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Article

Biventricular Cardiac Resynchronization Therapy with Atrial Sensing but No Atrial Lead: A Prospective Registry of Patients, Complications, and Therapy Responses

by
Christof Kolb
1,2,*,
Endre Zima
3,
Martin Arnold
4,
Marián Fedorco
4,5,
Hendrik Bonnemeier
6,
Thomas Deneke
7,
Burghard Schumacher
8,
Peter Nordbeck
9,
Clemens Steinwender
10,
Theresa Storz
1,
Béla Merkely
3,
Lars Anneken
4,
Angelika Felk
11 and
Carsten Lennerz
1,12 on behalf of the BIO|REDUCE Study Investigators
1
Department of Cardiology, German Heart Centre, TUM University Hospital, Technical University of Munich, 80636 Munich, Germany
2
Department of Cardiology, Rhythmology, Angiology and Intensive Care Medicine, Heart Centre Osnabrück, Hospital Osnabrück, Westphalian Wilhelms University of Münster, 49076 Osnabrück, Germany
3
Heart and Vascular Center, Semmelweis Medical University, 1122 Budapest, Hungary
4
Department of Cardiology, Friedrich-Alexander-Universität Erlangen-Nuremberg, 91054 Erlangen, Germany
5
Department of Cardiology, University Hospital Olomouc, 77900 Olomouc, Czech Republic
6
Medical Faculty, Christian-Albrechts-University, 24105 Kiel, Germany
7
Heart Center Bad Neustadt, 97616 Bad Neustadt, Germany
8
2nd Department of Medicine, Westpfalz-Klinikum, 67655 Kaiserslautern, Germany
9
Internal Medicine I, University Hospital Würzburg, 97080 Würzburg, Germany
10
Department of Cardiology, University Hospital, Medical Faculty, Johannes Kepler University, 4020 Linz, Austria
11
Biotronik, 12359 Berlin, Germany
12
Partner Site Munich Heart Alliance, German Centre for Cardiovascular Research (DZHK), 80636 Munich, Germany
 
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*
Author to whom correspondence should be addressed.
J. Clin. Med. 2025, 14(14), 5009; https://doi.org/10.3390/jcm14145009
Submission received: 21 May 2025 / Revised: 24 June 2025 / Accepted: 30 June 2025 / Published: 15 July 2025
(This article belongs to the Section Cardiology)
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Abstract

Background/Objectives: Patients with normal sinus rhythms undergoing cardiac resynchronization therapy defibrillator (CRT-D) implantation may benefit from a novel two-lead CRT-D system (CRT-DX), which features an atrial sensing dipole integrated into the right ventricular lead. This single-arm, international, non-controlled investigation focused on the safety and clinical efficacy of CRT-DX devices in CRT-D candidates who do not require atrial pacing. Methods: Patients indicated for CRT-D implantation (resting heart rates > 40 bpm and ≥100 bpm during exercise, no second or higher-degree AV block, and no history of persistent or permanent atrial fibrillation) were enrolled across 21 sites in four European countries. The primary endpoint was the need for an additional RA lead implantation within 12 months. Secondary endpoints comprised any invasive re-intervention to the CRT-DX system or infection. Results: Among the 110 patients (mean age 62 years, 70% male), 60% had an underlying non-ischemic cardiac disease. During 12 months of follow-up, RA lead implantation was required in two patients for atrial undersensing or chronotropic incompetence (RA lead implantation-free rate: 98.2% (95% CI: 92.7–99.5%)). Atrial sensing amplitudes were stable (mean: 4.7 ± 1.7 mV), AV-synchrony was maintained at >99%, and the median percentage of biventricular pacing exceeded 98%. The left ventricular ejection fraction improved by an absolute 14.7%. Conclusions: Using simple, clinically applicable inclusion criteria, the two-lead CRT-DX system demonstrated a low rate of subsequent RA lead implantations (1.8%) and maintained adequate RA sensing amplitudes throughout the observation period. The two-lead CRT-DX concept appears to be a feasible alternative for patients with preserved chronotropic competence.

1. Introduction

Cardiac resynchronization therapy (CRT) with biventricular pacing is an established treatment for patients with a wide QRS complex and severe, symptomatic heart failure despite optimal pharmacological therapy. CRT benefits are strongly supported by current clinical guidelines [1,2] and robust evidence from randomized trials, which consistently demonstrate reductions in morbidity and mortality compared to drug therapy alone [3,4,5]. Conventional CRT or CRT defibrillator (CRT-D) treatment requires a complex implanted system with three leads and is thus associated with a relevant rate of lead-related complications. Comparisons between single- and dual-chamber implantable cardioverter-defibrillators suggest that complication rates increase with the number of leads [6,7]. A simplification of the CRT-D system may therefore represent a strategy for reducing the complication rates in CRT-D recipients.
A CRT-D system with two leads (the CRT-DX concept) has recently been introduced, in which atrial sensing is provided by two rings placed on the right ventricular (RV) lead at 15 or 17 cm (center of the dipole) from the lead tip. Advanced signal processing by the CRT-DX electronic circuitry, including up to four-fold amplification of the atrial signal, enables adequate atrial sensing even in patients with long-lasting or permanent atrial fibrillation, but the system is not designed to deliver atrial pacing [8,9]. RV and left ventricular (LV) sensing and pacing in CRT-DX devices are performed using the same method as conventional three-lead CRT-D systems.
A potential disadvantage of the CRT-DX concept is the need for late atrial lead implantation in cases of new-onset bradycardia or loss of atrial sensing due to a less stable position of the free-floating atrial dipole. Moreover, there is a lack of standardized criteria for identifying and excluding CRT-DX candidates who might later develop the need for bradycardia pacing.
Clinical data regarding the use of CRT-DX in patients with CRT-D indication and sinus rhythms is still limited [10,11]. The prospective BIO|REDUCE study was designed to evaluate the performance of the CRT-DX system in another population of CRT-D candidates selected using clinically straightforward criteria and treated according to the standard care. The study aimed to determine whether CRT-DX implantation results in a re-intervention rate for atrial leads comparable to that of conventional CRT-D systems and whether the CRT response, facilitated by preserved atrioventricular (AV) synchrony and a high proportion of biventricular pacing, is similar to that of standard CRT-D systems.

2. Methods

2.1. Study Design and Conduction

BIO|REDUCE was a prospective, single arm, non-controlled, post-market observational study (ClinicalTrials.gov Identifier: NCT03839121) conducted at 21 sites in four European countries and in accordance with the Declaration of Helsinki. The study protocol was approved by the ethics committees and authorities for all participating sites according to the country-specific requirements. All patients provided written informed consent before enrollment.

2.2. Patient Enrollment and Follow-Up

Patients were recruited between July 2019 and June 2022. After CRT-DX implantation, they were followed for 12 months through on-site visits at 3, 6, and 12 months. Continuous remote monitoring (Home Monitoring®, Biotronik SE & Co. KG, Berlin, Germany) was applied in all patients.
Inclusion criteria were age ≥ 18 years and an indication for CRT-D implantation according to the ESC Guidelines [12,13]. In addition, the patients had to be in New York Heart Association (NYHA) class II or class III despite optimized pharmacological heart failure therapy and to be in sinus rhythm without a history of persistent or permanent atrial fibrillation. The required sinus rates were >40 bpm at rest and ≥100 bpm during exercise (tested within 3 months before enrollment). Exclusion criteria were (i) sinus node dysfunction or other anticipated circumstances requiring atrial pacing, (ii) the second- or third-degree AV block, or (iii) a premature ventricular contraction rate above 5%.

2.3. CRT-DX System

All patients were implanted with a commercially available CRT-D device (Ilivia, Inlexa, Intica, Rivacor, or Acticor, manufactured by Biotronik SE & Co. KG, Berlin, Germany), a compatible RV defibrillation lead with atrial dipole (RV-DX lead, models Plexa ProMRI S DX 65/15 or 65/17; Biotronik SE & Co. KG, Berlin, Germany), and any LV lead (type and manufacturer freely selected by the implanter). According to the study protocol, implantation of an RV-DX lead was not recommended if the atrial sensing amplitude measured with an external pacing system analyzer during implantation was below 1.0 mV. This cutoff value was based on recommendations derived from an expert survey.

2.4. Rationale and Study Endpoints

The implantation of a CRT-DX system may be beneficial if the rate of right atrial (RA) lead implantations in patients with initial CRT-DX implantation is lower than the re-intervention rate on the atrial lead in a three-lead CRT-D system. Therefore, the implantation of an RA lead for any clinical reason after a successfully concluded initial CRT-DX implantation was defined as the primary endpoint. The three secondary endpoints were any post-implant surgical re-intervention involving (i) any component of the CRT-DX system, (ii) any lead complication, and (iii) device or pocket infection. Additionally, atrial sensing performance and clinical outcome, measured by left ventricular ejection fraction (LVEF) and NYHA class, were assessed at baseline and at 12 months.

2.5. Statistical Methods

For sample size planning, a dislocation rate of RA leads in CRT-D systems of 3% was assumed [14,15,16,17,18]. Assuming a similar implantation rate of RA leads in the CRT-DX system, a sample size of at least 100 patients was calculated to achieve a 95%, 80%, or 58% probability of observing at least 1, 2, or 3 primary endpoints, respectively [19].
Patients in whom implantation of any component of the CRT-DX system failed or in whom the implanter chose to switch to the conventional three-lead CRT-D system (e.g., if atrial sensing amplitude measured by a conventional pacing system analyzer was below 1.0 mV) were excluded from the statistical analysis.
Descriptive statistics are expressed as the mean ± standard deviation or median and interquartile range (IQR) for metric variables, and as the count and percentage for categorical variables. Intraindividual changes in ordinal and metric data were analyzed using the non-parametric Wilcoxon signed-rank test. Event-free rates and 95% confidence intervals (CI) for the primary and secondary endpoints were estimated using the Kaplan–Meier method.
All device-based statistics during follow-up were derived from remote monitoring data. Patient-specific virtual follow-up values were simulated by calculating the average of values obtained through daily messages within a 14-day interval around 30 days (1 month), 183 days (6 months), and 365 days (12 months) after implantation if at least two daily messages were transmitted for the given virtual follow-up point. Descriptive statistics were then performed analogously to the data collected via case report forms.

3. Results

3.1. Patients

Of the 113 patients initially enrolled in the study, 2 were excluded due to failed placement of the LV lead and 1 was excluded after receiving a device not specified in the study protocol. No patient received an RA lead during initial implantation.
At baseline, the patients were 62 ± 12 years old and 77 (70.0%) were male (Table 1). The underlining heart disease was mainly non-ischemic (60.0%), and the mean LVEF was 26 ± 7%. Although the majority of patients (93.6%) received beta-blockers, the mean heart rate at rest was as high as 69 ± 12 bpm. The maximum heart rate at exercise was 116 ± 17 bpm, which was determined through an exercise test (49.5%), 6 min walk test (29.4%), Holter ECG (11.9%), or other ECG methods (9.2%).

3.2. Follow-Up

Of the 110 study patients, 104 were followed for 12 months and 6 were terminated from the study earlier: 1 due to CRT-DX system explantation caused by infection, 2 due to deaths unrelated to the study intervention (car accident and pneumonia), 2 who withdrew informed consent, and 1 was lost to follow-up. The mean follow-up period was 363 ± 68 days.

3.3. Primary Endpoint: Implantation of an RA Lead

Two patients required late RA lead implantation during the observation period. The first patient, initially meeting the inclusion criteria with a resting heart rate of 53 bpm and maximum rate of 107 bpm, developed chronotropic incompetence. Remote monitoring showed a decline in daily mean heart rate from 59 bpm in the first 2 post-operative months to 55 bpm before RA lead implantation at 7.5 months (day 229) post-CRT-DX implantation.
The second patient experienced immediate post-implantation atrial undersensing, with only five valid atrial amplitude measurements (0.6–0.9 mV) in the first month and no subsequent improvement, leading to RA lead implantation at 6.5 months (day 213). This patient’s initial eligibility for CRT-DX was uncertain due to undocumented atrial sensing amplitudes measured by an external pacing system analyzer during implantation, which should have excluded patients with amplitudes < 1.0 mV.
These two cases resulted in an RA lead implantation-free rate at 365 days of 98.2% (CI: 92.7–99.5%).

3.4. Secondary Endpoints

During follow-up, 11 surgical re-interventions related to any component of the CRT-DX system were carried out in 11 patients (10%), which corresponds to an event-free rate of 89.9% at 12 months (CI: 82.4–94.3%). Nine of these surgical re-interventions were related to leads, including two cases of RA lead implantation, three LV lead dislodgements, two RV-DX lead dislodgments, one RV-DX threshold increase, and one pocket infection followed by CRT-DX system explantation (Table 2). The 12-month event-free rate for lead-related re-interventions was 91.7% (CI: 84.6–95.6%), and for pocket infections, it was 99.1% (CI: 93.6–99.9%). The two surgical re-interventions unrelated to leads involved a healing disorder without evidence of infection and device repositioning due to shoulder pain and arm numbness. No lead perforation was reported.

3.5. Atrial Sensing and Atrio-Biventricular Pacing

In the 102 patients who remained in the CRT-DX configuration until the study’s end (excluding 2 patients who transitioned to conventional three-lead CRT-D after RA lead implantation from the original cohort of 104 that was followed for 12 months), the mean daily RA sensing amplitudes, measured remotely, were 4.7 ± 1.7 mV at 1 month, 4.9 ± 1.8 mV at 6 months, and 4.7 ± 1.7 mV at 12 months. The corresponding mean daily minimum values were 4.0 ± 1.7 mV, 4.1 ± 1.7 mV, and 4.0 ± 1.8 mV, respectively. As illustrated in Figure 1, the RA sensing amplitude remained stable within the observational time.
Comparatively, the mean intraoperative RA sensing amplitude measured by the implanted CRT-DX at the final lead position was 6.8 ± 4.4 mV (median: 5.8 mV; IQR: 4.0–8.7). When measured using an external pacing system analyzer—without the advanced signal processing and amplification provided by the CRT-DX—the mean amplitude was 2.8 ± 2.4 mV (median: 2.0 mV; IQR: 1.4–3.0). Notably, the RA sensing amplitudes measured by the external pacing system analyzer were <1.0 mV in four enrolled patients, while data were unavailable for five patients.
The median value of the atrial sensing-triggered ventricular pacing (AS-VP) or atrial sensing followed by intrinsic rhythm (AS-VS) was 99.3% (IQR: 97.8–99.9) at 1 month, 99.4% (IQR: 97.6–100) at 6 months, and 99.8% (IQR: 98.2–100) at 12 months. The median percentage of biventricular pacing was 98.8% (IQR: 94.9–99.8), 98.9% (IQR: 95.1–99.9%), and 98.5% (IQR: 94.6–100), respectively.

3.6. Clinical CRT Response

Paired echocardiographic data from baseline (without CRT) and the study end in the CRT-DX configuration were available for 95 patients. The mean LVEF increased significantly by 14.7% ± 11.0%, rising from 26.1% ± 6.7% at baseline to 40.8% ± 10.7% at the study’s end (p < 0.001, Figure 2).
NYHA class assessments at baseline and the study end in the CRT-DX configuration were available for 85 patients. Among these, 48 patients (56.5%) demonstrated improvement by one (35 patients, 41.2%) or two (13 patients, 15.3%) classes. No changes were observed in 32 patients (37.6%). Five patients (5.8%) experienced a worsening by one class (global p-value < 0.001, Figure 3).

4. Discussion

In this study of 110 CRT-D patients in sinus rhythm who received a CRT-DX system without an atrial lead, only two cases required the addition of an atrial lead during the first year of follow-up. Before implantation, chronotropic competence was assessed using Holter ECG monitoring, a 6 min walk test, or an ergometer test, with patients excluded if their maximum achieved heart rate did not exceed 100 bpm. These findings suggest that the CRT-DX concept may be clinically applicable using a simple decision algorithm.
The BIO|REDUCE study adds data on the use of CRT-DX systems in a standard care setting, while previous studies focused on proof-of-principle and sub-analyses of a study primarily targeting left ventricular lead performance [10,11].
Reducing the complexity of implantable therapeutic devices can simplify their use, lower complication rates, and mitigate costs. In the context of CRT, omitting the atrial lead in patients with sinus rhythm and preserved chronotropic competence is feasible if an atrial dipole on the RV lead ensures AV synchrony. Several recent studies suggested that CRT-DX systems are safe and reliable [8,10,11]. However, concerns remain regarding optimal patient selection, and additional data on the stability of atrial signals and CRT responses with CRT-DX systems would further support their broader clinical adoption.
The BIO|REDUCE study applied the simple clinical selection criteria of a sinus rate > 40 bpm at rest and ≥100 bpm during exercise under individually optimized pharmacological heart failure therapy, combined with the absence of persistent atrial fibrillation or bradycardia–tachycardia syndrome. The need for atrial pacing and subsequent transition to a conventional CRT-D—requiring an additional implantation procedure—was 1.8% during the 12 months of follow-up. In two earlier studies with a total of 157 patients, no patient needed an RA lead implantation was found for the CRT-DX system over more than one year of follow-up [10,11]. This suggests that the RA lead implantation rate is lower than the typical atrial lead re-intervention rates using conventional CRT-D systems [11,15,16,17,20,21,22], although a randomized comparison would be required for a conclusive answer. Notably, one of the two patients requiring an additional atrial lead implantation had received the CRT-DX system despite exhibiting low atrial signal amplitudes during early follow-up—likely detectable at the time of implantation but neglected by the implanter in deviation from protocol recommendations. This underscores the critical importance of strict adherence to CRT-DX selection criteria, which could minimize the need for RA lead upgrades when rigorously applied.
Patients with frequent premature ventricular complexes and those with second- or third-degree AV block were excluded from the CRT-DX study to optimize the data quality of AV-synchronous pacing. These study-related exclusion criteria should not be interpreted as clinically significant restrictions on the use of the CRT-DX system in routine practice.
As secondary endpoints, device- and lead-related re-interventions demonstrated an overall re-intervention rate of 10.0% (only 8.2% were lead-related), including the two patients (1.8%) who reached the primary endpoint of atrial lead implantation. Overall, he lead-related complication rate was comparable to that in previous reports for conventional CRT-D systems [21,22,23], which is consistent with prior CRT-DX studies that also reported device-related re-intervention profiles similar to those with conventional CRT-D systems [10,11].
Overall, a high rate of atrio-biventricular synchronous pacing (>98%) was observed in the BIO|REDUCE study, as would be expected for conventional CRT-D systems equipped with an RA lead, and it meets the expectation to be as high as possible [2,24]. This high biventricular pacing percentage during follow-up is attributable to the stable atrial signal amplitudes, which averaged 4.7 mV throughout the study. Variations in signal amplitudes were noted; however, the minimum values derived from the daily data transmissions were well above the margin required to ensure reliable atrio-biventricular pacing. Furthermore, these findings suggest that atrial signal quality is also adequate for the detection of atrial tachyarrhythmias in this patient population [8]. The results of the present study highlight the efficacy of the CRT-DX system’s advanced signal processing algorithm and align with those of previous investigations showing stable and adequate atrial sensing across different body positions over time in single-chamber systems [25].
The relatively large post-processed atrial signal amplitudes should not lead to the assumption that any signal can be appropriately processed. There is a lower threshold below which signal processing becomes challenging for the algorithm. In this study, a cutoff of 1.0 mV for atrial signal amplitude, measured using a standard pacing system analyzer, was recommended for lead position acceptance. This threshold was not met in four patients, one of whom experienced atrial undersensing of sinus rhythm during follow-up. Therefore, the value of 1.0 mV seems to be a threshold that should not be undercut, and it is advisable to achieve larger signal amplitudes.
Adequate atrial signals for atrio-biventricular synchronous pacing are a pre-requisite for a CRT response. In this study, CRT responses were measured as changes in LVEF and NYHA class between study inclusion and the 12-month follow-up. A statistically significant increase in LVEF by a mean of 14.7% was observed in the patients with paired data available at both time points, documenting a robust response to CRT with a well-functioning CRT-D system. Large CRT trials typically report an absolute increase in LVEF of approximately 4–11% [4,26,27]. Whether the greater improvement observed in our study reflects the patient selection criteria, such as chronotropic competence during sinus rhythm as a surrogate for less advanced heart disease, or is due to random effects related to the limited study size remains uncertain.
Corresponding to the significant increase in LVEF observed in our study cohort, the NYHA class showed both clinical and statistically significant improvements. More than half of the patients achieved an improvement of at least one NYHA class, while CRT non-response or disease progression were infrequent.
Omitting the atrial lead is not the only emerging strategy for hardware simplification in CRT. Recent advancements have introduced dual-chamber CRT devices with ventricular leads positioned at the His bundle or left bundle branch area to implement conduction system pacing (CSP). Non-randomized studies have shown very promising effects of CSP on heart failure management in patients with traditional CRT pacemaker indications and in preventing heart failure when ventricular antibradycardia pacing is required [22,28,29,30]. These encouraging findings have been further supported by more recent randomized trials [31,32,33]. Currently, CSP primarily targets pacemaker recipients, while the DX system addresses the population for cardioverter–defibrillator implantation. In the future, merging the two trunks of simplification—CRT via CSP and atrial lead omission through a DX system—could pave the way for a single-lead CRT-D system [34].

Limitations of the Study

The BIO|REDUCE study was designed as an observational investigation with a limited number of patients recruited during the COVID-19 pandemic. The study provides data for up to 12 months after CRT-DX implantation but lacks long-term follow-up results. Interpretation of the findings requires comparison with historical cohorts due to the absence of a control group. Despite these limitations, the study offers valuable insights into patient selection for CRT-DX systems and demonstrated CRT response rates that are comparable to those reported in previous studies with traditional CRT-D systems. The study provides a basis for a future randomized trial that directly compares CRT-DX with traditional three-lead CRT-D systems.

5. Conclusions

When clinically practical and simple inclusion criteria are used, the need for subsequent RA lead implantation in patients with two-lead CRT-DX systems (1.8%) may be lower than the RA lead complication rate observed in conventional three-lead CRT systems. Atrial sensing proved effective in maintaining reliable AV synchrony and achieving a high proportion of biventricular pacing. The two-lead CRT-DX concept may be a feasible alternative for patients with preserved chronotropic competence.

Author Contributions

Conceptualization, C.K., C.S., L.A., and A.F.; data curation, E.Z., M.F., H.B., T.D., B.S., T.S., B.M., and L.A.; formal analysis, C.K. and C.L.; funding acquisition, A.F.; investigation, C.K., E.Z., M.A., M.F., H.B., T.D., B.S., P.N., C.S., T.S., L.A., and C.L.; methodology, C.K. and A.F.; project administration, B.M. and A.F.; software, A.F.; supervision C.K.; validation M.A., M.F., H.B., T.D., B.S., P.N., B.M., L.A., A.F., and C.L.; visualization A.F. and C.L.; writing—original draft preparation, C.K. and A.F.; writing—review and editing, C.K., E.Z., M.A., M.F., H.B., T.D., B.S., P.N., C.S., T.S., B.M., L.A., A.F., and C.L. All authors have read and agreed to the published version of the manuscript.

Funding

This study (CR024) was supported by BIOTRONIK SE & Co. KG (Woermannkehre 1, D-12359 Berlin, Germany).

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki. The study protocol was approved by the responsible local ethics committees: Ethikkommission der Fakultät für Medizin der Technischen Universität München (25 January 2019; protocol code 523/18 S; the leading Ethics Committee in Germany), Ethikkommission der Medizinischen Fakultät der Johannes Kepler Universität Linz, Austria (18 February 2019; protocol code 1214/2018), Ethik-Kommission der Medizinischen Fakultät der Friedrich-Alexander-Universität Erlangen-Nürnberg (26 February 2019; protocol code 44_19 Bc), Ethik-Kommission der Medizinischen Fakultät der Christian-Albrechts-Universität zu Kiel (18 April 2019; protocol code B 231/19), Ethikkommission der Sächsischen Landesärztekammer (SLAEK) (3 May 2019; protocol code EK-BR-11/19-1/-2/-3), Semmelweis Egyetem Regionális, Intézményi Tudományos és Kutatásetikai Bizottság, Hungary (14 May 2019; protocol code 91/2019), Ethics Committee of the University Hospital Olomouc, Czech Republic (8 July 2019; protocol code 18/19), Etická komise Fakultní nemocnice Hradec Králové, Czech Republic (11 July 2019; protocol code 201907 D03ZP), Ethikkommission der Ärztekammer Nordrhein (30 July 2019; protocol code 2019181), Ethik-Kommission der Universität Würzburg (9 August 2019; protocol code 34/19), Ethikkommission an der Medizinischen Fakultät der Heinrich-Heine-Universität Düsseldorf (16 September 2019; protocol code 2629R), Ethikkommission der Landesärztekammer Rheinland-Pfalz (20 December 2019; protocol code 2019-14710), Ethikkommission an der Medizinischen Fakultät der Universität Rostock (18 May 2020; protocol code A2019-0025), Ethikkommission an der Technischen Universität Dresden (12 June 2020; protocol code BO-EK-169052020), and Ethikkommission Papenburg Aschendorf (18 June 2020; protocol code vM-krör). All patients provided written informed consent before enrollment.

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

The data underlying this article will be shared upon reasonable request to the corresponding author due to privacy reason.

Acknowledgments

We are profoundly grateful to Bernd Brüsehaber for performing the statistical analysis, Jürgen Schrader for discussions, and Dejan Danilovic for providing editorial support.

Conflicts of Interest

C.K. received lecture honoraria and travel support from Astra Zeneca, Biotronik, Bristol Myers Squibb, and Microport, and study compensation (to employer) from Abbott Medical, Biotronik, Boston Scientific, and Microport. E.Z. has no conflicts of interest to declare. M.A. has received speaker’s honoraria from Biotronik. M.F. has no conflicts of interest to declare. H.B. has no conflicts of interest to declare. T.D. has received educational grants from Biotronik. B.S. has no conflicts of interest to declare. P.N. has no conflicts of interest to declare. C.S. has no conflicts of interest to declare. T.S. has no conflicts of interest to declare. B.M. has no conflicts of interest to declare. L.A. has no conflicts of interest to declare. A.F. is an employee of Biotronik. C.L. has received lecture fees and travel support from Abbott, Biotronik, Boston Scientific, and Medtronic.

References

  1. Glikson, M.; Nielsen, J.C.; Kronborg, M.B.; Michowitz, Y.; Auricchio, A.; Barbash, I.M.; Barrabés, J.A.; Boriani, G.; Braunschweig, F.; Brignole, M.; et al. 2021 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy. Eur. Heart J. 2021, 42, 3427–3520, Erratum in: Eur. Heart J. 2022, 43, 1651. [Google Scholar] [CrossRef] [PubMed]
  2. McDonagh, T.A.; Metra, M.; Adamo, M.; Gardner, R.S.; Baumbach, A.; Böhm, M.; Burri, H.; Butler, J.; Čelutkienė, J.; Chioncel, O.; et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur. Heart J. 2021, 42, 3599–3726, Erratum in Eur. Heart J. 2021, 42, 4901. [Google Scholar] [CrossRef]
  3. Bristow, M.R.; Saxon, L.A.; Boehmer, J.; Krueger, S.; Kass, D.A.; De Marco, T.; Carson, P.; DiCarlo, L.; DeMets, D.; White, B.G.; et al. Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) Investigators. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N. Engl. J. Med. 2004, 350, 2140–2150. [Google Scholar] [CrossRef] [PubMed]
  4. Cleland, J.G.; Daubert, J.C.; Erdmann, E.; Freemantle, N.; Gras, D.; Kappenberger, L.; Tavazzi, L. Cardiac Resynchronization-Heart Failure (CARE-HF) Study Investigators. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N. Engl. J. Med. 2005, 352, 1539–1549. [Google Scholar] [CrossRef] [PubMed]
  5. Al-Majed, N.S.; McAlister, F.A.; Bakal, J.A.; Ezekowitz, J.A. Meta-analysis: Cardiac resynchronization therapy for patients with less symptomatic heart failure. Ann. Intern. Med. 2011, 154, 401–412. [Google Scholar] [CrossRef] [PubMed]
  6. Dewland, T.A.; Pellegrini, C.N.; Wang, Y.; Marcus, G.M.; Keung, E.; Varosy, P.D. Dual-chamber implantable cardioverter-defibrillator selection is associated with increased complication rates and mortality among patients enrolled in the NCDR implantable cardioverter-defibrillator registry. J. Am. Coll. Cardiol. 2011, 58, 1007–1013. [Google Scholar] [CrossRef] [PubMed]
  7. Peterson, P.N.; Varosy, P.D.; Heidenreich, P.A.; Wang, Y.; Dewland, T.A.; Curtis, J.P.; Go, A.S.; Greenlee, R.T.; Magid, D.J.; Normand, S.L.; et al. Association of single- vs. dual-chamber ICDs with mortality, readmissions, and complications among patients receiving an ICD for primary prevention. JAMA 2013, 309, 2025–2034. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  8. Sticherling, C.; Müller, D.; Schaer, B.A.; Krüger, S.; Kolb, C. Pre-CRAFT investigators. Atrial electrogram quality in single-pass defibrillator leads with floating atrial bipole in patients with permanent atrial fibrillation and cardiac resynchronization therapy. Indian Pacing Electrophysiol. J. 2018, 18, 140–145. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  9. Vamos, M.; Nemeth, M.; Balazs, T.; Zima, E.; Duray, G.Z. Rationale and feasibility of the atrioventricular single-lead ICD systems with a floating atrial dipole (DX) in clinical practice. Trends Cardiovasc. Med. 2022, 32, 84–89. [Google Scholar] [CrossRef] [PubMed]
  10. Biffi, M.; Massaro, G.; Candelora, A.; Angeletti, A.; Valzania, C.; Martignani, C.; Grassini, D.; Diemberger, I.; Ziacchi, M. Less is more: Can we achieve cardiac resynchronization with 2 leads only? Int. J. Cardiol. 2017, 249, 184–190. [Google Scholar] [CrossRef] [PubMed]
  11. Shaik, N.A.; Drucker, M.; Pierce, C.; Duray, G.Z.; Gillett, S.; Miller, C.; Harrell, C.; Thomas, G. Novel two-lead cardiac resynchronization therapy system provides equivalent CRT responses with less complications than a conventional three-lead system: Results from the QP ExCELs lead registry. J Cardiovasc. Electrophysiol. 2020, 31, 1784–1792. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  12. Brignole, M.; Auricchio, A.; Baron-Esquivias, G.; Bordachar, P.; Boriani, G.; Breithardt, O.A.; Cleland, J.; Deharo, J.C.; Delgado, V.; Elliott, P.M.; et al. 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: The Task Force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Eur. Heart J. 2013, 34, 2281–2329. [Google Scholar] [CrossRef] [PubMed]
  13. Ponikowski, P.; Voors, A.A.; Anker, S.D.; Bueno, H.; Cleland, J.G.F.; Coats, A.J.S.; Falk, V.; González-Juanatey, J.R.; Harjola, V.P.; Jankowska, E.A.; et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur. Heart J. 2016, 37, 2129–2200, Erratum in: Eur. Heart J. 2018, 39, 860. https://doi.org/10.1093/eurheartj/ehw383. [Google Scholar] [CrossRef] [PubMed]
  14. Bossard, M.; Sticherling, C.; Kühne, M.; Frey, S.; Osswald, S.; Schaer, B. Outcome of patients with cardiac resynchronisation defibrillator therapy and a follow-up of at least five years after implant. Swiss Med. Wkly. 2014, 144, w13938. [Google Scholar] [CrossRef] [PubMed]
  15. Adelstein, E.C.; Liu, J.; Jain, S.; Schwartzman, D.; Althouse, A.D.; Wang, N.C.; Gorcsan, J., 3rd; Saba, S. Clinical outcomes in cardiac resynchronization therapy-defibrillator recipients 80 years of age and older. Europace 2016, 18, 420–427. [Google Scholar] [CrossRef] [PubMed]
  16. Buber, J.; Klein, H.; Moss, A.J.; McNitt, S.; Eldar, M.; Padeletti, L.; Vogt, J.; Meine, M.; Brown, M.W.; Barsheshet, A.; et al. Clinical course and outcome of patients enrolled in US and non-US centres in MADIT-CRT. Eur. Heart J. 2011, 32, 2697–2704. [Google Scholar] [CrossRef] [PubMed]
  17. Ghani, A.; Delnoy, P.P.; Ramdat Misier, A.R.; Smit, J.J.; Adiyaman, A.; Ottervanger, J.P.; Elvan, A. Incidence of lead dislodgement, malfunction and perforation during the first year following device implantation. Neth. Heart J. 2014, 22, 286–291. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  18. Ruschitzka, F.; Abraham, W.T.; Singh, J.P.; Bax, J.J.; Borer, J.S.; Brugada, J.; Dickstein, K.; Ford, I.; Gorcsan, J., 3rd; Gras, D.; et al. Cardiac-resynchronization therapy in heart failure with a narrow QRS complex. N. Engl. J. Med. 2013, 369, 1395–1405. [Google Scholar] [CrossRef] [PubMed]
  19. Viechtbauer, W.; Smits, L.; Kotz, D.; Budé, L.; Spigt, M.; Serroyen, J.; Crutzen, R. A simple formula for the calculation of sample size in pilot studies. J. Clin. Epidemiol. 2015, 68, 1375–1379. [Google Scholar] [CrossRef] [PubMed]
  20. Kirkfeldt, R.E.; Johansen, J.B.; Nohr, E.A.; Moller, M.; Arnsbo, P.; Nielsen, J.C. Risk factors for lead complications in cardiac pacing: A population-based cohort study of 28,860 Danish patients. Heart Rhythm 2011, 8, 1622–1628. [Google Scholar] [CrossRef] [PubMed]
  21. León, A.R.; Abraham, W.T.; Curtis, A.B.; Daubert, J.P.; Fisher, W.G.; Gurley, J.; Hayes, D.L.; Lieberman, R.; Petersen-Stejskal, S.; Wheelan, K. MIRACLE Study Program. Safety of transvenous cardiac resynchronization system implantation in patients with chronic heart failure: Combined results of over 2000 patients from a multicenter study program. J. Am. Coll. Cardiol. 2005, 46, 2348–2356. [Google Scholar] [CrossRef] [PubMed]
  22. Palmisano, P.; Dell'Era, G.; Guerra, F.; Ammendola, E.; Ziacchi, M.; Laffi, M.; Donateo, P.; Guido, A.; Ghiglieno, C.; Parlavecchio, A.; et al. Complications of left bundle branch area pacing compared with biventricular pacing in candidates for resynchronization therapy: Results of a propensity score-matched analysis from a multicenter registry. Heart Rhythm 2024, 21, 874–880. [Google Scholar] [CrossRef] [PubMed]
  23. Van Rees, J.B.; de Bie, M.K.; Thijssen, J.; Borleffs, C.J.; Schalij, M.J.; van Erven, L. Implantation-related complications of implantable cardioverter-defibrillators and cardiac resynchronization therapy devices: A systematic review of randomized clinical trials. J. Am. Coll. Cardiol. 2011, 58, 995–1000. [Google Scholar] [CrossRef] [PubMed]
  24. Koplan, B.A.; Kaplan, A.J.; Weiner, S.; Jones, P.W.; Seth, M.; Christman, S.A. Heart failure decompensation and all-cause mortality in relation to percent biventricular pacing in patients with heart failure: Is a goal of 100% biventricular pacing necessary? J. Am. Coll. Cardiol. 2009, 53, 355–360. [Google Scholar] [CrossRef] [PubMed]
  25. Safak, E.; Schmitz, D.; Konorza, T.; Wende, C.; De Ros, J.O.; Schirdewan, A.; Linox, D.X. Study Investigators. Clinical efficacy and safety of an implantable cardioverter-defibrillator lead with a floating atrial sensing dipole. Pacing Clin. Electrophysiol. 2013, 36, 952–962. [Google Scholar] [CrossRef] [PubMed]
  26. Linde, C.; Abraham, W.T.; Gold, M.R.; St John Sutton, M.; Ghio, S.; Daubert, C. REVERSE (REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction) Study Group. Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms. J. Am. Coll. Cardiol. 2008, 52, 1834–1843. [Google Scholar] [CrossRef] [PubMed]
  27. Moss, A.J.; Hall, W.J.; Cannom, D.S.; Klein, H.; Brown, M.W.; Daubert, J.P.; Estes, N.A., 3rd; Foster, E.; Greenberg, H.; Higgins, S.L.; et al. Cardiac-resynchronization therapy for the prevention of heart-failure events. N. Engl. J. Med. 2009, 361, 1329–1338. [Google Scholar] [CrossRef] [PubMed]
  28. Burri, H.; Jastrzebski, M.; Cano, Ó.; Čurila, K.; de Pooter, J.; Huang, W.; Israel, C.; Joza, J.; Romero, J.; Vernooy, K.; et al. EHRA clinical consensus statement on conduction system pacing implantation: Endorsed by the Asia Pacific Heart Rhythm Society (APHRS), Canadian Heart Rhythm Society (CHRS), and Latin American Heart Rhythm Society (LAHRS). Europace 2023, 25, 1208–1236. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  29. Yousaf, A.; Ahmad, S.; Peltz, J.; Ahsan, M.J.; Abbas, K.S.; Muhammad, S.; Watson, C.; Asad, Z.U.A.; Kim, M.H. Left bundle branch area pacing vs biventricular pacing for cardiac resynchronization: A systematic review and meta-analysis. Heart Rhythm O2 2023, 4, 671–680. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  30. Lakshman, H.; Chowdhury, M.; Ahmed, A.; Woods, E.; Flemengos, G.; Abdou, C.; Patel, H.; Zughaib, M.; Bradley, C. Clinical and Electrophysiological Outcomes of Left Bundle Area Pacing Compared to Biventricular Pacing: An Updated Meta-analysis. J. Innov. Card. Rhythm. Manag. 2024, 15, 5858–5865. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  31. Wang, Y.; Zhu, H.; Hou, X.; Wang, Z.; Zou, F.; Qian, Z.; Wei, Y.; Wang, X.; Zhang, L.; Li, X.; et al. LBBP-RESYNC Investigators. Randomized Trial of Left Bundle Branch vs Biventricular Pacing for Cardiac Resynchronization Therapy. J. Am. Coll. Cardiol. 2022, 80, 1205–1216. [Google Scholar] [CrossRef] [PubMed]
  32. Pujol-Lopez, M.; Jiménez-Arjona, R.; Garre, P.; Guasch, E.; Borràs, R.; Doltra, A.; Ferró, E.; García-Ribas, C.; Niebla, M.; Carro, E.; et al. Conduction System Pacing vs Biventricular Pacing in Heart Failure and Wide QRS Patients: LEVEL-AT Trial. JACC Clin. Electrophysiol. 2022, 8, 1431–1445. [Google Scholar] [CrossRef] [PubMed]
  33. Ferreira Felix, I.; Collini, M.; Fonseca, R.; Guida, C.; Armaganijan, L.; Healey, J.S.; Carvalho, G. Conduction system pacing versus biventricular pacing in heart failure with reduced ejection fraction: A systematic review and meta-analysis of randomized controlled trials. Heart Rhythm 2024, 21, 881–889. [Google Scholar] [CrossRef] [PubMed]
  34. Varela, D.; Sandhu, A.; Zipse, M.; Aleong, R.G. Feasibility of Single-lead Cardiac Resynchronization and Defibrillation Therapy in an Animal Model. J. Innov. Card. Rhythm. Manag. 2024, 15, 5985–5989. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
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Figure 1. Daily mean RA sensing amplitude (blue graph) continuously documented by remote monitoring in 102 patients with CRT-DX configuration throughout the 12-month follow-up period. CRT-DX = cardiac resynchronization therapy defibrillator with atrial diagnostic dipole. RA = right atrial.
Figure 1. Daily mean RA sensing amplitude (blue graph) continuously documented by remote monitoring in 102 patients with CRT-DX configuration throughout the 12-month follow-up period. CRT-DX = cardiac resynchronization therapy defibrillator with atrial diagnostic dipole. RA = right atrial.
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Figure 2. Boxplot of LVEF values measured at baseline and after 12 months of CRT-DX therapy in 95 patients with paired data. The central line within each box represents the median, the box boundaries denote the interquartile range (IQR), whiskers extend to the smallest and largest values within 1.5 times the IQR from the quartiles, and circles represent the individual values outside the whiskers. CRT-DX = cardiac resynchronization therapy defibrillator with atrial diagnostic dipole, LVEF = left ventricular ejection fraction.
Figure 2. Boxplot of LVEF values measured at baseline and after 12 months of CRT-DX therapy in 95 patients with paired data. The central line within each box represents the median, the box boundaries denote the interquartile range (IQR), whiskers extend to the smallest and largest values within 1.5 times the IQR from the quartiles, and circles represent the individual values outside the whiskers. CRT-DX = cardiac resynchronization therapy defibrillator with atrial diagnostic dipole, LVEF = left ventricular ejection fraction.
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Figure 3. Sankey diagram for the change in NYHA functional class after 12 months of follow-up compared to baseline in 85 patients with paired data. Upward arrows indicate improvement (decrease) in the NYHA class. Downward arrows indicate worsening (increase) in the NYHA class. NYHA = New York Heart Association.
Figure 3. Sankey diagram for the change in NYHA functional class after 12 months of follow-up compared to baseline in 85 patients with paired data. Upward arrows indicate improvement (decrease) in the NYHA class. Downward arrows indicate worsening (increase) in the NYHA class. NYHA = New York Heart Association.
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Table 1. Patient characteristics at baseline.
Table 1. Patient characteristics at baseline.
CharacteristicValue (n = 110)
Age (years)62 ± 12
Male/female sex77/33 (70.0/30.0)
Primary prevention of sudden cardiac death97 (88.2)
Non-ischemic cardiomyopathy66 (60.0)
LVEF (%)26 ± 7
NYHA class
   I
   II
   III
   IV
0 (0)
60 (54.5)
50 (45.5)
0 (0)
Left bundle branch block103 (93.6)
Atrioventricular block
   None
   I°
   II°–III°
96 (87.3)
14 (12.7)
0 (0)
History of paroxysmal atrial fibrillation13 (11.8)
Heart rate at rest (bpm), n = 10969 ± 12
Maximum heart rate at exercise (bpm), n = 109116 ± 17
QRS duration (ms)161 ± 23
Concomitant diseases
   Diabetes mellitus
   Renal failure
   Hypertension
38 (34.5)
16 (14.5)
73 (66.4)
Medication
   Beta-blocker103 (93.6)
   ACE inhibitor/ARB/ARNI101 (91.8)
   Aldosterone antagonist90 (81.8)
   Diuretic69 (62.7)
   Glycoside3 (2.7)
Data are shown as mean ± standard deviation or n (%). ACE = angiotensin converting enzyme, ARB = angiotensin II receptor blocker, ARNI = angiotensin receptor/neprilysin inhibitor, bpm = beats/minute, LVEF = left ventricular ejection fraction, NYHA = New York Heart Association.
Table 2. Complication rates and mortality after 12 months of follow-up in 110 patients initially implanted with CRT-DX.
Table 2. Complication rates and mortality after 12 months of follow-up in 110 patients initially implanted with CRT-DX.
ComplicationPatients with Events, n (%)Events, nEvent-Free Rate for
Primary and Secondary Endpoints, % (95% CI)
Perforation0 (0)0
Pneumothorax with drainage3 (2.7)3
Post-operative system revision with invasive re-intervention11 (10.0)1189.9 (82.4–94.3) b
Lead complication with surgical re-intervention9 (8.2)991.7 (84.6–95.6) b
RA lead implantation after successful initial implantation of the CRT-DX system2 (1.8)298.2 (92.7–99.5) a
RV-DX lead dislodgment 2 (1.8)2
RV-DX lead threshold increase1 (0.9)1
LV lead dislodgment 3 (2.7)3
Pocket infection with CRT-DX explantation1 (0.9)199.1 (93.6–99.9) b
Wound healing disorder1 (0.9)1
CRT-DX repositioning due to pain/numbness 1 (0.9)1
All-cause mortality2 (1.8)2
Cardiovascular mortality0 (0)0
CI = confidence interval for event-free rates estimated using the Kaplan–Meier method, CRT-DX = cardiac resynchronization therapy defibrillator with atrial diagnostic dipole, LV = left ventricular, RA = right atrial, RV-DX = right ventricular lead with atrial sensing dipole and defibrillation coil. a referring to primary endpoint defined as an additional RA lead implantation, b referring to secondary endpoints defined as (i) any post-implant surgical re-intervention involving any component of the CRT-DX system, (ii) any lead complication, and (iii) device or pocket infection.
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Kolb, C.; Zima, E.; Arnold, M.; Fedorco, M.; Bonnemeier, H.; Deneke, T.; Schumacher, B.; Nordbeck, P.; Steinwender, C.; Storz, T.; et al. Biventricular Cardiac Resynchronization Therapy with Atrial Sensing but No Atrial Lead: A Prospective Registry of Patients, Complications, and Therapy Responses. J. Clin. Med. 2025, 14, 5009. https://doi.org/10.3390/jcm14145009

AMA Style

Kolb C, Zima E, Arnold M, Fedorco M, Bonnemeier H, Deneke T, Schumacher B, Nordbeck P, Steinwender C, Storz T, et al. Biventricular Cardiac Resynchronization Therapy with Atrial Sensing but No Atrial Lead: A Prospective Registry of Patients, Complications, and Therapy Responses. Journal of Clinical Medicine. 2025; 14(14):5009. https://doi.org/10.3390/jcm14145009

Chicago/Turabian Style

Kolb, Christof, Endre Zima, Martin Arnold, Marián Fedorco, Hendrik Bonnemeier, Thomas Deneke, Burghard Schumacher, Peter Nordbeck, Clemens Steinwender, Theresa Storz, and et al. 2025. "Biventricular Cardiac Resynchronization Therapy with Atrial Sensing but No Atrial Lead: A Prospective Registry of Patients, Complications, and Therapy Responses" Journal of Clinical Medicine 14, no. 14: 5009. https://doi.org/10.3390/jcm14145009

APA Style

Kolb, C., Zima, E., Arnold, M., Fedorco, M., Bonnemeier, H., Deneke, T., Schumacher, B., Nordbeck, P., Steinwender, C., Storz, T., Merkely, B., Anneken, L., Felk, A., & Lennerz, C., on behalf of the BIO|REDUCE Study Investigators. (2025). Biventricular Cardiac Resynchronization Therapy with Atrial Sensing but No Atrial Lead: A Prospective Registry of Patients, Complications, and Therapy Responses. Journal of Clinical Medicine, 14(14), 5009. https://doi.org/10.3390/jcm14145009

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