Investigating the clinical utility of global and regional myocardial work parameters in predicting response to cardiac resynchronization therapy in patients with heart failure and reduced ejection fraction.

Background: Previous studies have indicated that despite adhering to current patient selection guidelines, there remains a 30% to 40% subset of patients who do not experience improvement in heart failure (HF) after receiving cardiac resynchronization therapy (CRT). We aim to utilize echocardiographic myocardial work parameters to serve as predictors of responsiveness to CRT in patients with heart failure and reduced ejection fraction (HFrEF). Methods: We prospectively recruited patients who underwent CRT at Sun Yat-sen Memorial Hospital from June 2019 to September 2022. Comprehensive preoperative information, clinical laboratory data, conventional echocardiographic parameters and myocardial work were collected for all participants, as well as follow-up data 6 months after CRT. Results: Twenty-five patients (67.6%) showed response to CRT treatment, while twelve patients (32.4%) had no response. Compared with the non-response group, the response group had larger region constructive work [RCW: the sum of constructive work (CW) in the 9 segments of the basal, mid, and apical segments of the anterior, lateral, and posterior walls], region wasted work [RWW: the sum of wasted work (WW) in the 6 segments of the basal and mid segments of the anterior septum, posterior septum and anterior walls], and the combination of RCW and RWW (RCW + RWW) in baseline (RCW: 9,695.68±2,955.40 vs. 5,219.50±2,207.68 mmHg%, P<0.001; RWW: 3,612.08±1,723.80 vs. 1,674.33±995.23 mmHg%, P=0.001; RCW + RWW: 13,307.76±3,857.71 vs. 6,893.83±2,592.83 mmHg%, P<0.001). Furthermore, global constructive work (GCW), global wasted work (GWW), GCW + GWW, RCW, RWW, and RCW + RWW had areas under the receiver operating characteristic curve (AUCs) of 0.870, 0.770, 0.860, 0.890, 0.870, and 0.910, respectively, for predicting CRT responsiveness. Conclusions: The global and regional myocardial work parameters are associated with CRT response in CRT candidates. Particularly regional myocardial work parameters appear to be promising parameters to improve selection for CRT of patients with HFrEF.

Conduction time from left bundle branch pacing to the left ventricular lateral wall in two patients in whom cardiac resynchronization therapy pacemaker was implanted.

The efficacy of left bundle branch pacing (LBBP) as cardiac resynchronization therapy (CRT) has been reported, but LBBP may not always improve conduction disturbance in the left ventricle (LV). To evaluate LV electrical conduction delay during LBBP, we measured conduction time from the pacing at left bundle branch to LV lead sensing (LBBP-LV) in two patients in whom left bundle branch-optimized cardiac resynchronization therapy (LOT-CRT) was attempted. Case 1 was a 77-year-old female with dilated cardiomyopathy (DCM) and left bundle branch block. The QRS duration during LBBP was 160 ms and the interval between the stimulus artifact and peak of the R wave in lead V6 (Stim-V6RWPT) was 74 ms. LBBP-LV at the LV mid-lateral wall and LV mid-posterolateral wall were 112 ms and 102 ms, respectively. Case 2 was a 75-year-old female with DCM and nonspecific intraventricular conduction delay. The QRS duration during LBBP was 156 ms and Stim-V6RWPT was 66 ms. LBBP-LV at the LV mid-anterolateral wall, LV mid-lateral wall, and LV mid-posterolateral wall were 96 ms, 107 ms, and 121 ms, respectively. In conclusion, LBBP-LV at the LV mid-lateral area was relatively long. If LBBP does not improve LV conduction disturbances, LOT-CRT may be more effective. Learning objective: The efficacy of left bundle branch pacing (LBBP) for cardiac resynchronization therapy (CRT) has been reported. However, if the conduction time from pacing to the left ventricular (LV) lateral area during LBBP is long, LBBP may not improve LV conduction disturbance, resulting in ineffective CRT. In such cases, more effective CRT would be expected with LV lead implantation at the area of the LV conduction delay during LBBP.

Emergent role of dynamic optimization in cardiac resynchronization therapy: Systematic review and network meta-analysis.

AIMS: Suboptimal device programming is frequent in non-responders to cardiac resynchronization therapy (CRT). However, the role of device optimization and the most appropriate technique are still unknown. The aim of our study was to analyse the effect of different CRT optimization techniques within a network meta-analysis. METHODS: A systematic search was conducted on MEDLINE, Embase and CENTRAL for studies comparing outcomes with empirical device settings or optimization using echocardiography, static algorithms or dynamic algorithms. Studies investigating the effect of optimization in non-responders were also analysed. RESULTS: A total of 17 studies with 4346 patients were included in the quantitative analysis. Of the treatments and outcomes examined, a significant difference was found only between dynamic algorithms and echocardiography, with the former leading to a higher echocardiographic response rate [odds ratio (OR): 2.02, 95% confidence interval (CI) 1.21-3.35], lower heart failure hospitalization rate (OR: 0.75, 95% CI 0.57-0.99) and greater improvement in 6-minute walk test [mean difference (MD): 45.52 m, 95% credible interval (CrI) 3.91-82.44 m]. We found no significant difference between empirical settings, static algorithms and dynamic algorithms. Seven studies with 228 patients reported response rates after optimization in non-responders. Altogether, 34.3%-66.7% of initial non-responders showed improvement after optimization, depending on response criteria. CONCLUSIONS: At the time of CRT implantation, dynamic algorithms may serve as a resource-friendly alternative to echocardiographic optimization, with similar or better mid-term outcomes. However, their superiority over empirical device settings needs to be investigated in further trials. For non-responders, CRT optimization should be considered, as the majority of patients experience improvement.

A Novel Liver Fibrosis Marker FIB-5 Index Predicted Response to Cardiac Resynchronization Therapy and Prognostic Outcomes in Patients With Heart Failure.

BACKGROUND: The fibrosis-5 (FIB-5) index is a noninvasive marker for assessing the progression of liver fibrosis and predictor in patients with heart failure (HF). This study investigated the association between the FIB-5 index and response to cardiac resynchronization therapy (CRT) and evaluated its predictive value for prognosis. METHODS: In total, 203 patients who underwent CRT/CRT-defibrillator (CRT-D) implantation were retrospectively included. The FIB-5 index was calculated using blood samples obtained before and after CRT/CRT-D. Response to CRT was defined as a relative reduction in left ventricular end-systolic volume of ≥15% 6 months after CRT/CRT-D. We compared the prognosis after CRT/CRT-D between the groups according to the FIB-5 index. RESULTS: One hundred and twenty-three patients (61%) responded to CRT. The responder group demonstrated a significantly higher FIB-5 index than the nonresponder group (-2.76 ± 3.85 vs. -4.67 ± 3.29, p < 0.001). Receiver-operating characteristic analysis demonstrated that the area under the curve of the FIB-5 index was 0.660 with a cutoff value of -4.00 for responders. In multivariate analysis, FIB-5 index ≥ -4.00 was an independent predictor for CRT response (odds ratio: 3.665, p = 0.003), in addition to QRS duration ≥ 150 ms and echocardiographic dysynchrony. The FIB-5 index increased significantly after 6 months in the responder group but not in the nonresponder group. The FIB-5 index ≥ -4.00 group showed a significantly better prognosis for cardiac death, HF hospitalization, and composite endpoint than the FIB-5 index < -4.00 group. CONCLUSION: The FIB-5 index in addition to classical predictors may be a useful marker for predicting response to CRT.

Contralateral transvenous left ventricular lead placement of an implantable device with pre-sternal tunneling in an ipsilateral chronically obstructed subclavian vein.

Multiple methods are used to tackle ipsilateral obstructed venous access in patients undergoing a device upgrade by implanting a new left ventricular lead. One feasible solution to tackle this is implantation of the upgrade lead contralaterally with pre-sternal tunnelization to the opposite side under conscious sedation.

Vitamin D as a predictor of clinical response among patients with cardiac resynchronization therapy (CRT).

Introduction: Cardiovascular and noncardiovascular comorbidities have been recognized as predictors of clinical response in patients receiving cardiac resynchronization therapy (CRT). However, data on vitamin D as a predictor of CRT response are conflicting. Method: We identified studies from MEDLINE and Embase databases, searching from inception to May 2024, to investigate the association between 25-OH vitamin D levels before CRT implantation and outcomes. Studies had to report 25-OH vitamin D levels or the proportion of patients with vitamin D insufficiency and categorize outcomes as CRT responders or nonresponders. We extracted mean 25-OH vitamin D and standard deviations for both groups from each study and calculated the pooled mean difference (MD). We also retrieved risk ratios, and 95% confidence intervals (CIs) for the association between vitamin D insufficiency and lack of CRT response, combining them using the generic inverse variance method. Results: Our meta-analysis included four studies. CRT responders had higher levels of 25-OH vitamin D than nonresponders, with a pooled MD of 8.04 ng/mL (95% CI: 3.16-12.93; I 2 = 48%, p < .001). Patients with vitamin D insufficiency before implantation had higher odds of lacking response to CRT, with a pooled RR of 3.28 (95% CI: 1.43-7.50; I 2 = 0%, p = .005) compared to those with normal vitamin D. Conclusions: CRT responders had higher 25-OH vitamin D levels compared to nonresponders. Vitamin D insufficiency was associated with a higher risk of nonresponse to CRT. These findings highlight the importance of monitoring and managing vitamin D levels in these patients.

Assessment of the correlation between Doppler derived dP/dt and aortic velocity-time integral during cardiac resynchronization therapy optimization.

PURPOSE: Suboptimal response to cardiac resynchronization therapy (CRT) may be improved by optimization of device parameters using echocardiography. For this purpose, the aortic velocity-time integral (aVTI) has been used as a target metric to define optimal velocity timings for each ventricle. dP/dt is a parameter used for the assessment of myocardial contractility. In this study, we aimed to evaluate the effectiveness of Doppler-derived dP/dt in optimization by assessing the possible correlation between aVTI and dP/dt. METHODS: Patients with CRT admitted for routine follow-up were included in the study. Aortic VTI and dP/dt measurements were recorded in four different standard pacing configurations during reprogramming. RESULTS: A total of 45 patients were included in the final analysis. No correlation was found between the aVTI and the delta dP/dt value in the two configurations where the change in dP/dt was maximum (p = 0.894). In the two configurations where the change in aVTI was maximum, there was also no correlation between the delta dP/dt and the delta aVTI (p = 0.715). When patients were dichotomized according to the median value of dP/dt, there were no differences in aVTI, NYHA classes, LVEF, and mitral regurgitation (MR) severity (p = 0.4; p = 0.5; p = 0.7; p = 0.3; respectively). The change in both dP/dt and aVTI was statistically significant when switching from RV-only to QRS width-targeted configuration (p = 0.001; p = 0.041; respectively). CONCLUSION: In conclusion, aVTI recorded at different pacing configurations did not correlate with dP/dt during interventricular optimization. However, both parameters consistently showed a positive effect of biventricular pacing on contractile synchronization and stroke volume.

Conduction system pacing upgrade versus biventricular pacing on pacemaker-induced cardiomyopathy: a retrospective observational study.

Objective: The feasibility of the conduction system pacing (CSP) upgrade as an alternative modality to the traditional biventricular pacing (BiVP) upgrade in patients with pacemaker-induced cardiomyopathy (PICM) remains uncertain. This study sought to compare two modalities of CSP (His bundle pacing (HBP) and left bundle branch pacing (LBBP)) with BiVP and no upgrades in patients with pacing-induced cardiomyopathy. Methods: This retrospective analysis comprised consecutive patients who underwent either BiVP or CSP upgrade for PICM at the cardiac department from 2017 to 2021. Patients with a follow-up period exceeding 12 months were considered for the final analysis. Results: The final group of patients who underwent upgrades included 48 individuals: 11 with BiVP upgrades, 24 with HBP upgrades, and 13 with LBBP upgrades. Compared to the baseline data, there were significant improvements in cardiac performance at the last follow-up. After the upgrade, the QRS duration (127.81 ± 31.89 vs 177.08 ± 34.35 ms, p < 0.001), NYHA class (2.28 ± 0.70 vs 3.04 ± 0.54, p < 0.05), left ventricular end-diastolic diameter (LVEDD) (54.08 ± 4.80 vs 57.50 ± 4.85 mm, p < 0.05), and left ventricular ejection fraction (LVEF) (44.46% ± 6.39% vs 33.15% ± 5.25%, p < 0.001) were improved. There was a noticeable improvement in LVEF in the CSP group (32.15% ± 3.22% vs 44.95% ± 3.99% (p < 0.001)) and the BiVP group (33.90% ± 3.09% vs 40.83% ± 2.99% (p < 0.001)). The changes in QRS duration were more evident in CSP than in BiVP (56.65 ± 11.71 vs 34.67 ± 13.32, p < 0.001). Similarly, the changes in LVEF (12.8 ± 3.66 vs 6.93 ± 3.04, p < 0.001) and LVEDD (5.80 ± 1.71 vs 3.16 ± 1.35, p < 0.001) were greater in CSP than in BiVP. The changes in LVEDD (p = 0.549) and LVEF (p = 0.570) were similar in the LBBP and HBP groups. The threshold in LBBP was also lower than that in HBP (1.01 ± 0.43 vs 1.33 ± 0.32 V, p = 0.019). Conclusion: The improvement of clinical outcomes in CSP was more significant than in BiVP. CSP may be an alternative therapy to CRT for patients with PICM. LBBP would be a better choice than HBP due to its lower thresholds.

Clinical Usefulness of the Active Fixation Quadripolar Left Ventricular Lead Compared With the Passive Fixation Quadripolar Lead in Cardiac Resynchronization Therapy.

BACKGROUND: This study compared the stability of the Medtronic Attain Stability Quad (ASQ), a novel quadripolar active fixation left ventricular (LV) lead with a side helix, to that of conventional quadripolar leads with passive fixation (non-ASQ) and evaluated their LV lead performance.Methods and Results: In all, 183 consecutive patients (69 ASQ, 114 non-ASQ) who underwent cardiac resynchronization therapy (CRT) between January 2018 and June 2021 were enrolled. Complications, including elevated pacing capture threshold (PCT) levels, phrenic nerve stimulation (PNS), and LV lead dislodgement, were analyzed during the postimplantation period until the first outpatient visit after discharge. The frequency of LV lead-related complications was significantly lower in the ASQ than non-ASQ group (14% vs. 30%, respectively; P=0.019). Specifically, LV lead dislodgement occurred only in the non-ASQ group, and elevated PCT levels were significantly lower in the ASQ group (7% vs. 23%; P=0.007). Kaplan-Meier analysis confirmed a significantly lower incidence of LV lead-related complications in the ASQ group (log-rank P=0.005). Cox multivariable regression analysis showed a significant reduction in lead-related complications associated with ASQ (hazard ratio 0.44; 95% confidence interval 0.23-0.83; P=0.011). CONCLUSIONS: The ASQ group exhibited fewer LV lead-related complications requiring reintervention and setting changes than the non-ASQ group. Thus, the ASQ may be a favorable choice for CRT device implantation.

Mechanical dyssynchrony as a selection criterion for cardiac resynchronization therapy: Design of the AMEND-CRT trial.

AIMS: One third of patients do not improve after cardiac resynchronization therapy (CRT). Septal flash (SF) and apical rocking (ApRock) are deformation patterns observed on echocardiography in most patients eligible for CRT. These markers of mechanical dyssynchrony have been associated to improved outcome after CRT in observational studies and may be useful to better select patients. The aim of this trial is to investigate whether the current guideline criteria for selecting patients for CRT should be modified and include SF and ApRock to improve therapy success rate, reduce excessive costs and prevent exposure to device-related complications in patients who would not benefit from CRT. METHODS: The AMEND-CRT trial is a multicentre, randomized, parallel-group, double-blind, sham-controlled trial with a non-inferiority design. The trial will include 578 patients scheduled for CRT according to the 2021 ESC guidelines who satisfy all inclusion criteria. The randomization is performed 1:1 to an active control arm ('guideline arm') or an experimental arm ('echo arm'). All participants receive a device, but in the echo arm, CRT is activated only when SF or ApRock or both are present. The outcome of both arms will be compared after 1 year. The primary outcome measures are the average change in left ventricular end-systolic volume and patient outcome assessed using a modified Packer Clinical Composite Score. CONCLUSIONS: The findings of this trial will redefine the role of echocardiography in CRT and potentially determine which patients with heart failure and a prolonged QRS duration should receive CRT, especially in patients who currently have a class IIa or class IIb recommendation.

Deactivation of cardiac implantable electronic devices in palliative patients: When and how.

Cardiac implantable electronic devices have transformed medicine as they improve quality of life and prevent premature death. In palliative care settings, deactivation of these devices must be discussed, particularly at end-of-life. In terminally ill patients it is consensual to recommend implantable cardioverter defibrillator deactivation once shocks are frequent and painful. Concerning pacemakers, the decision to deactivate is controversial and it usually is not an option at patients' end-of-life, since in pacing-dependent patients, such low heart rates might induce symptoms of bradycardia, with no impact on survival. Regarding cardiac resynchronization therapy, deactivation is not recommended as it can worsen symptoms. Left ventricular assistance device deactivation at end-of-life is a well-accepted practice, since it has the benefit of ending the physical burden associated with the device. Advance care planning should be encouraged and patients should be informed that deactivation is possible.

Association between echocardiography-derived haemodynamic force parameters and left ventricular reverse remodelling after cardiac resynchronization therapy.

AIMS: Cardiac resynchronization therapy (CRT) may induce left ventricular (LV) reverse remodelling (=LV response) in patients with heart failure. Intraventricular pressure gradients can be quantified using echocardiography-derived haemodynamic forces (HDF). The aim was to evaluate the association between baseline HDF and LV response and to compare the change of HDF after CRT between LV responders and LV non-responders. METHODS AND RESULTS: The following HDF parameters were assessed: 1)apical-basal (AB) strength, 2)lateral-septal strength, 3)force vector angle, 4)systolic AB impulse, 5)systolic force vector angle. LV response was defined as a reduction of LV end-systolic volume ≥15% at six months. One hundred ninety-six patients were included (64±11 years, 122(62%) men), 136(69%) showed LV response. On multivariable logistic regression analysis, the force vector angle in the complete heart cycle (OR 1.083 (95%CI 1.018, 1.153), p=0.012) and the systolic force vector angle (OR 1.089 (95%CI 1.021, 1.161), p=0.009), both included in separate models, were independently associated with LV response. Six months after CRT, LV responders had greater AB strength, AB impulse and higher force vector angles, while LV non-responders only showed improvement in the force vector angle in the complete heart cycle. CONCLUSION: The orientation of HDF at baseline is associated with LV response to CRT. Six months after CRT, the orientation of HDF improves in LV responders and LV non-responders, while the magnitude of AB HDF only improves in LV responders.

Feasibility, safety, and short-term follow-up of defibrillator lead at left bundle branch area pacing location: A pilot study.

BACKGROUND: Left bundle branch area pacing (LBBAP) has been increasingly adopted as an alternative modality to cardiac resynchronization therapy (CRT). The feasibility and safety of using an LBBAP lead to provide sensing of ventricular arrhythmia in patients receiving an implantable cardioverter-defibrillator (ICD) with CRT has been demonstrated recently. OBJECTIVES: The purpose of our study was to analyze the feasibility, safety, and short-term follow-up of a traditional defibrillator lead at the LBBAP location. METHODS: Patients who underwent successful LBBAP defibrillator using DF-1/DF-4 lead and delivery catheter were included in the study. Defibrillation threshold (DFT) testing was performed after implantation to assess the ability of the LBBAP defibrillator lead to sense and provide appropriate therapy for ventricular arrhythmia. RESULTS: Although the ICD lead could be successfully deployed in the left bundle branch area in 7 of 8 patients, it was repositioned to the right ventricular (RV) apex because of atrial oversensing in 1 patient and cheesy septum in another patient. Acute procedural success was 62.5% (5/8 patients). Mean patient age was 62.6 ± 21.6 years. Mean procedural duration was 115.6 ± 38.1 minutes, with LBBAP defibrillator lead fluoroscopy duration of 10.6 ± 3.5 minutes. Mean capture threshold was 0.58 ± 0.23V/0.4 ms, sensed R-wave amplitude 9.6 ± 2.2 mV, pacing impedance 560 ± 145 Ω, and shock impedance 65.4 ± 5.5 Ω. Defibrillation testing was successful in inducing ventricular fibrillation and could be sensed and reverted promptly by the shock delivered through the lead. During mean follow-up of 3.8 ± 2.2 months, pacing parameters remained stable. No episodes of inappropriate arrhythmia detection or therapy delivery occurred during follow-up. CONCLUSION: LBBAP defibrillator is feasible, safe, and effective during short-term follow-up. DFT testing at the time of implantation will help to ensure appropriate sensing and treatment of ventricular arrhythmias.

Performance of the quadripolar CRT-D system: Five-year results from the Quadripolar Pacing Post-Approval Study.

BACKGROUND: Cardiac resynchronization therapy (CRT) is associated with challenges such as elevated capture thresholds, diaphragmatic stimulation, and lead instability. OBJECTIVE: This study aimed to assess the long-term safety and efficacy of the quadripolar CRT-defibrillator (CRT-D) device system with the Quartet 1458Q left ventricular (LV) lead in a CRT-indicated population observed for 5 years and to evaluate all-cause mortality and impact of baseline characteristics on survival through 5 years. METHODS: Patients indicated for a CRT-D system were observed every 6 months after implantation for 5 years, and device performance and adverse events were assessed at each visit. The 3 primary end points were freedom from quadripolar CRT-D system-related complications through 5 years, freedom from Quartet 1458Q LV lead-related complications through 5 years, and mean programmed pacing capture threshold at 5 years. RESULTS: The study enrolled 1970 participants at 71 sites. The quadripolar CRT-D system was successfully implanted in 97.2% of participants. Freedom from quadripolar CRT-D device system-related complications through 5 years was 89.7%. Freedom from Quartet 1458Q LV lead-related complications through 5 years was 95.7%; 3.49% of participants had LV lead-related complications, and an overall LV lead complication rate was 0.0122 event per patient-year. The mean LV pacing capture threshold was 1.52 ± 1.01 V at 5 years. The 5-year survival rate was 67.4%. CONCLUSION: The quadripolar CRT-D system with the Quartet 1458Q LV lead exhibited low rates of complications and stable electrical performance through 5 years of follow-up and suggested a higher 5-year survival rate compared with traditional CRT systems.

LV cathode position in CRT recipients: How can we benefit from CMR?

BACKGROUND: Left ventricular lead positioning represents a key step in CRT optimization. However, evidence for its guidance based on specific topographical factors and related imaging techniques is sparse. OBJECTIVE: To analyze reverse remodeling (RR) and clinical events in CRT recipients based on LV cathode (LVC) position relative to latest mechanical activation (LMA) and scar as determined by cardiac magnetic resonance (CMR). METHODS: This is a retrospective single-center study of 68 consecutive Q-LV-guided CRT-D and CRT-P recipients. Through CMR-based 3D reconstructions overlayed on fluoroscopy images, LVCs were stratified as concordant, adjacent, or discordant to LMA (3 segments with latest and greatest radial strain) and scar (segments with >50% scar transmurality). The primary endpoint of RR (expressed as percentage ESV change) and secondary composite endpoint of HF hospitalizations, LVAD/heart transplant, or cardiovascular death were compared across categories. RESULTS: LVC proximity to LMA was associated with a progressive increase in RR (percentage ESV change: concordant -47.0 ± 5.9%, adjacent -31.4 ± 3.1%, discordant +0.4 ± 3.7%), while proximity to scar was associated with sharply decreasing RR (concordant +10.7 ± 12.9%, adjacent +0.3 ± 5.3%, discordant -31.3 ± 4.4%, no scar -35.4 ± 4.8%). 4 integrated classes of LVC position demonstrated a significant positive RR gradient the more optimal the category (class I -47.0 ± 5.9%, class II -34.9 ± 2.8%, class III -5.5 ± 4.3%, class IV + 3.4 ± 5.2%). Freedom from composite secondary endpoint of HF hospitalization, LVAD/heart transplant, or cardiovascular death confirmed these trends demonstrating significant differences across both integrated as well as individual LMA and scar categories. CONCLUSION: Integrated CMR-determined LVC position relative to LMA and scar stratifies response to CRT.

Conduction System Pacing: Hope, Challenges, and the Journey Forward.

PURPOSE OF THE REVIEW: Cardiac pacing has evolved in recent years currently culminating in the specific stimulation of the cardiac conduction system (conduction system pacing, CSP). This review aims to provide a comprehensive overview of the available literature on CSP, focusing on a critical classification of studies comparing CSP with standard treatment in the two fields of pacing for bradycardia and cardiac resynchronization therapy in patients with heart failure. The article will also elaborate specific benefits and limitations associated with CSP modalities of His bundle pacing (HBP) and left bundle branch area pacing (LBBAP). RECENT FINDINGS: Based on a growing number of observational studies for different indications of pacing therapy, both CSP modalities investigated are advantageous over standard treatment in terms of narrowing the paced QRS complex and preserving or improving left ventricular systolic function. Less consistent evidence exists with regard to the improvement of heart failure-related rehospitalization rates or mortality, and effect sizes vary between HBP and LBBAP. LBBAP is superior over HBP in terms of lead measurements and procedural duration. With regard to all reported outcomes, evidence from large scale randomized controlled clinical trials (RCT) is still scarce. CSP has the potential to sustainably improve patient care in cardiac pacing therapy if patients are appropriately selected and limitations are considered. With this review, we offer not only a summary of existing data, but also an outlook on probable future developments in the field, as well as a detailed summary of upcoming RCTs that provide insights into how the journey of CSP continues.