Cardiac Resynchronization Therapy Delivery Research Articles

Virtual pacing of a patient's digital twin to predict left ventricular reverse remodelling after cardiac resynchronization therapy.

Identifying heart failure (HF) patients who will benefit from cardiac resynchronization therapy (CRT) remains challenging. We evaluated whether virtual pacing in a digital twin (DT) of the patient's heart could be used to predict the degree of left ventricular (LV) reverse remodelling post-CRT. Forty-five HF patients with wide QRS complex (≥130 ms) and reduced LV ejection fraction (≤35%) receiving CRT were retrospectively enrolled. Echocardiography was performed before (baseline) and 6 months after CRT implantation to obtain LV volumes and 18-segment longitudinal strain. A previously developed algorithm was used to generate 45 DTs by personalizing the CircAdapt model to each patient's baseline measurements. From each DT, baseline septal-to-lateral myocardial work difference (MWLW-S,DT) and maximum rate of LV systolic pressure rise (dP/dtmax,DT) were derived. Biventricular pacing was then simulated using patient-specific atrioventricular delay and lead location. Virtual pacing-induced changes ΔMWLW-S,DT and ΔdP/dtmax,DT were correlated with real-world LV end-systolic volume change at 6-month follow-up (ΔLVESV). The DT's baseline MWLW-S,DT and virtual pacing-induced ΔMWLW-S,DT were both significantly associated with the real patient's reverse remodelling ΔLVESV (r = -0.60, P < 0.001 and r = 0.62, P < 0.001, respectively), while correlation between ΔdP/dtmax,DT and ΔLVESV was considerably weaker (r = -0.34, P = 0.02). Our results suggest that the reduction of septal-to-lateral work imbalance by virtual pacing in the DT can predict real-world post-CRT LV reverse remodelling. This DT approach could prove to be an additional tool in selecting HF patients for CRT and has the potential to provide valuable insights in optimization of CRT delivery.

Conduction System Pacing versus Conventional Biventricular Pacing for Cardiac Resynchronization Therapy: Where Are We Heading?

Over the last few years, pacing of the conduction system (CSP) has emerged as the new standard pacing modality for bradycardia indications, allowing a more physiological ventricular activation compared to conventional right ventricular pacing. CSP has also emerged as an alternative modality to conventional biventricular pacing for the delivery of cardiac resynchronization therapy (CRT) in heart failure patients. However, if the initial clinical data seem to support this new physiological-based approach to CRT, the lack of large randomized studies confirming these preliminary results prevents CSP from being used routinely in clinical practice. Furthermore, concerns are still present regarding the long-term performance of pacing leads when employed for CSP, as well as their extractability. In this review article, we provide the state-of-the-art of CSP as an alternative to biventricular pacing for CRT delivery in heart failure patients. In particular, we describe the physiological concepts supporting this approach and we discuss the future perspectives of CSP in this context according to the implant techniques (His bundle pacing and left bundle branch area pacing) and the clinical data published so far.

Improved prognosis after cardiac resynchronization therapy over a decade.

The past decade has seen an increased delivery of cardiac resynchronization therapy (CRT) for patients with heart failure (HF). We explored whether clinical outcomes after CRT have changed from the perspective of an entire public healthcare system. A national database covering the population of England (56.3 million in 2019) was used to explore clinical outcomes after CRT from 2010 to 2019. A total of 64 698 consecutive patients (age 71.4 ± 11.7 years; 74.8% male) underwent CRT-defibrillation [n = 32 313 (49.7%)] or CRT-pacing [n = 32 655 (50.3%)] implantation. From 2010-2011 to 2018-2019, there was a 76% increase in CRT implantations. During the same period, the proportion of patients with hypertension (59.6-73.4%), diabetes (26.5-30.8%), and chronic kidney disease (8.62-22.5%) increased, as did the Charlson comorbidity index (CCI ≥ 3 from 20.0% to 25.1%) (all P < 0.001). Total mortality decreased at 30 days (1.43-1.09%) and 1 year (9.51-8.13%) after implantation (both P < 0.001). At 2 years, total mortality [hazard ratio (HR): 0.72; 95% confidence interval (CI) 0.69-0.76] and total mortality or HF hospitalization (HR: 0.59; 95% CI 0.57-0.62) decreased from 2010-2011 to 2018-2019, after correction for age, race, sex, device type (CRT-defibrillation or pacing), comorbidities (hypertension, diabetes, chronic kidney disease, and myocardial infarction), or the CCI (HR: 0.81; 95% CI 0.77-0.85). From the perspective of an entire public health system, survival has improved and HF hospitalizations have decreased after CRT implantation over the past decade. This prognostic improvement has occurred despite an increasing comorbidity burden.

Comparison of immediate changes of repolarization parameters after left bundle branch area pacing and traditional biventricular pacing in heart failure patients.

Comparison of immediate changes of repolarization parameters after left bundle branch area pacing and traditional biventricular pacing in heart failure patients.

Comparison between conduction system pacing and cardiac resynchronization therapy in right bundle branch block patients.

A significant number of right bundle branch block (RBBB) patients receive cardiac resynchronization therapy (CRT), despite lack of evidence for benefit in this patient group. His bundle (HBP) and left bundle pacing (LBP) are novel CRT delivery methods, but their effect on RBBB remains understudied. We aim to compare pacing-induced electrical synchrony during conventional CRT, HBP, and LBP in RBBB patients with different conduction disturbances, and to investigate whether alternative ways of delivering LBP improve response to pacing. We simulated ventricular activation on twenty-four four-chamber heart geometries each including a His-Purkinje system with proximal right bundle branch block (RBBB). We simulated RBBB combined with left anterior and posterior fascicular blocks (LAFB and LPFB). Additionally, RBBB was simulated in the presence of slow conduction velocity (CV) in the myocardium, left ventricular (LV) or right ventricular (RV) His-Purkinje system, and whole His-Purkinje system. Electrical synchrony was measured by the shortest interval to activate 90% of the ventricles (BIVAT-90). Compared to baseline, HBP significantly improved activation times for RBBB alone (BIVAT-90: 66.9 ± 5.5 ms vs. 42.6 ± 3.8 ms, p < 0.01), with LAFB (69.5 ± 5.0 ms vs. 58.1 ± 6.2 ms, p < 0.01), with LPFB (81.8 ± 6.6 ms vs. 62.9 ± 6.2 ms, p < 0.01), with slow myocardial CV (119.4 ± 11.4 ms vs. 97.2 ± 10.0 ms, p < 0.01) or slow CV in the whole His-Purkinje system (102.3 ± 7.0 ms vs. 75.5 ± 5.2 ms, p < 0.01). LBP was only effective in RBBB cases if combined with anodal capture of the RV septum myocardium (BIVAT-90: 66.9 ± 5.5 ms vs. 48.2 ± 5.2 ms, p < 0.01). CRT significantly reduced activation times in RBBB in the presence of severely slow RV His-Purkinje CV (95.1 ± 7.9 ms vs. 84.3 ± 9.3 ms, p < 0.01) and LPFB (81.8 ± 6.6 ms vs. CRT: 72.9 ± 8.6 ms, p < 0.01). Both CRT and HBP were ineffective with severely slow CV in the LV His-Purkinje system. HBP is effective in RBBB patients with otherwise healthy myocardium and Purkinje system, while CRT and LBP are ineffective. Response to LBP improves when LBP is combined with RV septum anodal capture. CRT is better than HBP only in patients with severely slow CV in the RV His-Purkinje system, while CV slowing of the whole His-Purkinje system and the myocardium favor HBP over CRT.

Status and Update on Cardiac Resynchronization Therapy Trials.

After decades of clinical use, cardiac resynchronization therapy (CRT) can be considered an established therapy. However, there are multiple open questions to be addressed that shall further improve the proportion of patients responding to CRT. Progress in better understanding the relationship between electrical and mechanical disorder in patients with heart failure with ventricular conduction abnormalities is important. This article presents and discusses ongoing studies in different areas of CRT research, including patient selection by novel diagnostic tools, extension of clinical criteria, left ventricular lead positioning and pacing site selection, optimization of CRT delivery and programming, and selection of device type.

Multi-lead pacing for cardiac resynchronization therapy in heart failure: a meta-analysis of randomized controlled trials.

AimsMulti-lead pacing is a potential therapy to improve response to cardiac resynchronization therapy (CRT) by providing rapid activation of the myocardium from multiple sites. Here, we perform a meta-analysis of randomized controlled trials to assess the efficacy of multi-lead pacing.Methods and resultsA literature search was performed which identified 251 unique records. After screening, 6 studies were found to meet inclusion criteria, with 415 patients included in the meta-analysis. Four studies performed multi-lead pacing with two left ventricular (LV) leads and one right ventricular (RV) lead. One study used two RV leads and one LV lead, and one study used both configurations. There was no difference between multi-lead pacing and conventional CRT in LV end-systolic volume [mean difference (MD) −0.54 mL, P = 0.93] or LV ejection fraction (MD 1.42%, P = 0.40). There was a borderline significant improvement in Minnesota Living With Heart Failure Questionnaire score for multi-lead pacing vs. conventional CRT (MD −4.46, P = 0.05), but the difference was not significant when only patients receiving LV-only multi-lead pacing were included (MD −3.59, P = 0.25). There was also no difference between groups for 6-min walk test (MD 15.06 m, P = 0.38) or New York Heart Association class at follow-up [odds ratio (OR) 1.49, P = 0.24]. There was no difference in mortality between groups (OR 1.11, P = 0.77).ConclusionThis meta-analysis does not support the use of multi-lead pacing for CRT delivery. However, significant variation between studies was noted, and therefore a benefit for multi-lead pacing in select patients cannot be excluded, and further investigation may be warranted.

Left atrial strain is a predictor of left ventricular systolic and diastolic reverse remodelling in CRT candidates

The left atrium (LA) has a pivotal role in cardiac performance and LA deformation is a well-known prognostic predictor in several clinical conditions including heart failure with reduced ejection fraction. The aim of this study is to investigate the effect of cardiac resynchronization therapy (CRT) on both LA morphology and function and to assess the impact of LA reservoir strain (LARS) on left ventricular (LV) systolic and diastolic remodelling after CRT. Two hundred and twenty-one CRT-candidates were prospectively included in the study in four tertiary centres and underwent echocardiography before CRT-implantation and at 6-month follow-up (FU). CRT-response was defined by a 15% reduction in LV end-systolic volume. LV systolic and diastolic remodelling were defined as the percent reduction in LV end-systolic and end-diastolic volume at FU. Indexed LA volume (LAVI) and LV-global longitudinal (GLS) strain were the main parameters correlated with LARS, with LV-GLS being the strongest determinant of LARS (r = -0.59, P < 0.0001). CRT induced a significant improvement in LAVI and LARS in responders (both P < 0.0001). LARS was an independent predictor of both LV systolic and diastolic remodelling at follow-up (r = -0.14, P = 0.049 and r = -0.17, P = 0.002, respectively). CRT induces a significant improvement in LAVI and LARS in responders. In CRT candidates, the evaluation of LARS before CRT delivery is an independent predictor of LV systolic and diastolic remodelling at FU.

Fine-tuning delivery of cardiac resynchronization therapy: Optimization for “triple fusion”

Maximizing efficacy and avoiding nonresponse are important aims of cardiac resynchronization therapy (CRT) delivery. Current recommendations emphasize careful candidate selection and left ventricle (LV) lead delivery but do not extend to postimplant optimization in the absence of convincing benefit. However, optimizing electrical resynchronization depends on the interaction between patient substrate and paced effects and may need individualization. Recent data indicate that “Triple Fusion” optimizes CRT delivery.

Left ventricle pacing challenges in cardiac resynchronization therapy systems.

Left ventricle (LV) pacing can be considered peculiar due to its different lead/tissue interface (epicardial pacing) and the small vein wedging lead locations with less reliable lead stability. The current technologies available for LV capture automatic confirmation adopt the evoked response (ER), as well as “LV pace to right ventricular (RV) sense” algorithms. The occurrence of anodal RV capture is today completely solved by the use of bipolar LV leads, while intriguing data are recently published regarding the unintentional LV anodal capture beside the cathodal one, which may enlarge the front wave of cardiac resynchronization therapy (CRT) delivery. The LV threshold behavior over time leading to ineffective CRT issues (subthreshold stimulation or concealed loss of capture), the extracardiac capture with phrenic nerve stimulation (PNS), the flexible electronic cathode reprogramming and the inadequate CRT delivery related to inadequate AV and VV pace timing (and its management by LV “dromotropic pace-conditioning”) are discussed.Moreover, recently, His bundle pacing (HBP) and left bundle branch pacing (LBBP) have shown growing interest to prevent pacing-induced cardiomyopathy as well as for direct intentional CRT.The purpose of the present review is to explore these new challenges regarding LV pacing starting from old concepts.

European experience with a first totally leadless cardiac resynchronization therapy pacemaker system.

AimsTotally leadless cardiac resynchronization therapy (CRT) can be delivered with a combination of Micra and WiSE-CRT systems. We describe the technical feasibility and first insights into the safety and efficacy of this combination in European experience.Methods and resultsPatients enrolled had indication for both Micra and WiSE-CRT systems because of heart failure related to high burden of pacing by a Micra necessitating system upgrade or inability to implant a conventional CRT system because of infectious or anatomical conditions. The endpoints of the study were technical success of WiSE-CRT implantation with right ventricle-synchonized CRT delivery, acute QRS duration reduction, and freedom from procedure-related major adverse events. All eight WiSE-CRT devices were able to detect the Micra pacing output and to be trained to deliver synchronous LV endocardial pacing. Acute QRS reduction following WiSE-CRT implantation was observed in all eight patients (mean QRS 204.38 ± 30.26 vs. 137.5 ± 24.75 mS, P = 0.012). Seven patients reached 6 months of follow-up. At 6 months after WiSE-CRT implantation, there was a significant increase in LV ejection fraction (28.43 ± 8.01% vs. 39.71 ± 11.89%; P = 0.018) but no evidence of LV reverse remodelling or improvement in New York Heart Association class.ConclusionThe Micra and the WiSE-CRT systems can successfully operate together to deliver total leadless CRT to a patient. Moreover, the WiSE-CRT system provides the only means to upgrade the large population of Micra patients to CRT capability without replacing the Micra. The range of application of this combination could broaden in the future with the upcoming developments of leadless cardiac pacing.

Left ventricle automatic pacing threshold management in CRT systems: A comprehensive review.

Modern cardiac resynchronization therapy (CRT) device-based threshold detection enables capture management and voltage output adjusting to combine consistent left ventricular (LV) pacing with acceptable battery drainage. The current technologies available for LV capture automatic confirmation in most cases require the evoked response, as well as "LV pace to right ventricular sense" algorithms.The LV pacing percentage counter may overestimate the CRT delivery which may be reduced due to pacing inhibition (by sensed LV activation) or inadequate capture due to subthreshold current or pacing into refractory tissue. Moreover, the LV threshold at implant and its behavior over time (as a marker of electrical viability) and the ineffective CRT issues (subthreshold stimulation or concealed loss of capture) are discussed.The purpose of the present review is to explore these new challenges regarding LV pacing automatic management.

Left bundle branch area pacing delivery of cardiac resynchronization therapy and comparison with biventricular pacing.

AimsThis multicentre observational study aimed to prospectively assess the efficacy of left bundle branch area pacing (LBBAP) in heart failure patients with left bundle branch block (LBBB) and compare the 6‐month outcomes between LBBAP and biventricular pacing (BVP).Methods and resultsConsecutive patients with LBBB and left ventricular ejection fraction (LVEF) ≤ 35% were prospectively recruited if they had undergone LBBAP as a primary or rescue strategy from three separate centres from March to December 2018. Patients who received BVP in 2018 were retrospectively selected by using 2 to 1 propensity score matching to minimize bias. Implant characteristics and echocardiographic parameters were assessed during the 6‐month follow‐up. LBBAP procedure succeeded in 81.1% (30/37) of patients, with selective LBBAP in 10 patients, and 3 of 20 patients combined non‐selective LBBAP and LV lead pacing for further QRS narrowing. LBBAP resulted in significant QRS narrowing (from 178.2 ± 18.8 to 121.8 ± 10.8 ms, P < 0.001, paced QRS duration ≤ 130 ms in 27 patients) and improved LVEF (from 28.8 ± 4.5% to 44.3 ± 8.7%, P < 0.001) during the 6‐month follow‐up. The comparison between 27 patients with LBBAP alone and 54 of 130 matching patients with BVP showed that LBBAP delivered a greater reduction in the QRSd (58.0 vs. 12.5 ms, P < 0.001), a greater increase in LVEF (15.6% vs. 7.0%, P < 0.001), and greater echocardiographic (88.9% vs. 66.7%, P = 0.035) and super response (44.4% vs. 16.7%, P = 0.007) to cardiac resynchronization therapy.ConclusionsLBBAP could deliver cardiac resynchronization therapy in most patients with heart failure and LBBB, and might be a promising alternative resynchronization approach to BVP.

Left ventricular sensing in cardiac resynchronization devices-opportunities and pitfalls for device programming.

Some cardiac resynchronization therapy (CRT) device manufacturers (Biotronik, Germany; Boston Scientific, United States) have implemented left ventricular (LV) sensing functionality to prevent pacing into the vulnerable phase. Physicians are only partially aware of programming pitfalls related to LV sensing and general programming advice is lacking. We provide an illustrative case-series-based review of the variety of potential problems with LV sensing. LV sensing may inappropriately impair CRT delivery due to LV-sensing issues or improper device programming. This can cause beat-wise loss of resynchronization but also ongoing desynchronization. On the other hand, LV sensing provides additional diagnostic information, which may reveal intermittent problems of the LV lead such as capture loss. We summarize the available evidence to provide manufacturer-specific recommendations on device programming and troubleshooting for daily clinical practice. CRT devices with LV sensing may suffer from impaired resynchronization due to programming pitfalls. If LV sensing is active (nominal setting in Biotronik and Boston Scientific devices), careful lookout for related problems and resynchronization percentage is required. Optimization is mandatory and even deactivation of LV sensing may have to be considered.

Utility of Novel Vectors in a Quadripolar Left Ventricular Lead

Background Two complications which frequently arise with the use of cardiac resynchronization therapy (CRT) are phrenic nerve stimulation (PNS) and/or high pacing thresholds. These complications often result in costly and invasive surgical procedures required to revise an existing left ventricular (LV) lead in order to provide safe and optimal therapy. Quadripolar (QP) left ventricular leads include four electrically active rings which provide redundancy and allow the prescriber to change pacing configurations and optimize CRT delivery. This capability can also be used to resolve PNS or high pacing threshold by programming a new pacing vector, and thus provides a low-risk alternative to traditional invasive procedures. Objective The goal of this study is to evaluate the utility of seven programmable novel LV pacing vectors which utilize one or both distal rings that are unique to quadripolar LV leads. Methods The analysis was part of a multi-center, prospective, non-randomized study. Novel pacing vector data was collected during a clinic follow-up visit at 3 months post implant for subjects implanted with a BIOTRONIK Sentus QP lead in combination with a BIOTRONIK CRT-D implantable device. Novel vectors contained one or both distal LV rings (LV3 and LV4) and were evaluated via a threshold test at a pulse width of 0.4 ms. LV pacing thresholds ≤ 2.5 V at 0.4 ms were considered acceptable. Results A total of 930 subjects were successfully implanted at 76 U.S. and international sites. Of 662 subjects with available novel data at 3 months post implant, there were 509 subjects who underwent threshold testing of at least four of the seven novel pacing vectors. The percentage of subjects in this group with at least one novel vector with an acceptable LV pacing threshold was 89.2% (N=454). Table 1 provides the number and percentage of subjects for the total novel vectors with an acceptable threshold. Conclusion The results demonstrate an ability to provide alternate novel vector pacing configurations for subjects who may otherwise require an invasive procedure to resolve PNS or high pacing threshold.

Avances tecnológicos para mejorar la respuesta ventricular en la resincronización cardiaca: lo que el clínico debe conocer

Cardiac resynchronization therapy (CRT) is a well-established treatment for symptomatic heart failure patients with reduced left ventricular ejection fraction, prolonged QRS duration, and abnormal QRS morphology. The ultimate goals of modern CRT are to improve the proportion of patients responding to CRT and to maximize the response to CRT in patients who do respond. While the rate of CRT nonresponders has moderately but progressively decreased over the last 20 years, mostly in patients with left bundle branch block, in patients without left bundle branch block the response rate is almost unchanged. A number of technological advances have already contributed to achieve some of the objectives of modern CRT. They include novel lead design (the left ventricular quadripolar lead, and multipoint pacing), or the possibility to go beyond conventional delivery of CRT (left ventricular endocardial pacing, His bundle pacing). Furthermore, to improve CRT response, a triad of actions is paramount: reducing the burden of atrial fibrillation, reducing the number of appropriate and inappropriate interventions, and adequately predicting heart failure episodes. As in other fields of cardiology, technology and innovations for CRT delivery have been at the forefront in transforming—improving—patient care; therefore, these innovations are discussed in this review.

Technology Advances to Improve Response to Cardiac Resynchronization Therapy: What Clinicians Should Know

Cardiac resynchronization therapy (CRT) is a well-established treatment for symptomatic heart failure patients with reduced left ventricular ejection fraction, prolonged QRS duration, and abnormal QRS morphology. The ultimate goals of modern CRT are to improve the proportion of patients responding to CRT and to maximize the response to CRT in patients who do respond. While the rate of CRT nonresponders has moderately but progressively decreased over the last 20 years, mostly in patients with left bundle branch block, in patients without left bundle branch block the response rate is almost unchanged. A number of technological advances have already contributed to achieve some of the objectives of modern CRT. They include novel lead design (the left ventricular quadripolar lead, and multipoint pacing), or the possibility to go beyond conventional delivery of CRT (left ventricular endocardial pacing, His bundle pacing). Furthermore, to improve CRT response, a triad of actions is paramount: reducing the burden of atrial fibrillation, reducing the number of appropriate and inappropriate interventions, and adequately predicting heart failure episodes. As in other fields of cardiology, technology and innovations for CRT delivery have been at the forefront in transforming–improving–patient care; therefore, these innovations are discussed in this review.

Atrial fibrillation and cardiac resynchronization therapy.

Atrial fibrillation and heart failure are commonly encountered in current clinical practice. This review aims to revisit the complex interaction of these two common situations and the best treatment whenever both occurs, especially focusing on heart failure patients undergoing cardiac resynchronization therapy (CRT). It has been recently confirmed that in patients undergoing cardiac resynchronization therapy, 100% biventricular pacing percentage should be pursued. Large observational studies confirmed that atrioventricular junction ablation is very often the only way to gain 100% biventricular pacing in atrial fibrillation. On the basis of the recent observational extensive data, in patients presenting intermediate or elevated atrial tachycardia-atrial fibrillation burden, atrioventricular junction ablation may represent a fundamental tool to achieve full CRT delivery, thus, conferring marked improvements in global cardiac function, and by extension, in survival. Atrial fibrillation patients should not be excluded from CRT, provided that maximal biventricular pacing is warranted.

A novel algorithm increases the delivery of effective cardiac resynchronization therapy during atrial fibrillation: The CRTee randomized crossover trial

Cardiac resynchronization therapy (CRT) requires a high percentage of ventricular pacing (%Vp) to maximize its clinical benefits. Atrial fibrillation (AF) has been shown to reduce %Vp in CRT due to competition with irregular intrinsic atrioventricular (AV) conduction. We report the results of a prospective randomized crossover trial evaluating the amount of effective CRT delivered during AF with a novel algorithm (eCRTAF). The purpose of this study was to determine whether eCRTAF increases the amount of effective CRT delivered during AF compared to a currently available rate regularization algorithm. Patients previously implanted with a cardiac resynchronization therapy-defibrillator and with a history of AF and intact AV conduction received up to 4 weeks of control (Conducted AF Response) and up to 4 weeks of eCRTAF in a randomized sequence. The percent effective CRT (%eCRT) pacing, which excludes beats without left ventricular capture, %Vp, and mean heart rate (HR) were recorded during AF and sinus rhythm. The eCRTAF algorithm resulted in a significantly higher %eCRT during AF than control (87.8% ± 7.8% vs 80.8% ± 14.3%; P<.001) and %Vp during AF than control (90.0% ± 5.9% vs 83.2% ± 11.9%; P <.001), with a small but statistically significant increase in mean HR of 2.5 bpm (79.5 ± 9.7 bpm vs 77.0 ± 9.9 bpm; P <.001). In a cohort of CRT patients with a history of AF, eCRTAF significantly increased %eCRT pacing and %Vp during AF with a small increase in mean HR. This algorithm may represent a novel noninvasive method of significantly increasing effective CRT delivery during AF, potentially improving CRT response.

Real-Time X-MRI-Guided Left Ventricular Lead Implantation for Targeted Delivery ofCardiac Resynchronization Therapy.

This study sought to test the feasibility of a purpose-built, integrated software platform to process, analyze, and overlay cardiac magnetic resonance (CMR) data in real time within a combined cardiac catheter laboratory and magnetic resonance imaging scanner suite (X-MRI) to guide left ventricular (LV) lead implantation. Suboptimal LV lead position is a major determinant of poor cardiac resynchronization therapy (CRT) response, and the optimal site is highly patient specific. Pacing myocardial scar is associated with poorer outcomes; conversely, targeting latest mechanical activation (LMA) may improve them. Fourteen patients (age 74 ± 5.1 years; New York Heart Association functional class: 2.7 ± 0.4; 86% ischemic with ejection fraction 27 ± 7.6%; QRSd: 157 ± 19 ms) underwent CMR followed by immediate CRT implantation using derived scar and dyssynchrony data, overlaid onto fluoroscopy in an X-MRI suite. Rapid LV segmentation enabled detailed scar quantification, identification of LMA segments, and selection of myocardial targets. At coronary venography, the CMR-derived 3-dimensional shell was fused, enabling identification of viable venous targets subtended by target segments for LV lead placement. The platform was successful in all 14 patients, of whom 10 (71%) were paced in pre-procedurally defined target segments. Pacing in CMR-defined target segments (out of scar) showed a significant decrease in the LV capture threshold (mean difference: 2.4 [1.5 to 3.2]; p< 0.001) and shorter paced QRS duration (mean difference: 25 [15 to 34]; p< 0.001) compared with pacing in areas of CMR determined scar. In 5 (36%) patients with extensive scar in the posterolateral wall, CMR guidance enabled successful lead delivery in an alternative anatomically favorable site. Radiation dose and implant times were similar to historical controls (p= NS). Real-time CMR-guided LV lead placement is feasible and achievable in a single clinical setting andmayprove helpful to preferentially select sites for LV lead placement.