Multiple arterial grafting and the age threshold dilemma: a narrative review

Introduction

Background

Coronary artery bypass grafting (CABG) remains the gold standard for surgical revascularization in patients with multivessel coronary artery disease, with long-term outcomes being strongly influenced by conduit choice (1). Arterial grafts, particularly the internal thoracic artery (ITA), have consistently demonstrated superior long-term patency and survival benefits over saphenous vein grafts (SVGs) (2,3). Building on this foundation, multiple arterial grafting (MAG)—commonly involving bilateral internal thoracic arteries (BITAs), and occasionally supplemented by the radial artery—has emerged as a revascularization strategy that may further enhance survival, reduce cardiac events, and minimize the need for future interventions (4-6).

Rationale and knowledge gap

The rationale for MAG lies in the durable patency of arterial conduits, which are more resistant to atherosclerosis and occlusion compared to venous grafts (7). Observational studies have suggested that MAG confers a survival advantage beyond that achieved with single internal thoracic artery (SITA) and SVG combinations (8). However, the adoption of MAG in routine surgical practice remains low, especially among elderly patients (9). This underutilization is driven by concerns regarding operative complexity, risk of sternal wound complications, and uncertainty about the magnitude and durability of MAG’s benefit in older age cohorts (10,11).

Several studies have attempted to define a chronological age threshold beyond which the incremental benefit of MAG—particularly BITA—might diminish or be lost altogether (12-14). Some have identified age cut-offs at 60 or 69 years, suggesting an attenuation of survival advantage due to competing non-cardiac mortality or diminishing life expectancy (15). Others, however, argue that such rigid thresholds may be oversimplified and overlook physiological age, comorbid status, and contemporary refinements in surgical technique that could extend the benefits of MAG into older populations (16,17).

Despite numerous individual studies examining age as a determinant of MAG benefit, no prior review has systematically synthesized these findings or explored the methodological sources of variability, leaving a knowledge gap that this review aims to address.

Objective

This narrative review synthesizes current evidence regarding the age-related efficacy of MAG, with particular emphasis on BITA-based strategies. It critically examines data from key observational cohorts, explores methodological frameworks that have shaped interpretations of age-related outcomes, and highlights the evolving discourse that challenges rigid age-based cut-offs. The goal is to contextualize MAG decision-making within a framework of individualized care that balances survival benefit, surgical risk, and patient-centered outcomes. This article is presented in accordance with the Narrative Review reporting checklist (available at https://amj.amegroups.com/article/view/10.21037/amj-2025-1-75/rc).

Methods

A literature search was performed using PubMed and Embase databases from January 1990 to August 2025. The search was limited to studies published from January 1990 onward to ensure relevance to contemporary surgical practice and guideline-based conduit strategies. Search terms included “multiple arterial grafting”, “bilateral internal thoracic artery”, “coronary artery bypass”, “age threshold”, “frailty”, and “surgical outcomes” (Tables 1,2). Both MeSH terms and free-text keywords were used.

Inclusion criteria:

• Studies evaluating MAG or BITA outcomes stratified by age;
• Observational cohorts, registry analyses, and randomized trials;
• English-language publications.

Exclusion criteria:

• Case reports, editorials, and non-peer-reviewed sources;
• Studies lacking age-specific analysis.

Titles and abstracts were screened for relevance, followed by full-text review. Data were extracted on population size, age thresholds, methodology, and outcomes. Methodological quality and statistical modeling approaches were also assessed.

Historical context and evolution of arterial grafting

The evolution of CABG has been shaped by a growing understanding of conduit durability and its influence on long-term outcomes. The ITA first gained prominence following the landmark Cleveland Clinic study, which demonstrated that left ITA grafting to the left anterior descending artery significantly improved 10-year survival and reduced cardiac events compared to venous grafts alone (1). This pivotal evidence established SITA grafting as a standard of care, particularly in the context of left-sided coronary targets (1).

Subsequent efforts focused on expanding the use of arterial conduits beyond the left ITA. BITA grafting emerged as a promising technique, aiming to replicate the superior patency and resistance to atherosclerosis across multiple vascular territories (18). Observational studies suggested a further improvement in long-term survival and freedom from reintervention with BITA compared to SITA (19,20). This approach, in combination with the radial artery as a third conduit, laid the foundation for MAG strategies.

Despite accumulating evidence, the adoption of MAG—particularly BITA—has remained limited worldwide. Utilization rates in North America and Europe are consistently low, with BITA used in fewer than 10% of CABG procedures, especially in elderly and higher-risk populations (21,22). Surgeons have expressed concerns about increased operative complexity, risk of deep sternal wound infections, longer operative times, and a perceived lack of benefit in older patients with limited life expectancy (22).

In parallel, technical innovations such as skeletonized harvesting of the ITA, composite Y-grafts, and aortic no-touch techniques have aimed to reduce complication rates and expand arterial grafting to broader patient subsets (23,24). These refinements have gradually reshaped the early risk profile once associated with MAG, particularly among diabetic, obese, or elderly patients.

Nevertheless, the prevailing practice remains conservative in many institutions, with arterial grafting strategies tailored based on a combination of age, comorbid burden, and surgeon preference. The historical shift from age-independent enthusiasm to risk-based caution reflects the ongoing tension between perceived versus proven benefit in specific cohorts (6). This evolution has spurred a critical need to clarify the age threshold—if any—beyond which the incremental benefit of MAG is significantly diminished, forming the central focus of the current review.

Evidence for age-dependent benefit

Determining whether the survival advantage associated with MAG—particularly BITA use—persists across all age groups has been the subject of extensive investigation (8,12,25-28). Early studies raised concerns that the benefit may diminish in elderly patients due to reduced life expectancy, competing non-cardiac mortality, and increased perioperative risk (13,15,17,25). The following is a chronological synthesis of the most influential studies evaluating age as a determinant of BITA efficacy (15,25-29) (Figure 1, Table 3).

Figure 1 Study selection diagram. CABG, coronary artery bypass grafting; MAG, multiple arterial grafting.

To contextualize these findings, it is important to recognize the methodological heterogeneity across the key studies summarized in Table 3, particularly with respect to matching and statistical adjustment. Among the six core manuscripts, two employed formal propensity score matching to balance baseline characteristics between treatment groups: Pettinari et al. matched 1,784 elderly patients (≥70 years) (27), while Toumpoulis et al. conducted agestratified analyses within a propensitymatched diabetic cohort (29). Benedetto et al. used flexible parametric spline modeling with ageinteraction terms to evaluate treatment effect continuously across the age spectrum, minimizing misclassification bias inherent to categorical age thresholds (26). Kieser et al. (25) and Mohammadi et al. (15) relied on multivariable Cox proportional hazards models with adjustment for key clinical covariates, and although unmatched, these studies provided age‑specific hazard estimates derived from large, well‑characterized cohorts. Finally, Ren et al. (28) analyzed 69,624 patients using multivariate and hierarchical modeling; despite the absence of matching, the scale and statistical rigor of this registry allowed robust evaluation of age-treatment interactions. These methodological considerations are essential for interpreting the apparent variability in reported age thresholds and for understanding how analytic approach influences observed treatment effects. Interpretation of late outcomes is further complicated by inconsistent reporting of conduit configurations, particularly the use of supplementary SVGs in MAG cohorts. Because vein graft failure is a major driver of late cardiac events, variability in mixed arterial-venous strategies may partly explain the heterogeneity observed across studies.

In 2006, Toumpoulis et al. explored whether age modified outcomes in diabetic patients undergoing CABG. Their age-stratified analysis revealed that BITA conferred a survival benefit only among patients aged 60–69 years. No statistically significant advantage was observed for patients younger than 60 years or older than 70 years, implying a potential “therapeutic window” for arterial revascularization in this population (29).

Mohammadi et al., in a large retrospective analysis of over 12,000 patients, identified age 60 years as a threshold beyond which the benefit of BITA on cardiac-specific survival diminished and ultimately became clinically and statistically non-significant (15). Nonetheless, the use of at least one ITA remained superior to vein-only grafting in all age groups, including octogenarians.

Kieser et al. subsequently examined 1,038 patients to evaluate whether BITA use improved long-term survival in those over age 65 years. While age was acknowledged as a potential effect modifier, the study failed to demonstrate a consistent benefit from BITA after adjustment for clinical variables. As a result, no definitive age cut-off was identified (25).

Building on this, a significant contribution came in 2014 from Benedetto et al., who employed flexible parametric spline modeling in a cohort of 4,190 patients to more precisely quantify age-related treatment effects. Their analysis revealed that BITA use was associated with a 51% reduction in mortality for patients aged ≤69 years [hazard ratio (HR) 0.49; P=0.04], whereas no meaningful benefit was observed in those older than 69 years (HR 1.27; P=0.37) (26). This was the first study to define an age threshold using data-driven modeling rather than arbitrary age brackets.

In contrast, Pettinari et al. analyzed outcomes in 1,784 propensity-matched patients aged ≥70 years and reported a significant survival advantage with BITA grafting at 10 years (57.5% vs. 38.9%; P=0.02) compared to SITA, with no increase in stroke, myocardial infarction, or sternal wound complications (27). Their findings challenge the widespread underutilization of MAG in elderly cohorts and suggest that, with appropriate selection, BITA can confer meaningful longevity benefits without added perioperative morbidity.

Challenging the consensus of diminishing returns, Ren et al. published a large national registry analysis in 2024 demonstrating that MAG was associated with a significant survival advantage even in patients aged ≥70 years [HR 0.84; 95% confidence interval (CI): 0.79–0.88; P<0.001] (28). The persistent and progressive divergence in survival curves between MAG and SITA across all age categories underscored the potential for carefully selected elderly patients to benefit from more aggressive arterial revascularization.

Collectively, these studies trace a trajectory from early caution to more nuanced, data-driven insights. While most evidence supports a declining incremental benefit of BITA with advancing age—especially beyond 60 to 70 years—emerging data advocate for avoiding rigid cut-offs. The variability in findings reflects differences in patient populations, analytic methodology, and surgical technique. Taken together, these observations underscore the importance of personalized revascularization strategies that incorporate chronological age alongside comorbid burden, life expectancy, and technical feasibility.

Statistical modeling and methodological considerations

The interpretation of age-related efficacy in MAG hinges not only on clinical outcomes but also on the statistical tools and methodological frameworks underpinning the evidence base (6,8,12,26). As studies have moved from descriptive analyses to more sophisticated modeling approaches, insights into the interaction between age and BITA benefit have evolved accordingly (8,12,25,28).

Early observational studies primarily relied on stratified subgroup analysis or multivariable Cox proportional hazards regression to evaluate the influence of age on survival outcomes (15,25,29). While these methods controlled for baseline imbalances and allowed for adjustments across key covariates, they often categorized age into arbitrarily defined groups, such as ≤60 or ≥70 years. This approach, though practical, risks oversimplifying the non-linear and potentially continuous relationship between age and treatment effect.

A more nuanced methodology was adopted by Benedetto et al., who utilized flexible parametric spline survival modeling to examine how the survival benefit from BITA varied across the age spectrum (26). This technique allowed the identification of a discrete inflection point—age 69 years—beyond which BITA conferred no statistically significant survival advantage. By treating age as a continuous variable and modeling interaction terms (age × BITA), the analysis minimized misclassification bias and improved interpretability, providing a data-derived threshold rather than one selected a priori.

Despite these advances, important methodological limitations persist. Most studies to date are observational and retrospective in design, lacking the rigor and internal validity of randomized controlled trials (RCTs) (5,8,12,25,28). Confounding by indication is a particular concern: younger, lower-risk patients are more likely to receive MAG, while older or comorbid patients are often directed toward more conservative grafting strategies. While propensity score matching and multivariable adjustment techniques mitigate this issue to some extent, residual confounding cannot be excluded (27,28).

Another limitation is the variability in surgical techniques and conduit configuration. Differences in skeletonization versus pedicled harvest of the ITA, use of composite versus in-situ grafting, and addition of radial arteries are seldom standardized across studies. These technical factors may modify both short- and long-term outcomes, yet they are frequently underreported or inconsistently defined.

Additionally, most survival analyses focus on all-cause or cardiac-specific mortality, but do not account for other clinically relevant endpoints such as major adverse cardiac events (MACE), anginal burden, quality of life, or need for reintervention. In elderly patients, especially, functional outcomes and postoperative recovery may be more meaningful than incremental gains in long-term survival (30).

Finally, small event numbers in certain subgroups—particularly octogenarians receiving BITA—can limit statistical power and inflate uncertainty in effect estimates. While large registries such as those used by Ren et al. help overcome this limitation through scale, they often lack granular data on operative technique, conduit configuration, or surgeon experience, which are critical to proper interpretation (28).

Taken together, while the evolution in statistical methodology has enhanced the precision of age-threshold detection, caution is warranted when extrapolating findings across diverse patient populations and institutional contexts. Future studies, ideally leveraging prospective designs and core procedural standardization, will be essential to definitively delineate the role of age in determining MAG benefit.

Beyond chronological age: risk stratification and frailty

While age has served as a convenient surrogate for surgical risk in CABG, it is increasingly recognized as a crude and insufficient measure for guiding conduit strategy. Chronological age alone fails to capture the biological heterogeneity observed among older patients, particularly those with varying levels of frailty, comorbid burden, and functional reserve (31). As MAG evolves, so too must the methods for selecting appropriate candidates—shifting from age-based thresholds to more holistic, individualized assessments.

Frailty, a multidimensional syndrome characterized by diminished physiologic reserve and vulnerability to stressors, is emerging as a key determinant of postoperative outcomes in cardiac surgery (31-33). Frailty has been shown to predict not only early morbidity and mortality but also longer-term functional decline, prolonged recovery, and diminished quality of life. Several scoring systems—including the Fried phenotype, the Clinical Frailty Scale, and gait speed tests—have been validated as predictors of poor surgical tolerance, even among patients with acceptable chronological age (32,33).

Comorbidities such as diabetes, chronic obstructive pulmonary disease, obesity, and renal dysfunction further complicate the decision-making process. For instance, while diabetic patients may theoretically derive greater long-term benefit from total arterial revascularization, they also face increased risk of sternal wound complications with BITA harvest—particularly in the setting of obesity or poor glycemic control (34,35). Similarly, female sex, which is often underrepresented in randomized trials, has been associated with increased operative risk in some MAG studies, though this may be confounded by smaller body habitus and more diffuse coronary disease (36).

The concept of physiologic age—anchored in frailty indices, comorbidity burden, and cardiopulmonary reserve—offers a more nuanced framework for conduit selection. Contemporary guidelines from the American Heart Association and European Association for Cardio-Thoracic Surgery advocate for individualized risk-benefit assessments that extend beyond simple age cut-offs (37,38). High-resolution imaging (e.g., CT chest for sternal quality or aortic calcification), risk scoring tools (e.g., EuroSCORE II, STS Risk Calculator), and multidisciplinary input via Heart Teams can further refine patient selection and facilitate shared decision-making.

Emerging approaches such as machine learning models, which integrate multimodal data—including frailty scores, imaging, biomarkers, and intraoperative factors—may eventually provide real-time prognostic tools to guide conduit strategy. Until such tools are universally available and validated, clinical judgment, surgeon experience, and patient preference remain central to aligning the invasiveness of surgical intervention with expected benefit.

Ultimately, the use of MAG should not be reflexively withheld from older patients solely due to age. Rather, conduit choice should reflect a composite of biological age, technical feasibility, perioperative risk, and the patient’s values and goals. As surgical teams move toward precision revascularization, incorporating frailty and individualized metrics will be essential to optimizing outcomes across the age spectrum.

Emerging contradictions and evolving perspectives

While early and mid-2000s observational studies (13,15,17,25) consistently suggested that the survival advantage of BITA grafting was attenuated in older patients—typically beyond 60 to 70 years—recent data challenge this narrative and prompt a re-examination of previously accepted thresholds (8,12,27,28). These emerging perspectives reflect the dynamic interplay between evolving surgical techniques, broader patient selection, and improvements in perioperative care.

One of the most consequential contributions to this evolving discourse is the national registry analysis by Ren et al., which demonstrated a clear and sustained survival benefit of MAG even in patients aged 70 years and older (28). Among this cohort, those undergoing MAG experienced a 16% relative reduction in all-cause mortality (HR 0.84; 95% CI: 0.79–0.88; P<0.001) compared to those receiving SITA–based revascularization. Notably, the survival curves for both younger and older patients exhibited progressive divergence in favor of MAG—a pattern indicative of durable benefit, not merely short-term selection bias.

These findings challenge the foundational conclusions drawn from earlier studies that employed smaller cohorts, more variable surgical techniques, and statistical models that often stratified age into coarse categories or failed to fully capture interaction effects (13,15,17,19,20). The increasing use of skeletonized BITA harvesting, improved infection control protocols, and composite conduit configurations likely mitigate the historical concerns regarding sternal wound complications, particularly in older or high-risk patients (39,40).

Another important consideration lies in institutional and operator experience. Centers that routinely perform MAG, including BITA or radial-based Y-composite grafting, report lower morbidity and superior long-term outcomes across all age groups, suggesting that surgical expertise may moderate age-related risk (41). This variability may in part explain the conflicting findings across cohorts and further supports the notion that age should not be treated as an absolute contraindication to MAG, but rather as a contextual factor influenced by team experience and technique.

Contemporary guidelines have begun to reflect this shift in perspective. The 2018 ESC/EACTS Myocardial Revascularization Guidelines and the 2016 STS Arterial Conduit Guidelines advocate for increased consideration of MAG in appropriate patients, without imposing strict upper age limits, instead recommending individualized assessment of risk, anatomy, and life expectancy (9,38).

Nonetheless, residual equipoise remains. While registry data offer broad generalizability, they are inherently limited by confounding and lack the granularity required to assess technical nuances. The absence of RCTs specifically powered to detect age-treatment interaction leaves room for uncertainty. Importantly, much of the literature to date focuses on survival rather than quality of life, cognitive outcomes, or patient-reported benefit—domains of particular relevance to elderly patients.

In sum, the emerging body of evidence encourages a paradigm shift from rigid age-based exclusion toward a more nuanced, evidence-aligned, and technique-sensitive application of MAG. As datasets become more granular and surgical innovation continues to narrow the risk gap, age may increasingly be seen as a factor to be navigated—not a barrier to be obeyed.

Technical modifiers and solutions

The risk-benefit profile of MAG, especially with BITA harvest, has historically raised concerns in elderly patients due to perceived technical complexity and increased susceptibility to sternal wound complications (13). However, several technical adaptations have emerged that significantly reduce perioperative risk, enabling safe application of MAG strategies in broader patient populations—including those traditionally considered marginal candidates.

Skeletonized ITA harvesting

Skeletonization involves harvesting the ITA with minimal surrounding tissue, preserving collateral blood flow to the sternum. This technique has been shown in meta-analyses to significantly reduce the incidence of deep sternal wound infections compared to pedicled grafts, particularly in diabetic and obese patients (42,43). Additionally, skeletonization yields longer conduit length and increased graft versatility, facilitating composite configurations and reducing conduit tension.

Composite and Y-grafting configurations

The use of composite Y-grafts—most commonly left ITA to left anterior descending artery with right ITA or radial artery in Y or T fashion—eliminates the need for aortic anastomosis, reducing the risk of cerebrovascular events associated with aortic manipulation. These configurations also enable total arterial revascularization in patients with calcified ascending aortas or extensive vascular disease (44). Importantly, composite grafts reduce operative time and blood loss, particularly in reoperative or frail patients.

Integration of the radial artery

The radial artery, with its proven long-term patency and resistance to atherosclerosis, serves as a versatile adjunct in MAG—either as a free graft or as part of composite configurations. In patients where BITA harvesting is contraindicated (e.g., poor sternal integrity, prior thoracic radiation), the radial artery offers a robust alternative that maintains the benefits of arterial revascularization. Endoscopic harvesting techniques have further reduced donor site morbidity and improved procedural appeal (45,46).

Minimally invasive and hybrid approaches

Emerging minimally invasive CABG techniques, including robotic-assisted and thoracoscopic conduit harvesting, allow for reduced surgical trauma, expedited recovery, and preservation of thoracic integrity. These modalities, though not yet widespread, hold promise for expanding MAG in the elderly by limiting the physiological burden of traditional median sternotomy (47). In selected cases, hybrid revascularization combining minimally invasive arterial grafting with percutaneous coronary intervention may also offer a tailored approach that balances invasiveness with durability.

Standardization and surgeon experience

Institutional and operator experience remains a critical determinant of MAG outcomes. Centers with established expertise in arterial revascularization consistently demonstrate lower complication rates and greater survival benefit across age groups (6). Protocol-driven approaches to skeletonization, infection prophylaxis, conduit selection, and intraoperative flow assessment enhance consistency, mitigate variability, and make technically demanding procedures reproducible and safe.

In summary, the perception of MAG as inherently high risk in older adults is increasingly outdated. With contemporary techniques—ranging from skeletonization and Y-grafting to minimally invasive harvesting and hybrid approaches—surgeons are now equipped to deliver the benefits of total arterial revascularization to a wider and more complex patient population.

Clinical implications and shared decision-making

The decision to pursue MAG, particularly strategies involving BITA, must ultimately be framed not only by statistical outcomes and surgical feasibility but by the lived realities, values, and priorities of individual patients. The translation of evidence into practice hinges on clinical equipoise, transparent communication, and shared decision-making—especially in older adults, where the margin of benefit may narrow and competing risks often accrue.

For younger, low-risk patients, the rationale for MAG is generally straightforward: robust observational data and emerging registry evidence demonstrate survival benefit (8,12,25,26,28,41), reduced graft failure (3,18), and lower risk of repeat revascularization (8,41,48). In such cases, the key clinical task lies in encouraging appropriate utilization and overcoming inertia or institutional variability in grafting practices.

In contrast, for older patients—especially those over 70 years—the calculus is more nuanced. Although studies such as Ren et al. (28) affirm that MAG can be beneficial in selected elderly cohorts, the incremental survival gain must be weighed against potential increases in operative complexity, resource utilization, and convalescence duration. Here, functional status, frailty, cognitive reserve, and patient-reported outcome priorities (e.g., return to independence, avoidance of prolonged recovery) should guide discussion.

Shared decision-making becomes particularly critical in this context. Patients and their families should be engaged in transparent, evidence-informed discussions that encompass the expected long-term benefits of the procedure—such as improved survival and symptom relief—as well as the potential procedural risks, including sternal wound complications and the possibility of prolonged postoperative support. These conversations should also explore alternative revascularization options, such as single ITA grafting in combination with SVGs, and should center the patient’s personal values and preferences, whether they prioritize long-term durability or favor a less invasive intervention with quicker recovery (49).

The Heart Team model—uniting cardiac surgeons, interventional cardiologists, anesthetists, geriatricians, and patient advocates—facilitates a multidimensional view of the treatment landscape. This approach is particularly valuable in anatomically complex cases or elderly patients with borderline surgical candidacy, and is endorsed by contemporary revascularization guidelines (37,38).

Moreover, emerging tools such as decision aids, frailty scoring instruments, and individualized risk calculators (e.g., STS Risk Score, EuroSCORE II) provide tangible ways to personalize the grafting strategy and quantify trade-offs. Future iterations may incorporate AI-powered predictive analytics that stratify benefit in real time across various conduit configurations (6).

Finally, institutional culture matters. Centers that proactively offer MAG to a spectrum of patients—not just the idealized young, male, low-risk cohort—signal a commitment to tailored, durable care. Auditing local MAG rates by age group, gender, and comorbidity profile can serve as a valuable quality improvement metric.

The decision to employ MAG should not default to age nor be dictated solely by statistical models. It must arise from an informed, collaborative process that honors both the science and the patient’s preferences—a convergence of precision surgery and empathetic medicine.

Gaps in evidence and future directions

Despite the increasing sophistication of statistical models and the accumulating volume of observational data, several critical gaps persist in the evidence supporting MAG, particularly as it relates to age-stratified outcomes. The reliance on retrospective cohort studies—though informative—limits causal inference and introduces challenges such as unmeasured confounding, selection bias, and inconsistent reporting of surgical techniques. RCTs, which could definitively address these limitations, remain scarce.

The Arterial Revascularization Trial (ART), while pivotal, was not adequately powered to evaluate age–treatment interactions and was compromised by substantial crossover between treatment arms, diluting its ability to detect differences between bilateral and single ITA grafting (5). Ongoing or future trials with stratification by chronological and physiological age will be essential to determine whether the survival benefit of MAG meaningfully extends into older cohorts, and under what technical or perioperative conditions.

Moreover, most studies to date have disproportionately emphasized all-cause or cardiac-specific mortality as the primary endpoint (8,12,25,26,28). While these are objective and readily obtainable, they fail to capture outcomes of growing importance to older patients: functional status, angina burden, quality of life (QoL), cognitive trajectory, and independence. These parameters—rarely included in major datasets—are fundamental to understanding the true value of arterial revascularization in an aging population.

Another underexplored domain is the role of artificial intelligence (AI), machine learning, and advanced imaging in conduit selection and risk prediction. Integrating high-dimensional data—such as frailty indices, coronary anatomy, myocardial viability, and procedural complexity—may enable granular, individualized modeling of MAG benefit. This could support dynamic, intraoperative decision-making rather than reliance on static age thresholds.

Additionally, there is a need for standardized reporting and longitudinal tracking of technical details, including conduit configuration, skeletonization, and flow measurements. Current registry data often lack such granularity, hindering meaningful comparison across institutions or patient strata (8,21,22,28). The development of international arterial grafting consortia with unified reporting frameworks may facilitate more robust, reproducible insights.

Finally, the uptake of MAG remains suboptimal in many centers, even among ideal candidates. Implementation research, including studies focused on barriers to adoption, surgical training pathways, and institutional volume–outcome relationships, is vital to translate evolving evidence into routine practice. Educational interventions, procedural mentorship, and institutional benchmarking may help close the gap between best evidence and real-world practice.

In summary, as the demographic of surgical candidates continues to shift toward older and more complex patients, the pursuit of refined, patient-centered, and evidence-aligned strategies for MAG becomes increasingly urgent. Addressing the current evidence gaps—through pragmatic trials, functional endpoints, and precision tools—will shape the future trajectory of coronary revascularization (Table 4).

This review should be interpreted in light of several limitations inherent to the included literature. Although the combined sample encompasses approximately 90,000 patients, a single large registry study (28) contributes nearly 70,000 cases, introducing disproportionate weighting and potential selection bias. Across studies, heterogeneity in conduit configurations, inconsistent reporting of supplementary vein graft use, and variability in age‑stratified analyses further complicate interpretation. Most available data are observational, limiting causal inference despite advanced statistical adjustment. Nonetheless, the review’s strengths include its integration of contemporary and historical evidence, its focus on methodological drivers of heterogeneity, and its clarification of the evolving relationship between age and MAG benefit.

Conclusions

The evolution of MAG has marked a paradigm shift in CABG, aiming to enhance long-term outcomes through the superior durability of arterial conduits. Yet, for decades, the application of MAG—especially BITA strategies—has been modulated by concerns regarding age-related risk and diminishing returns in elderly patients.

This review highlights that while early observational studies suggested a decline in BITA benefit beyond 60–70 years, more recent, methodologically rigorous analyses challenge the validity of these thresholds. Emerging data from large registries indicate that MAG may confer survival advantages well into older age, particularly when guided by meticulous technique, frailty assessment, and individualized risk stratification. As surgical expertise, conduit configurations, and perioperative management continue to evolve, the technical limitations that once justified a conservative approach are no longer as definitive.

Importantly, age alone—divorced from physiological reserve, comorbidity profile, and patient preference—is an insufficient metric for conduit selection. Transitioning from algorithmic to nuanced, patient-centered strategies requires not only robust evidence but also cultural shifts in clinical practice, surgical training, and shared decision-making frameworks.

Looking ahead, the refinement of predictive tools, the inclusion of functional and quality-of-life endpoints, and prospective trials addressing age–treatment interactions will be critical to solidifying the role of MAG across the age spectrum. In the interim, thoughtful application of existing evidence—aligned with technical excellence and individual values—offers the most promising route to optimizing revascularization outcomes for all patients, regardless of chronological age.

Acknowledgments

None.

Footnote

Reporting Checklist: The author has completed the Narrative Review reporting checklist. Available at https://amj.amegroups.com/article/view/10.21037/amj-2025-1-75/rc

Peer Review File: Available at https://amj.amegroups.com/article/view/10.21037/amj-2025-1-75/prf

Funding: None.

Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at https://amj.amegroups.com/article/view/10.21037/amj-2025-1-75/coif). S.G.R. serves as an unpaid Associate Editor-in-Chief of AME Medical Journal from January 2025 to December 2026. The author has no other conflicts of interest to declare.

Ethical Statement: The author is accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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References

1. Loop FD, Lytle BW, Cosgrove DM, et al. Influence of the internal-mammary-artery graft on 10-year survival and other cardiac events. N Engl J Med 1986;314:1-6. [Crossref] [PubMed]
2. Cameron A, Davis KB, Green G, et al. Coronary bypass surgery with internal-thoracic-artery grafts--effects on survival over a 15-year period. N Engl J Med 1996;334:216-9. [Crossref] [PubMed]
3. Goldman S, Zadina K, Moritz T, et al. Long-term patency of saphenous vein and left internal mammary artery grafts after coronary artery bypass surgery: results from a Department of Veterans Affairs Cooperative Study. J Am Coll Cardiol 2004;44:2149-56. [Crossref] [PubMed]
4. Gaudino M, Benedetto U, Fremes S, et al. Radial-Artery or Saphenous-Vein Grafts in Coronary-Artery Bypass Surgery. N Engl J Med 2018;378:2069-77. [Crossref] [PubMed]
5. Taggart DP, Altman DG, Gray AM, et al. Randomized Trial of Bilateral versus Single Internal-Thoracic-Artery Grafts. N Engl J Med 2016;375:2540-9. [Crossref] [PubMed]
6. Raja SG. Multiple Arterial Grafting in CABG: Outcomes, Concerns, and Controversies. J Vasc Dis 2025;4:29.
7. Gharibeh L, Ferrari G, Ouimet M, et al. Conduits' Biology Regulates the Outcomes of Coronary Artery Bypass Grafting. JACC Basic Transl Sci 2021;6:388-96. [Crossref] [PubMed]
8. Rocha RV, Tam DY, Karkhanis R, et al. Multiple Arterial Grafting Is Associated With Better Outcomes for Coronary Artery Bypass Grafting Patients. Circulation 2018;138:2081-90. [Crossref] [PubMed]
9. Aldea GS, Bakaeen FG, Pal J, et al. The Society of Thoracic Surgeons Clinical Practice Guidelines on Arterial Conduits for Coronary Artery Bypass Grafting. Ann Thorac Surg 2016;101:801-9. [Crossref] [PubMed]
10. Al-Tawil M, Alqeeq BF, Jaffar-Karballai M, et al. The Best Second Arterial Conduit for Coronary Artery Bypass Grafting: A Meta-Analysis of Reconstructed Individual Patient Data. Cardiol Rev 2024; Epub ahead of print. [Crossref]
11. Waterford SD. Barriers to Multiarterial Coronary Artery Bypass Grafting. Innovations (Phila) 2024;19:345-50. [Crossref] [PubMed]
12. Mulder BS, Candura D, Schoones JW, et al. Meta-Analysis of Bilateral Versus Single Internal Thoracic Artery Grafting in Patients ≥70 Years of Age. Am J Cardiol 2022;173:48-55. [Crossref] [PubMed]
13. Hirotani T, Nakamichi T, Munakata M, et al. Extended use of bilateral internal thoracic arteries for coronary artery bypass grafting in the elderly. Jpn J Thorac Cardiovasc Surg 2003;51:488-95. [Crossref] [PubMed]
14. Itoh S, Kimura N, Adachi H, et al. Is Bilateral Internal Mammary Arterial Grafting Beneficial for Patients Aged 75 Years or Older? Circ J 2016;80:1756-63. [Crossref] [PubMed]
15. Mohammadi S, Dagenais F, Doyle D, et al. Age cut-off for the loss of benefit from bilateral internal thoracic artery grafting. Eur J Cardiothorac Surg 2008;33:977-82. [Crossref] [PubMed]
16. Kurlansky PA, Traad EA, Dorman MJ, et al. Bilateral Versus Single Internal Mammary Artery Grafting in the Elderly: Long-Term Survival Benefit. Ann Thorac Surg 2015;100:1374-81; discussion 1381-2. [Crossref] [PubMed]
17. Gatti G, Dell'Angela L, Benussi B, et al. Bilateral internal thoracic artery grafting in octogenarians: where are the benefits? Heart Vessels 2016;31:702-12. [Crossref] [PubMed]
18. Gaudino M, Hameed I, Robinson NB, et al. Angiographic Patency of Coronary Artery Bypass Conduits: A Network Meta-Analysis of Randomized Trials. J Am Heart Assoc 2021;10:e019206. [Crossref] [PubMed]
19. Gansera B, Loef A, Angelis I, et al. Double thoracic artery--halved mid-term mortality? A 5-year follow-up of 716 patients receiving bilateral ITA versus 662 patients with single ITA. Z Kardiol 2004;93:878-83.
20. Deutsch O, Gansera L, Wunderlich M, et al. Does Bilateral ITA Grafting Increase Perioperative Complications? Outcome of 6,476 Patients with Bilateral versus 5,020 Patients with Single ITA Bypass. Thorac Cardiovasc Surg 2016;64:188-94.
21. Ramsingh R, Bakaeen FG. Coronary artery bypass grafting: Practice trends and projections. Cleve Clin J Med 2025;92:181-91. [Crossref] [PubMed]
22. Raja SG. Global trends and practices in coronary artery bypass surgery. Academia Medicine 2025;2: [Crossref]
23. Dalén M, Dismorr M, Glaser N, et al. Skeletonized Versus Pedicled Harvesting of the Internal Thoracic Artery and Long-Term Clinical Outcomes in Coronary Artery Bypass Surgery. J Am Heart Assoc 2024;13:e034354. [Crossref] [PubMed]
24. Oliveira Sá MP, Santos CA, Figueiredo OJ, et al. Skeletonized internal thoracic artery is associated with lower rates of mediastinitis in elderly undergoing coronary artery bypass grafting surgery. Rev Bras Cir Cardiovasc 2011;26:617-23. [Crossref] [PubMed]
25. Kieser TM, Lewin AM, Graham MM, et al. Outcomes associated with bilateral internal thoracic artery grafting: the importance of age. Ann Thorac Surg 2011;92:1269-75; discussion 1275-6. [Crossref] [PubMed]
26. Benedetto U, Amrani M, Raja SG, et al. Guidance for the use of bilateral internal thoracic arteries according to survival benefit across age groups. J Thorac Cardiovasc Surg 2014;148:2706-11. [Crossref] [PubMed]
27. Pettinari M, Sergeant P, Meuris B. Bilateral internal thoracic artery grafting increases long-term survival in elderly patients. Eur J Cardiothorac Surg 2015;47:703-9. [Crossref] [PubMed]
28. Ren J, Royse C, Srivastav N, et al. Long-Term Survival of Multiple Versus Single Arterial Coronary Bypass Grafting in Elderly Patients. J Clin Med 2023;12:2594. [Crossref] [PubMed]
29. Toumpoulis IK, Anagnostopoulos CE, Balaram S, et al. Does bilateral internal thoracic artery grafting increase long-term survival of diabetic patients? Ann Thorac Surg 2006;81:599-606; discussion 606-7. [Crossref] [PubMed]
30. Järvinen O, Saarinen T, Julkunen J, et al. Changes in health-related quality of life and functional capacity following coronary artery bypass graft surgery. Eur J Cardiothorac Surg 2003;24:750-6. [Crossref] [PubMed]
31. James K, Jamil Y, Kumar M, et al. Frailty and Cardiovascular Health. J Am Heart Assoc 2024;13:e031736. [Crossref] [PubMed]
32. Lee JA, Yanagawa B, An KR, et al. Frailty and pre-frailty in cardiac surgery: a systematic review and meta-analysis of 66,448 patients. J Cardiothorac Surg 2021;16:184. [Crossref] [PubMed]
33. Chandiramani A, Ali JM. Frailty in Cardiac Surgery-Assessment Tools, Impact on Outcomes, and Optimisation Strategies: A Narrative Review. J Cardiovasc Dev Dis 2025;12:127. [Crossref] [PubMed]
34. Nolan J, Wijaya AR, Harta IKAP. Meta-analysis of BITA versus SITA grafting in diabetic patients: evidence from propensity score-matched studies. Gen Thorac Cardiovasc Surg 2025;73:80-7. [Crossref] [PubMed]
35. Stefil M, Dixon M, Benedetto U, et al. Coronary artery bypass grafting using bilateral internal thoracic arteries in patients with diabetes and obesity: A systematic review and meta-analysis. Int J Cardiol Heart Vasc 2023;47:101235. [Crossref] [PubMed]
36. Rubens FD, Wells GA, Coutinho T, et al. Sex differences after coronary artery bypass grafting with a second arterial conduit. J Thorac Cardiovasc Surg 2022;163:686-95.
37. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 2022;145:e4-e17. [Crossref] [PubMed]
38. Neumann FJ, Sousa-Uva M, Ahlsson A, et al. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J 2019;40:87-165. [Crossref] [PubMed]
39. Schwann TA, Gaudino MFL, Engelman DT, et al. Effect of Skeletonization of Bilateral Internal Thoracic Arteries on Deep Sternal Wound Infections. Ann Thorac Surg 2021;111:600-6. [Crossref] [PubMed]
40. Rubens FD, Chen L, Bourke M. Assessment of the Association of Bilateral Internal Thoracic Artery Skeletonization and Sternal Wound Infection After Coronary Artery Bypass Grafting. Ann Thorac Surg 2016;101:1677-82. [Crossref] [PubMed]
41. Ding Q, Zhu Q, Lu L, et al. Comparison of multiple arterial grafts vs. single arterial graft in coronary artery bypass surgery: a systematic review and meta-analysis. Front Cardiovasc Med 2025;12:1555242.
42. Dimagli A, Gemelli M, Kumar N, et al. A systematic review and meta-analysis of internal thoracic artery harvesting techniques: Skeletonized vs pedicled. Int J Cardiol 2024;395:131577. [Crossref] [PubMed]
43. Kusu-Orkar TE, Kermali M, Masharani K, et al. Skeletonized or Pedicled Harvesting of Left Internal Mammary Artery: A Systematic Review and Meta-analysis. Semin Thorac Cardiovasc Surg 2021;33:10-8. [Crossref] [PubMed]
44. Raja SG. Composite arterial grafting. Expert Rev Cardiovasc Ther 2006;4:523-33. [Crossref] [PubMed]
45. Rankin JS, Mehaffey JH, Chu D, et al. Techniques and Results of Multiple Arterial Bypass Grafting: Towards More "Curative" Coronary Revascularizations. Semin Thorac Cardiovasc Surg 2025;37:12-21. [Crossref] [PubMed]
46. Sandner S, Antoniades C, Caliskan E, et al. Intra-operative and post-operative management of conduits for coronary artery bypass grafting: a clinical consensus statement of the European Society of Cardiology Working Group on Cardiovascular Surgery and the European Association for Cardio-Thoracic Surgery Coronary Task Force. Eur J Cardiothorac Surg 2024;66:ezae400. [Crossref] [PubMed]
47. Nambiar P, Mittal C. Minimally invasive coronary bypass using internal thoracic arteries via a left minithoracotomy: "the Nambiar Technique". Innovations (Phila) 2013;8:420-6. [Crossref] [PubMed]
48. Audisio K, Soletti GJ, Robinson NB, et al. Multiple Arterial Grafting: For Every Patient and Every Surgeon? Innovations (Phila) 2021;16:214-5. [Crossref] [PubMed]
49. Hoque F. Shared Decision-Making in Patient Care: Advantages, Barriers and Potential Solutions. J Brown Hosp Med 2024;3:13-5. [Crossref] [PubMed]