Optimization of left ventricular lead implantation based on combined myocardial perfusion scintigraphy and computed tomography data

Anna I. Mishkina; Мишкина Анна Ивановна; Anna I. Mishkina; Tariel A. Atabekov; Атабеков Тариель Абдилазимович; Tariel A. Atabekov; Svetlana I. Sazonova; Сазонова Светлана Ивановна; Svetlana I. Sazonova; Roman E. Batalov; Баталов Роман Ефимович; Roman E. Batalov; Sergey V. Popov; Попов Сергей Валентинович; Sergey V. Popov; Konstantin V. Zavadovsky; Завадовский Константин Валерьевич; Konstantin V. Zavadovsky

doi:10.17816/DD635333

Optimization of left ventricular lead implantation based on combined myocardial perfusion scintigraphy and computed tomography data

Authors: Mishkina A.I.¹, Atabekov T.A.¹, Sazonova S.I.¹, Batalov R.E.¹, Popov S.V.¹, Zavadovsky K.V.¹
Affiliations:
1. Tomsk National Research Medical Centre, Russian Academy of Sciences
Issue: Vol 6, No 2 (2025)
Pages: 229-238
Section: Original Study Articles
Submitted: 22.08.2024
Accepted: 25.09.2024
Published: 08.07.2025
URL: https://jdigitaldiagnostics.com/DD/article/view/635333
DOI: https://doi.org/10.17816/DD635333
EDN: https://elibrary.ru/JPGZLU
ID: 635333

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Abstract

BACKGROUND: Successful cardiac resynchronization therapy in patients with chronic heart failure critically depends on the selection of the optimal implantation site for the left ventricular lead. A hybrid imaging approach combining cardiac venous computed tomography and myocardial perfusion scintigraphy may assist in identifying the target vein and improve procedural efficacy.

AIM: The work aimed to evaluate the feasibility of a multimodal imaging approach for optimizing left ventricular lead implantation in cardiac resynchronization therapy.

METHODS: It was a prospective, observational, single-center, non-randomized controlled study. Patients with chronic heart failure and indications for cardiac resynchronization therapy in accordance with current guidelines were enrolled. Prior to the procedure, the patients underwent computed tomography of the cardiac veins to visualize venous anatomy and myocardial perfusion scintigraphy to assess the extent of left ventricular perfusion impairment. The optimal site for left ventricular lead placement was identified using a three-dimensional reconstruction of the coronary sinus fused with myocardial perfusion scintigraphy data. To assess the effectiveness of the hybrid approach, a reference group was formed, in which cardiac resynchronization implantation was performed using the standard method, without preprocedural evaluation of coronary venous anatomy or myocardial scarring. Six months after cardiac resynchronization therapy, all patients underwent echocardiography to evaluate treatment effectiveness. Echocardiographic response was defined as a reduction in left ventricular end-systolic volume by ≥15% and/or an increase in ejection fraction by ≥5%.

RESULTS: The imaging group consisted of 40 patients with chronic heart failure, whereas the reference group included 30 patients with the same diagnosis. Six months after cardiac resynchronization therapy, a positive treatment response was observed in 33 patients (82%) in the imaging group, significantly higher than in the reference group (17 patients, 57%), p = 0.031. In the imaging group, the reduction in left ventricular end-systolic volume was statistically significant compared with the reference group and amounted to −52 [−71; −22.5] mL versus −21 [−64; −1] mL, respectively (p = 0.039). The increase in left ventricular ejection fraction was 7.5 [4.5; 15]% in the imaging group and 4.5 [0; 13]% in the reference group, with no statistically significant difference (p = 0.082).

CONCLUSION: The use of cardiovascular imaging methods, including cardiac venous computed tomography and myocardial perfusion scintigraphy, was associated with an increased proportion of responders to cardiac resynchronization therapy.

Keywords

cardiac venous computed tomography, myocardial perfusion scintigraphy, chronic heart failure, cardiac resynchronization therapy

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BACKGROUND

Chronic heart failure (CHF) remains one of the major challenges in modern cardiology. Despite advances in treatment, the prognosis of patients with CHF of New York Heart Association (NYHA) functional classes II–III remains unfavorable [1, 2]. Pharmacological therapy does not always provide adequate symptom control or improve prognosis in this group. Therefore, increasing attention has been directed toward interventional methods, including implantation of cardiac devices [3].

Cardiac resynchronization therapy (CRT) is an effective treatment option for patients with CHF with reduced left ventricular ejection fraction (LVEF) and ventricular conduction abnormalities. This treatment modality is aimed at synchronizing ventricular electrical activity, leading to the restoration of contractile function and a reduction in CHF functional class. It also decreases the rate of hospitalizations due to decompensation and improves survival [4]. At the same time, 40% of cases do not demonstrate a positive response to CRT [5, 6]. One of the primary approaches to increasing its effectiveness is the optimization of patient selection for device implantation [7, 8].

To address this issue, cardiovascular imaging methods are widely used [9–11] because of their high accuracy in identifying potential responders¹ to CRT [12]. Recent studies show that the effectiveness of CRT in patients with ischemic cardiomyopathy is lower than in those with non-ischemic forms of the disease [13]. Furthermore, the presence of extensive scar tissue in the region where the left ventricular lead is placed is associated with a lack of response to CRT [14]. Therefore, at the planning stage of the interventional procedure, it is important to determine the localization of myocardial scar tissue to guide the selection of an optimal implantation site [14]. One method that can address this need is myocardial perfusion scintigraphy (MPS), which provides simultaneous assessment of myocardial perfusion and LV contractile function. However, due to variability in coronary venous anatomy, it is not always possible during the procedure to identify a target vein for lead implantation that corresponds to a region of myocardium with preserved perfusion. This necessitates preliminary noninvasive imaging of the coronary venous system using computed tomography (CT venography) [15]. We hypothesized that a hybrid imaging approach, specifically the combination of CT venography and MPS data, would allow for optimization of target vein selection for LV lead implantation during CRT, thereby improving the effectiveness of the interventional procedure.

AIM

The work aimed to evaluate the potential of a multimodal imaging approach for optimizing LV lead implantation during CRT.

METHODS

Study Design

An observational, single-center, prospective, nonrandomized, controlled study was conducted.

Eligibility Criteria

Inclusion criteria:

patients with CHF of NYHA functional class II and III of ischemic and nonischemic etiology eligible for CRT according to current guidelines [4];
reduced LVEF ≤ 35% according to echocardiography (Echo);
QRS duration > 130 ms;
complete left bundle branch block.

Exclusion criteria:

acute myocardial infarction;
coronary artery bypass grafting or coronary artery stenting within the previous 3 months;
unstable angina;
acute myocarditis;
severe primary stenosis or regurgitation of the mitral, tricuspid, or aortic valve;
mental or physical inability to participate in the study;
severe chronic kidney disease (estimated glomerular filtration rate
< 30 mL/min/1.73 m².

Study Setting

The study included patients hospitalized for an interventional procedure in the Department of Surgical Treatment of Complex Cardiac Arrhythmias and Cardiac Pacing at the Research Institute of Cardiology, Tomsk National Research Medical Center (NRMC). Scintigraphic examinations were performed at the Shared Research Equipment Facility “Medical Genomics,” Tomsk NRMC.

Study Duration

The study was conducted from May 2020 to February 2024. All patients included in the study were rehospitalized 6 months after the interventional procedure to assess treatment effectiveness.

Intervention

MPS was performed at rest with intravenous administration of the radiopharmaceutical technetium-^99m methoxyisobutylisonitrile (^99mTc-MIBI) at a dose of 370–450 MBq. Scintigraphic images were acquired in ECG-gated mode (16 frames per cardiac cycle) 90 minutes after the radiopharmaceutical injection. The data acquisition duration was 10 minutes. The obtained images were processed using specialized software to generate a normalized 17-segment polar map of the LV reflecting myocardial perfusion (Fig. 1).

Fig. 1. Results of left ventricular myocardial perfusion scintigraphy in a patient with chronic heart failure: short- and long-axis slices and a 17-segment polar map of the left ventricle (the arrow indicates a perfusion defect involving the apex, anterior, and anteroseptal regions). SA, short axis; HLA, horizontal long axis; VLA, vertical long axis; INF, inferior wall; ANT, anterior wall; SEP, septal wall; LAT, lateral wall; REST_IRAC, Rest Integrated Regional Activity Counts; SRS, summed rest score.

Cardiac CT venography was performed using a multislice computed tomography scanner with intravenous administration of 90–110 mL of the nonionic iodinated contrast agent iopromide 370 mg/mL through a cubital vein catheter. When necessary, a beta-blocker was administered to maintain a heart rate below 70 beats per minute. Image acquisition was performed with ECG gating in retrospective mode. Scanning was initiated at the moment of dense contrast opacification of the descending aorta at the level of the coronary sinus, using a technical delay of 6 seconds. From the acquired CT venography data, a 3D model of the heart and coronary veins was reconstructed (Fig. 2a) using the Advantage Workstation VolumeShare® platform (GE Healthcare, United States). Based on this model, the anatomy of the cardiac veins was evaluated. Subsequently, the 3D reconstruction of the coronary veins was fused with the MPS images (see Fig. 2b). Based on the combined data, the coronary sinus vein for left ventricular lead placement was selected. A vein was considered a target if it corresponded to a region without hypoperfusion (radiopharmaceutical uptake > 50%). LV segments with radiopharmaceutical uptake < 50% (Summed Rest Score, SRS > 2 points) were excluded from consideration as implantation sites.

Fig. 2. 3D reconstruction of the heart and coronary sinus: a, model based on computed tomography data; b, fusion of coronary vein computed tomography data with perfusion scintigraphy results of the left ventricular myocardium.

The total effective radiation dose from both examinations was approximately 8.33 mSv.

Patients in both groups underwent implantation of a cardiac resynchronization device with defibrillator capability according to the standard methodology for biventricular cardiac pacing. The device was programmed in accordance with international standards [16].

Main Study Outcome

The primary endpoint was the response to CRT 6 months after the intervention as assessed by Echo. Criteria for a positive response included a reduction in LV end systolic volume (ESV) and/or an increase in LVEF by ≥ 15% and ≥ 5%, respectively.

Additional Study Outcomes

The secondary endpoint was the occurrence of an adverse cardiovascular event: major adverse cardiovascular events (MACE), cardiovascular death, or hospitalization due to CHF decompensation.

Subgroup Analysis

The first group—the imaging group—was recruited prospectively. All patients in this group underwent a set of imaging examinations before CRT, including cardiac CT venography with contrast enhancement to assess anatomical features of the coronary veins and MPS to evaluate LV myocardial perfusion.

The comparison group was recruited retrospectively. Patients in this group underwent implantation of a resynchronization device according to the standard technique without preoperative assessment of coronary venous anatomy or scar tissue.

Outcomes Registration

Outcomes were evaluated using Echo 6 months after the interventional procedure.

Ethics Approval

The study was approved by the Biomedical Ethics Committee of the Research Institute of Cardiology, Tomsk NRMC (minutes No. 232, dated October 26, 2022).

All participants provided written informed consent to participate in the study before enrollment.

Statistical Analysis

Principles for sample size calculation. The sample size was not pre-calculated.

Statistical data analysis methods. Statistical analysis was performed using MedCalc® 12.1.14.0 (MedCalc Software Ltd, Belgium) and STATISTICA® 10.0 (StatSoft Inc., USA). Quantitative variables are presented as Me [Q1; Q3], where Me is the median and Q1 and Q3 are the 1st and 3rd quartiles, respectively. Normally distributed quantitative variables are presented as M ± SD, where M is the the mean value and SD is standard deviation. Categorical variables are presented as absolute (n) and relative (%) frequencies. The statistical significance of intergroup differences in quantitative variables was assessed using the nonparametric Mann–Whitney U test. Categorical variables were compared using the Fisher exact test. Differences were considered statistically significant at p < 0.05.

RESULTS

Participants

The clinical and demographic characteristics of the patients and the Echo data in both groups are presented in Table 1. The groups did not differ statistically in clinical characteristics or LV volume and contractility according to Echo.

Table 1. Clinical and demographic characteristics of patients in the imaging and comparison groups

Parameter	Imaging group (n = 40)	Comparison group (n = 30)	p-value
Sex (men/women), n	26/14	16/14	0.338
Age, years	59.5 [55; 68]	58 [48; 64]	0.183
Heart failure: NYHA functional class II/III, n	22/18	11/19	0.224
Etiology of chronic heart failure (ischemic/non-ischemic), n	15/25	10/20	0.804
QRS duration, ms	171 [160; 184]	166 [160; 180]	0.284
Diabetes mellitus, n (%)	5 (12)	3 (10)	0.712
Body mass index	28.4 [24.3; 31.1]	30.2 [25; 32.2]	0.446
Left ventricular end-diastolic volume, mL	240 [210; 283]	226 [190; 54]	0.202
Left ventricular end-systolic volume, mL	181 [146; 203]	161 [125; 195]	0.306
Left ventricular ejection fraction, %	30 [25; 32]	29 [21; 32]	0.711
Note. Data are presented as Me [Q1; Q3], where Me is the median and Q1 and Q3 are the 1st and 3rd quartiles, respectively; NYHA, New York Heart Association.

Primary Results

In the imaging group, the left ventricular lead was implanted in the target vein selected based on the 3D reconstruction of the coronary sinus fused with MPS data. In the comparison group, the lead was placed using the standard technique without imaging guidance. The frequency of using various coronary veins as the target vein is shown in Table 2. Statistically significant differences were observed between the groups regarding the frequency of selecting the lateral vein as the target vein for left ventricular lead placement (p = 0.015); in other cases, no significant differences were found.

Table 2. Frequency of different target veins used for left ventricular lead implantation in the groups

Target vein	Imaging group, n (%)	Comparison group, n (%)
Lateral vein	24 (60)	8 (27)
Posterolateral vein	10 (25)	14 (47)
Anterolateral vein	4 (10)	6 (20)
Posterior vein of the left ventricle	2 (5)	2 (6)

To assess the influence of the imaging approach on the procedure, fluoroscopy dose and fluoroscopy time during the procedure were analyzed. No statistically significant differences were identified between the groups for these parameters (Table 3). However, the radiation dose received by patients in the imaging group due to additional preoperative imaging studies should be taken into account [the mean effective dose for the entire diagnostic protocol was 8.2 ± 0.8 mSv (range, 7.6–9.1) per patient].

Table 3. Comparison of fluoroscopy dose and time during the procedure in the imaging and comparison groups

Parameter	Imaging group	Comparison group	p-value
Effective radiation dose, mSv	0,96 [0, 52; 2]	1,5 [0, 82; 2, 1]	0,082
Fluoroscopy time, min	15,5 [10; 18]	15 [10; 17]	0,832
Note. Data are presented as Me [Q1; Q3], where Me, median; Q1 and Q3, the 1st and 3rd quartiles, respectively.

Six months after the interventional procedure, statistically significant differences in the frequency of achieving the primary endpoint were observed (p = 0.031):

33 patients (82%) in the imaging group;
17 patients (57%) in the comparison group.

No secondary endpoints occurred in either group.

A comparative analysis of changes in LV volume and contractility after CRT in the study groups is presented in Table 4.

Table 4. Comparative characteristics of changes in left ventricular volume and contractility after cardiac resynchronization therapy in the imaging and comparison groups

Parameter	Imaging group	Comparison group	p-value
Δ Left ventricular end-systolic volume, mL	−52 [−71; −22,5]	−21 [−64; −1]	0,039¹
Δ Left ventricular ejection fraction, %	7,5 [4, 5; 15]	4,5 [0; 13]	0,082
Note. Data are presented as Me [Q1; Q3], where Me, median; Q1 and Q3, the 1st and 3rd quartiles, respectively. ¹Statistically significant differences between the groups.

DISCUSSION

Summary of Primary Results

The findings of this study indicate that a comprehensive imaging approach—including CT venography of the heart to assess the anatomy of the coronary veins and MPS to identify areas of scar tissue in the LV myocardium—is instrumental in planning interventional procedures aimed at improving the effectiveness of CRT. The use of this strategy was associated with a higher proportion of patients who responded to CRT, as well as a more pronounced reduction in LV ESV after the procedure.

Discussion of Primary Results

One factor contributing to the lack of response to CRT is non-optimal positioning of the LV lead. Previous studies have shown that placing this lead within a scarred region does not result in meaningful hemodynamic improvement after CRT. In contrast, implanting the LV lead into a cardiac vein corresponding to viable myocardium and the region of late mechanical activation may improve both the frequency and effectiveness of CRT device implantation [17]. Understanding the anatomy of the coronary venous system prior to device implantation allows the interventional strategy to be optimized and enables assessment of access to the optimal pacing site. In addition, this approach makes it possible to reduce procedure duration, the radiation dose to the patient, and the volume of contrast agent used.

The effectiveness of CRT depends on the presence of sufficient viable myocardium capable of contracting in response to stimulation. Cardiac magnetic resonance imaging is considered the gold standard for quantitative assessment of myocardial scarring and is recommended for patients with CHF [18]. However, its widespread use is limited by the complexity and duration of the cardiac protocol, high cost, and the requirement for contrast administration. MPS may be an alternative method for assessing the extent of scarring in the LV myocardium; it is relatively accessible and easy to perform. It also demonstrates high intra- and interoperator reproducibility [19] and does not require additional contrast injection. In our study, we demonstrated the high utility of MPS and CT venography for optimal selection of the target vein when implanting the LV lead for CRT.

The findings of this study are consistent with previously published data. For example, Tada et al. [20] proposed an approach to optimizing the effectiveness of CRT device implantation based on analysis of preoperative MPS results and contrast-enhanced CT venography of the heart. Using these data, the authors evaluated coronary venous anatomy and LV myocardial perfusion to determine the optimal implantation site and to select a LV lead that corresponded to the anatomical characteristics of the target vein. All patients demonstrated a positive response to CRT. However, this method has not been tested in a large patient cohort (4 patients were included). The results of our study showed that using cardiovascular imaging to assess coronary sinus anatomy and myocardial perfusion preoperatively increases the proportion of patients with a positive CRT response. With this approach, the proportion of responders¹ reaches 82%, whereas in the comparison group it is 57% (p = 0.031).

According to the published data, a multimodal imaging approach prior to CRT device implantation may help reduce adverse effects on the patient by shortening the duration of the procedure, decreasing radiation exposure, and reducing the volume of contrast agent used. However, in our study, no statistically significant differences were identified between the two groups in fluoroscopy time or in the effective radiation dose received during the procedure. Nevertheless, performing CT venography and MPS before CRT provides additional information for selecting a left ventricular lead with optimal length and curvature that correspond to the anatomy of the target vein.

Study Limitations

A limitation of this study is the small sample size.

Furthermore, the sample size required to achieve adequate statistical power was not calculated during the study design or conduct. Therefore, the obtained sample cannot be considered sufficiently representative, which does not allow the results and their interpretation to be extrapolated to a broader population of similar patients outside the study.

CONCLUSION

The use of cardiovascular imaging methods, including CT venography of the heart and MPS, enables identification of the optimal site for LV lead implantation during CRT planning. This approach is associated with an increased proportion of patients responding positively to therapy. Nevertheless, further multicenter studies are required to determine its clinical effectiveness.

ADDITIONAL INFORMATION

Author contributions: A.I. Mishkina: investigation, data curation, writing—original draft, writing—review & editing; T.A. Atabekov: investigation, data curation, writing—original draft, writing—review & editing; S.I. Sazonova, R.E. Batalov, S.V. Popov: data curation, writing—original draft, writing—review & editing; K.V. Zavadovsky: conceptualization, data curation, writing—original draft, writing—review & editing. All the authors approved the version of the manuscript to be published and agreed to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Ethics approval: The study was approved by the Committee on Biomedical Ethics of the Cardiology Research Institute, Tomsk National Research Medical Center (protocol No. 232 dated October 26, 2022). All the participants provided written informed consent prior to inclusion in the study.

Funding sources: No funding.

Disclosure of interests: The authors have no relationships, activities, or interests for the last three years related to for-profit or not-for-profit third parties whose interests may be affected by the content of the article.

Statement of originality: No previously published material (text, images, or data) was used in this work.

Data availability statement: The editorial policy regarding data sharing does not apply to this work.

Generative AI: No generative artificial intelligence technologies were used to prepare this article.

Provenance and peer-review: This paper was submitted unsolicited and reviewed following the standard procedure. The peer review process involved an external reviewer and a member of the editorial board.

¹ A responder is a patient who responds positively to treatment, demonstrating the expected positive treatment outcome.