.

<Primary Endpoint: Clinical composite Packer score> The primary endpoint was examined as per protocol (PP). At 12-month FU, 73.7% of the patients in the treatment group had an improved CCS vs. 68.4% in the pooled control group, reaching non inferiority (1-sided P=0.002). Non-inferiority was also shown in the ITT population. The CCS was analyzed in four subgroups of patients: with and without history of AF and with and without history of AV block. <Secondary Endpoint> Secondary Endpoint 1: Acute hemodynamic effect of the AutoAdapt CRT feature CRT AutoAdapt and echo-optimized AV delay settings resulted in similar cardiac performance as demonstrated by a high concordance correlation coefficient between aortic velocity time integrals at CRT AutoAdapt (0.7) and echo settings at pre-hospital dischar correlation coefficient = 0.84; P<0.001). Secondary Endpoint 2: Change in LVEF / LVEDD(V) / LVESD(V) between baseline and12-month FU Absolute differences (delta) in LVEF from baseline to 12-month FU between treatment and pooled control group were not significant (12.1% vs. 13.8%, P=0.207). Reverse remodeling was observed in patients with the AutoAdapt algorithm after 12 months FU with an absolute decrease in all 4 parameters (absolute decreases: -3.4 mm for LVEDD, -5.7 mm for LVESD, -44.1 ml for LVEDV, and -45.3 ml LVESV, P<0.001). However, the difference in the mean delta in LVEDV from baseline to 12-month follow-up between the 2 groups did not reach statistical significance for any of the variables. In the treatment group, 70.1% of patients were LVEF responders (absolute increase > 5%) and 92.1% were LVESV responders (improvement > |15%| relative). Similarly, 77.9% and 87.0% of patients in the control group were LVEF and LVESV responders, respectively. No statistically significant differences in the response rates between the two groups were observed. Secondary Endpoint 3: Change in NYHA class through 12 months Of the 142 patients with data on NYHA in the treatment group, 90 patients (63.4%) improved in NYHA classification whereas only 2 patients (1.4%) showed a worsening in the NYHA class. Of the 144 patients with data on NYHA class in the pooled control group, 91 patients (63.2%) improved in NYHA classification whereas only 8 patients (5.6 %) showed a worsening in NYHA. Intraindividual differences within each group in the NYHA class from baseline to 12-month FU reached statistical significance. However, when groups were compared, no statistically significant changes in the NYHA functional class from baseline to 12-month FU were observed. Secondary Endpoint 4: Percentage of LV-only pacing at 12-month FU in the treatment group The median LV-only pacing was 35.8% and the percentage of patients with an LV>=80% was 29.5%.

The BIO|Adapt submodule study showed that the percentage of patients in the CRT AutoAdapt group with an improved CCS or modified CCS at 12 months was at least as high as in the pooled control group. In conclusion, the CRT AutoAdapt algorithm is safe and its activation provides a clinical benefit across a variety of primary and secondary endpoints that was at least equivalent to conventional CRT device programming.

Sept. 30, 2026

No

No plan to share IPD.

https://jrct.mhlw.go.jp/latest-detail/jRCTs032210268

Kato Ritsushi

Saitama Medical University International Medical Center

1397-1, Yamane, Hidaka Shi, Saitama Ken, 350-1298, Japan

ritsn@saitama-med.ac.jp

Kato Ritsushi

Saitama Medical University International Medical Center

1397-1, Yamane, Hidaka Shi, Saitama Ken, 350-1298, Japan

+81-42-984-4302

ritsn@saitama-med.ac.jp

Complete

Aug. 23, 2021

Interventional

non-randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

- Indication for de novo implantation or upgrade to a CRT-D device
- Enrolled in BIO|STREAM.HF but not yet implanted with or upgraded to CRT-D
- LVEF < 35%
- QRS > 120 ms
- NYHA II-IV
- Atrial heart rate during sinus rhythm at rest below 100 bpm based on pre-enrollment ECG.
- Patient is able to understand the nature of the study and willing to provide written informed
consent

- Planned implantation or previous implantation with a BIOTRONIK DX ICD lead
- History of persistent/permanent AF
- complete AV-block

Both

Heart Failure

The group allocation will be determined by the activation or not of the algorithm from medical criteria.
For AutoAdapt Group: The assessment of the acute hemodynamic effect of AutoAdapt must be performed in PHD Follow-Up. The final device programming has AutoAdapt feature ON as mandatory setting, or AV Adapt in those cases where the investigator sees a contraindication for only LV pacing in this time.

The 12 month FU (plus or minus 30 days) after implantation shall be scheduled in-office at the clinic. The following data shall be collected:
- Patient self-assessment
- Echocardiography parameters (LVEF/LVESD(V)/LVEDD(V))
- Device programming settings to verify the correct programming of the CRT AutoAdapt algorithm with respect to the group assignment in the study.

Heart Failure

D006333

CRT-responder rate at 12 months based on improvement in clinical composite score developed by Packer.

1. Acute hemodynamic effect of AutoAdapt
2. Change in LVEF / LVEDD(V) / LVESD(V) between baseline and 12 month FU
3. Change in NYHA class through 12 months
4. Percentage of LV only pacing at 12 month FU
5. Unplanned hospitalization for worsening heart failure
6. Re-admission after first hospitalization for worsening heart failure
7. Adverse device effects related to the CRT AutoAdapt feature

+81-49-276-1662

July. 27, 2021

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