Management of Coronary Artery Disease in Patients With Severe Aortic Stenosis

Author's summary

The coexistence of severe aortic stenosis and coronary artery disease presents diagnostic and therapeutic complexities, particularly in younger, lower-risk patients. This review highlights unmet needs in defining optimal revascularization timing, physiologic assessment cutoffs, and long-term coronary access strategies. It synthesizes emerging data from recent trials and explores evolving concepts such as commissural alignment and lifetime management planning. Addressing these gaps is essential to guide individualized, evidence-based care that balances immediate procedural success with future intervention feasibility and durability.

Abstract

The coexistence of severe aortic stenosis (AS) and coronary artery disease (CAD) presents complex diagnostic and therapeutic challenges, particularly as transcatheter aortic valve replacement (TAVR) expands to younger, lower-risk populations. CAD prevalence in AS patients ranges from 27.7% in low-risk cohorts to 74.9% in high-risk populations, synergistically worsening ventricular function and prognosis. Diagnostic evaluation remains challenging due to overlapping symptomatology and altered coronary physiology in severe AS. While invasive coronary angiography remains the gold standard, coronary computed tomography (CT) angiography with CT-derived fractional flow reserve (FFR) shows promise as a non-invasive alternative. Standard FFR thresholds may not be reliable in AS patients, with emerging evidence suggesting AS-specific cutoffs may be needed. Treatment strategies must balance the complexity of CAD with patient risk profiles. Current guidelines recommend bypass surgery with surgical aortic valve replacement for complex multivessel disease, while percutaneous coronary intervention (PCI) with TAVR is preferred for less complex lesions or high-risk patients. The optimal timing of PCI relative to TAVR remains debated, with recent data favoring a “TAVR-first” approach for non-critical lesions. As TAVR extends to younger patients, lifetime management considerations become paramount, including valve durability, future coronary access, and planning for potential re-interventions. Commissural alignment techniques during TAVR are crucial for preserving future coronary access. A multidisciplinary Heart Team approach with robust shared decision-making is essential for optimizing individualized care in this evolving field.

INTRODUCTION: EPIDEMIOLOGY AND CLINICAL SIGNIFICANCE OF CONCOMITANT CORONARY ARTERY DISEASE IN SEVERE AORTIC STENOSIS

Severe aortic stenosis (AS) and coronary artery disease (CAD) are highly prevalent cardiovascular conditions in developed countries, and their coexistence, especially among the elderly, poses notable diagnostic and therapeutic challenges. Notably, a considerable proportion of patients undergoing aortic valve replacement (AVR) present with concomitant CAD. Studies report that the prevalence of some degree of concomitant CAD in patients undergoing transcatheter aortic valve replacement (TAVR) varies widely, depending on patient risk profiles and the definitions used for CAD.¹⁾

Landmark trials illustrate this variability (Table 1).²⁾,³⁾,⁴⁾ The PARTNER 1A trial, targeting high-risk patients, reported a CAD prevalence of 74.9%,⁵⁾ while the PARTNER 3 and Evolut Low-Risk trials, which enrolled low-risk patients, reported notably lower rates.⁶⁾,⁷⁾ A joint statement by European Association of Percutaneous Cardiovascular Interventions and European Society of Cardiology (ESC) estimates CAD in about half of TAVR patients, noting that prevalence decreases in younger, lower-risk individuals.⁸⁾ This trend may partly reflect not only the healthier baseline characteristics of low-risk patients but also selective exclusion of those with complex CAD—such as high SYNTAX scores or multivessel disease—in low-risk trials. Therefore, reported CAD prevalence in such trials may underestimate its true burden in clinical practice, suggesting real-world registries could reveal greater CAD complexity.

Table 1. Prevalence of coronary artery disease in pivotal aortic stenosis intervention trials.

Trial name	Patient risk profile	Definition of CAD used (if specified)	Prevalence of any CAD (%)	Prevalence of prior PCI (%)	Prevalence of prior CABG (%)
PARTNER 1A (TAVR arm)5)	High	Not specified in summary	74.9	Not specified	Not specified
PARTNER 1B (TAVR arm)2)	Extreme (inoperable)	Any CAD	67.6	30.5	37.4
PARTNER 2 (TAVR arm)3)	Intermediate	Significant CAD (≥70% stenosis in ≥1 major epicardial artery or ≥50% LM)	69.2	27.1	23.6
PARTNER 3 (TAVR arm)6)	Low	Documented CAD	27.7	-	-
Evolut Low Risk (TAVR)7)	Low	History of PCI/CABG	Not directly stated	14.2	2.5
SURTAVI (TAVR arm)4)	Intermediate	Angiographically significant CAD (≥50% LM or ≥70% other)	62.6	21.3	16.0

CAD definitions and reported metrics can vary between trials. “Any CAD” may include non-obstructive disease.

AS = aortic stenosis; CABG = coronary artery bypass grafting; CAD = coronary artery disease; LM = left main; PCI = percutaneous coronary intervention; TAVR = transcatheter aortic valve replacement.

The pathophysiological interaction between severe AS and CAD creates a synergistic burden that accelerates left ventricular (LV) dysfunction and adverse clinical outcomes. AS-induced pressure overload promotes ventricular hypertrophy, while concurrent CAD compounds myocardial ischemia, together accelerating heart failure progression. The overlapping symptomatology of AS-related demand ischemia and epicardial coronary disease further complicates clinical assessment and symptom attribution.

As TAVR expands to younger, lower-risk populations, the management paradigm becomes increasingly complex. While TAVR offers immediate procedural advantages, the limited long-term durability data for transcatheter heart valves (THVs) beyond 10–15 years creates a treatment paradox. This uncertainty necessitates careful consideration of future coronary access, repeat intervention feasibility, and potential surgical THV explantation. Therefore, optimal management requires integrating both immediate procedural risks and long-term prognostic factors, including CAD progression and reintervention strategies, within an individualized treatment framework.

DIAGNOSTIC EVALUATION OF CORONARY ARTERY DISEASE IN PATIENTS WITH SEVERE AORTIC STENOSIS

Accurate CAD diagnosis is essential for AS patients considering AVR, requiring a balance between comprehensive assessment and procedural risk based on individual patient factors.

Role of invasive coronary angiography

Invasive coronary angiography remains the gold standard for anatomical assessment of CAD in candidates for both TAVR and surgical aortic valve replacement (SAVR).⁸⁾ The 2021 ESC/European Association for Cardio-Thoracic Surgery (EACTS) guidelines recommend coronary angiography prior to valve surgery in patients with severe valvular heart disease who have cardiovascular history, suspected ischemia, LV dysfunction, or established risk factors, including age over 40 in men and postmenopausal status in women.⁹⁾ However, coronary angiography entails procedural risks, particularly in elderly and frail patients with AS. Moreover, the interpretation of angiographic stenosis severity can be complicated by the unique physiological milieu created by severe AS. Consequently, there is increasing interest in adjunctive physiological assessments and non-invasive imaging modalities.

Non-invasive assessment: coronary computed tomography angiography and computed tomography-derived fractional flow reserve

Coronary computed tomography angiography (CCTA) has gained recognition as a valuable non-invasive modality in the assessment of patients with severe AS, particularly in the context of TAVR. Beyond its established role in evaluating the aortic annulus, root anatomy, and vascular access routes, CCTA enables concurrent coronary artery assessment, offering a potential “one-stop” diagnostic approach.¹⁾ Reflecting this utility, the 2021 ESC/EACTS guidelines suggest that CCTA may be considered in lieu of invasive coronary angiography in patients with severe valvular heart disease and low pre-test probability of CAD, thereby potentially minimizing procedural risk and expediting TAVR workflows.⁹⁾

The diagnostic capabilities of CCTA have been enhanced by computed tomography (CT)-derived fractional flow reserve (CT-FFR), which uses computational modeling to non-invasively estimate lesion-specific ischemia.¹⁰⁾ Preliminary evidence, including the CAST-FFR study,¹¹⁾ supports the feasibility of CT-FFR in selected populations, but these early studies largely excluded patients with prior coronary interventions, left main (LM) disease, or reduced LV function. Moreover, the high coronary artery calcium burden frequently renders CT scans unsuitable for reliable assessment and substantially impairs CT-FFR accuracy. Given these significant limitations, CT-FFR should currently be regarded as a research tool requiring extensive further validation rather than a clinically ready diagnostic modality. Therefore, invasive coronary angiography remains the necessary standard for assessing CAD in patients with severe AS.

Fractional flow reserve and instantaneous wave-free ratio: utility and limitations in severe aortic stenosis

FFR and instantaneous wave-free ratio (iFR) are widely used to guide percutaneous coronary intervention (PCI) for intermediate coronary lesions. However, their reliability in patients with severe AS remains uncertain due to altered hemodynamics. Severe AS is characterized by increased LV afterload, compensatory hypertrophy, and reduced coronary flow reserve, all of which may affect both the induction of hyperemia and the physiological response measured by FFR.¹⁰⁾ Consequently, standard FFR thresholds may underestimate lesion severity in this population. Guidelines reflect these concerns. While the 2020 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines support the use of conventional iFR (≤0.89) and FFR (≤0.80) thresholds,¹²⁾ the 2021 ESC/EACTS guidelines caution that these cutoffs have not been validated in AS and advise careful interpretation.⁹⁾

Evidence on the effects of AVR on physiological indices is mixed (summarized in Table 2). For example, Pesarini et al.¹³⁾ reported no significant overall change in FFR values immediately after TAVR. However, a differential effect was observed: FFR in lesions initially deemed ischemic (FFR ≤0.80) tended to worsen (decrease further), whereas FFR in initially non-ischemic lesions (FFR >0.80) tended to improve. Ultimately, only 6% of lesions crossed the diagnostic FFR cutoff of 0.80 post-TAVR, leading the authors to conclude that while FFR variations occur, they are generally minor, though borderline lesions might become functionally significant after valve replacement.¹³⁾

Table 2. Invasive physiological assessment (FFR/iFR/RFR) in severe aortic stenosis.

Study	Patient population (number of AS severity)	Index (cutoff)	Key findings pre-AVR	Key findings post-AVR (acute/long-term)	Proposed AS-specific cutoffs	Diagnostic accuracy (vs. ischemia standard)	Key conclusions
Pesarini et al. (2016)13)	54 patients (133 lesions), severe AS	FFR (≤0.80)	-	No significant overall FFR change. FFR worsened in initially positive lesions (0.71 to 0.66); improved in initially negative lesions (0.92 to 0.93). The 6% of lesions crossed 0.80 cutoff.	Not proposed	Not specified	FFR variations minor; borderline lesions might become significant post-TAVI.
Minten et al. (2024)14)	6 studies (147 lesions for FFR, 105 for NHPR immediate; 93 FFR, 68 NHPR long-term), severe AS	FFR (≤0.80), NHPR (iFR/RFR ≤0.89)	-	Immediate: FFR decreased (−0.013), NHPR stable.	Not proposed	Not specified	FFR might underestimate, NHPRs might overestimate pre-TAVR lesion significance. Changes clinically relevant mainly for borderline lesions.
				Long-term: FFR decreased (−0.023), NHPR increased non-significantly.
Minten et al. (2025)15)	116 patients (146 lesions), severe AS & CAD	FFR (≤0.80), RFR (≤0.89)	High FFR/RFR discordance (FFR-neg/RFR-pos: 42.3%).	Acute: FFR decreased, RFR stable.	FFR ≤0.83, RFR ≤0.85	75–80% accuracy (vs. SPECT)	Standard FFR/RFR cutoffs may not be optimal. AS-specific cutoffs appear more accurate.
				6 months: FFR further decreased, RFR increased.
				21.5% FFR, 39.8% RFR lesions crossed cutoffs.
Jo et al. (2024)16)	227 patients (335 lesions), severe AS	FFR (≤0.80), iFR (≤0.89)	iFR-positive discordance (24.2%) more prevalent.	iFR ≤0.89 not prognostic for deferred lesion failure; FFR ≤0.80 was.	Not proposed	iFR accuracy poor for predicting FFR ≤0.80 in severe obstructions	iFR may overestimate functional severity in severe AS; FFR seems less affected.

AS = aortic stenosis; AVR = aortic valve replacement; CAD = coronary artery disease; FFR = fractional flow reserve; iFR = instantaneous wave-free ratio; NHPR = non-hyperemic pressure ratio; RFR = resting full-cycle ratio; SPECT = single-photon emission computed tomography; TAVI = transcatheter aortic valve implantation; TAVR = transcatheter aortic valve replacement.

More recent data paint a nuanced picture. A 2024 meta-analysis published in J Am Heart Assoc ¹⁴⁾ found that immediately after TAVR, FFR values decreased significantly (mean change: −0.0130), while non-hyperemic pressure ratios (NHPRs, such as iFR/resting full-cycle ratio [RFR]) remained stable. In the longer term (median 6 months), FFR values showed a further significant decrease (mean change: −0.0230), whereas NHPRs exhibited a non-significant increase. The authors concluded that, using standard cutoffs, FFR might underestimate the physiological significance of a coronary lesion pre-TAVR, while NHPRs might overestimate its significance. These changes were deemed clinically relevant primarily for borderline lesions, suggesting that clearly positive or negative physiological assessments pre-TAVR could still be trusted.

Adding to this complexity, a recent study observed a high rate of FFR/RFR discordance pre-AVR, with 42.3% of lesions being FFR-negative (FFR >0.80) but RFR-positive (RFR ≤0.89). Acutely after AVR, FFR decreased while RFR remained stable. However, at 6 months post-AVR, FFR had decreased further, whereas RFR had increased significantly. This study proposed AS-specific ischemia cutoffs of FFR ≤0.83 and RFR ≤0.85, which demonstrated comparable diagnostic accuracy of 75–80% against myocardial perfusion imaging.¹⁵⁾ However, these thresholds remain exploratory and require further prospective validation. In contrast, another study found that in severe AS, an iFR ≤0.89 had no prognostic value for deferred lesion failure, whereas an FFR ≤0.80 did. This study reported a high prevalence of iFR-positive discordance (iFR ≤0.89 and FFR >0.80) at 24.2%, which was not associated with worse outcomes, leading to the conclusion that iFR may overestimate lesion severity in AS.¹⁶⁾

The high discordance rates between FFR and iFR/RFR in severe AS patients imply that neither index can be considered independently reliable in this specific population. FFR’s reliance on achieving maximal hyperemia can be problematic in AS due to blunted vasodilator response. Resting indices like iFR/RFR, while theoretically less affected by global hemodynamic changes, have also shown variability post-AVR and potential for misclassification.¹⁷⁾ This suggests that treatment decisions should not hinge solely on one physiological measure with standard thresholds. Furthermore, it must be emphasized that AS-specific cutoffs for FFR/iFR are currently investigational and have not been validated in large-scale trials for routine clinical use. A more holistic approach, integrating angiographic findings, symptom status, and non-invasive imaging data remains essential. For lesions where revascularization is deferred, post-TAVR physiological reassessment becomes critically important, provided that coronary access is not compromised.

REVASCULARIZATION STRATEGIES FOR CORONARY ARTERY DISEASE IN SEVERE AORTIC STENOSIS

The decision to revascularize concomitant CAD in patients undergoing AVR for severe AS is multifaceted, involving consideration of lesion severity, patient risk, procedural choice for valve replacement (SAVR or TAVR), and the overall goals of treatment.

Indications for revascularization: guideline perspectives

Current guidelines from leading cardiovascular societies offer structured recommendations for managing CAD in patients with severe AS undergoing valve intervention (Table 3). The 2021 ESC/EACTS guidelines advocate coronary artery bypass grafting (CABG) during SAVR for stenoses ≥70%, with consideration at ≥50% for LM disease.⁹⁾ In the TAVR setting, PCI is considered for proximal lesions exceeding 70% stenosis.

Table 3. Guideline recommendations for CAD revascularization in patients with severe aortic stenosis undergoing valve intervention.

Guideline	Recommendation for CAD assessment	Threshold for revascularization	Preferred revascularization strategy with SAVR	Preferred/considered revascularization strategy with TAVR	Class of recommendation & level of evidence (selected examples)	Key caveats/notes
2021 ESC/EACTS VHD9)	ICA recommended (risk factor based). CCTA alternative if low CAD probability.	CABG: ≥70% stenosis (≥50% for LM). PCI (TAVR): >70% proximal stenosis.	CABG	PCI	CABG with SAVR for ≥70% stenosis: Class I, LOE B.	FFR/iFR utility not well established in AS; caution with FFR 0.80 in AS.
					PCI with TAVR for >70% proximal stenosis: Class IIa, LOE C.
2020 ACC/AHA VHD12)	ICA generally recommended pre-AVR. CCTA may be alternative for low-risk CAD.	SAVR+CABG: Significant CAD (≥50% LM, ≥70% other major epicardials). TAVR+PCI: Significant proximal CAD.	CABG	PCI	SAVR+CABG for significant CAD: Class I, LOE B-NR.	Shared decision-making and Heart Team evaluation are crucial. Considers patient risk, CAD complexity (SYNTAX score), and completeness of revascularization.
					PCI with TAVR for significant CAD: Class IIa, LOE B-NR (if TAVR appropriate).
2023 AHA/ACC CCD (referencing VHD/Revascularization Guidelines)18)	Per 2020 VHD Guideline for assessment at time of valve intervention.	Per 2020 VHD Guideline.	Per 2020 VHD Guideline.	Per 2020 VHD Guideline. DAPT per 2021 Revascularization Guideline post-PCI/TAVR.	Refers to primary VHD/Revascularization Guidelines.	Focuses on chronic management post-intervention or if no intervention.

This table provides a general summary. Specific recommendations, class of recommendation/LOE may vary based on detailed clinical scenarios within the full guideline documents. LOE B-NR indicates evidence derived from non-randomized studies, as classified by the ACC/AHA grading system.

ACC = American College of Cardiology; AHA = American Heart Association; AS = aortic stenosis; AVR = aortic valve replacement; CABG = coronary artery bypass grafting; CAD = coronary artery disease; CCD = chronic coronary disease; CCTA = coronary computed tomography angiography; DAPT = dual antiplatelet therapy; EACTS = European Association for Cardio-Thoracic Surgery; ESC = European Society of Cardiology; FFR = fractional flow reserve; ICA = invasive coronary angiography; iFR = instantaneous wave-free ratio; LM = left main; LOE = level of evidence; PCI = percutaneous coronary intervention; SAVR = surgical aortic valve replacement; STS = Society of Thoracic Surgeons; TAVR = transcatheter aortic valve replacement; VHD = valvular heart disease.

The 2020 ACC/AHA guideline on valvular heart disease offers more granular recommendations, designating separate sections for CAD management in SAVR (14.1.2) and TAVR (14.1.1).¹²⁾ It emphasizes individualized decision-making through Heart Team discussions. In patients undergoing TAVR, PCI is considered reasonable for significant proximal CAD, particularly if it is extensive or involves the LM artery, though the evidence base is less robust and timing is a key consideration.

The 2023 AHA/ACC guideline for the management of patients with chronic coronary disease explicitly refers clinicians to the 2020 valvular heart disease guideline for decisions regarding CAD management at the time of valve intervention.¹⁸⁾ It also directs to the 2021 ACC/AHA/SCAI guideline for guidance on dual antiplatelet therapy (DAPT) in patients with severe AS and concomitant CAD who undergo PCI and TAVR.¹⁹⁾ This hierarchical organization of guidance reflects the complexity of managing CAD in severe AS.

While these guidelines share fundamental principles regarding revascularization in severe AS, important nuances distinguish European and American approaches. The key differences center on the strength of recommendations for physiological assessment and revascularization thresholds, reflecting divergent philosophies in managing diagnostic uncertainty. ESC/EACTS guidelines provide stronger endorsement for FFR/iFR use with a Class IIa recommendation (“should be considered”) compared to ACC/AHA’s more cautious Class IIb (“may be considered”), despite both acknowledging the limitations of physiological assessment in altered hemodynamics of severe AS. For anatomical decision-making, ESC/EACTS guidelines adopt a more prescriptive approach, specifically recommending PCI for proximal stenoses ≥70% in TAVR patients (Class IIa), while ACC/AHA guidelines deliberately avoid rigid angiographic cutoffs and instead emphasize individualized physiological assessment through their Class IIb recommendation. This divergence reflects the European preference for standardized, protocol-driven approaches versus the American emphasis on clinical discretion and case-by-case evaluation. Notably, both frameworks converge on the critical importance of multidisciplinary Heart Team decision-making, providing their strongest Class I recommendation for this collaborative approach as the foundation of optimal patient care.

Medical management of coronary artery disease in transcatheter/surgical aortic valve replacement candidates

Optimal medical therapy (OMT) for CAD serves as the baseline against which revascularization strategies are evaluated. For patients with severe AS and non-severe, asymptomatic CAD or those at very high procedural risk, managing coronary disease with OMT alone while proceeding with AVR represents a critical application of shared decision-making. This approach requires comprehensive Heart Team discussions that move beyond clinical risk-benefit calculations to address what matters most to the patient. In frail individuals, the conversation must explicitly acknowledge that additional interventions can trigger cascades of adverse events—delirium, functional decline, and loss of independence—that patients often fear more than death itself. The shared decision-making process should evolve into deliberate “goal talks” to clarify whether priorities center on prolonging life versus maintaining independence, preserving cognitive function, and minimizing treatment burden.

This patient-centered approach aligns with evidence from randomized trials in chronic coronary syndromes without AS, which have not consistently demonstrated mortality benefits from PCI over OMT. Accordingly, PCI in AS is typically symptom-directed, reserved for refractory angina despite AVR and OMT. Deferring PCI until after TAVR offers additional advantages: reduced peri-procedural bleeding risks from DAPT (particularly valuable in elderly, frail populations), avoidance of unreliable pre-TAVR physiological assessments, and opportunity for accurate lesion reassessment in a stable post-TAVR state. This “TAVR-first, deferred-PCI” strategy becomes highly attractive when post-TAVR coronary access is preserved through careful valve selection and commissural alignment.

Percutaneous coronary intervention versus coronary artery bypass grafting in the context of aortic valve replacement

The decision between a percutaneous strategy (PCI with TAVR) and a surgical approach (CABG with SAVR) in patients with severe AS and coexisting CAD is primarily guided by the complexity of CAD, the patient’s surgical risk, and the objective of achieving complete and lasting revascularization.

According to current ACC/AHA guidelines, SAVR combined with CABG is generally favored in cases of complex CAD, such as bifurcation left main disease or extensive multivessel involvement, especially with a high SYNTAX score (>33).¹²⁾ In contrast, PCI may be a suitable alternative for anatomically simpler disease, including isolated significant left main stenosis or single proximal vessel involvement. The 2021 ESC/EACTS guidelines echo this approach, recommending SAVR when multivessel CAD necessitates surgical revascularization.⁹⁾ For patients at elevated surgical risk—typically defined by an Society of Thoracic Surgeons predicted risk of mortality >8%—TAVR with PCI is often preferred, even if it entails incomplete revascularization.

The underlying rationale for favoring SAVR+CABG in patients with complex CAD stems from the extensive body of evidence supporting the long-term benefits of surgical revascularization, especially when utilizing arterial grafts. CABG often allows for more complete revascularization and has demonstrated superior long-term durability and freedom from repeat intervention compared to multivessel PCI in numerous trials conducted outside the specific context of AS.²⁰⁾ When a patient requires AVR, the opportunity to perform concomitant CABG addresses both the valvular and complex coronary pathologies in a single, definitive surgical setting, potentially offering better long-term coronary outcomes.

However, this potential for superior long-term coronary benefit must be carefully weighed against the higher immediate procedural risk associated with combined SAVR+CABG compared to a fully percutaneous approach with TAVR+PCI. Combined major cardiac surgery is inherently more invasive and carries a higher upfront risk of mortality and significant morbidity (e.g., stroke, bleeding, prolonged recovery), particularly in elderly, frail, or comorbid patients.²¹⁾ The Heart Team, therefore, faces the critical task of balancing the long-term advantages of surgical coronary revascularization against the short-term procedural risks of a combined operation versus a less invasive percutaneous strategy. This balance is dynamic and shifts based on individual patient characteristics, including overall surgical risk, the precise nature and extent of CAD, and life expectancy.

TIMING OF PERCUTANEOUS CORONARY INTERVENTION IN PATIENTS UNDERGOING TRANSCATHETER AORTIC VALVE REPLACEMENT

The optimal timing of PCI in patients with severe AS and concomitant CAD who are candidates for TAVR remains a subject of ongoing debate and research. Clinical practice varies, with PCI being performed before TAVR, concomitantly with TAVR in a single procedure, or as a staged procedure after TAVR. Each approach has theoretical advantages and disadvantages, and current evidence, including results from randomized controlled trials (RCTs) and observational studies, provides a complex picture (Table 4).

Table 4. Summary of randomized controlled trials and major registries on PCI timing in TAVR.

Trial/registry name (author, year)	Study design	Patient population (number of CAD definition, AS severity)	Intervention arms	Primary endpoint	Key efficacy outcomes (MACE, MI, revascularization)	Key safety outcomes (mortality, stroke, bleeding)	Follow-up duration	Main conclusions
ACTIVATION (Patterson et al., 2021)22)	RCT (terminated early)	n=235; Severe AS; Significant CAD (>70% or >50% LM/graft); CCS ≤2 angina	PCI pre-TAVR vs. No PCI pre-TAVR (OMT)	1-year death or rehospitalization	Similar rates (41.5% PCI vs. 44.0% no PCI). Non-inferiority not met.	Similar mortality (13.4% PCI vs. 12.1% no PCI). Higher bleeding with PCI (p=0.021).	1 year	Similar death/rehospitalization; PCI resulted in higher bleeding.
NOTION-3 (Lønborg et al., 2024)23)	RCT	n=455; Severe AS; Significant CAD (FFR ≤0.80 or ≥90% stenosis; low complexity; no LM)	PCI (mostly pre-TAVR) vs. conservative treatment	MACE (death, MI, urgent revascularization)	Lower MACE with PCI (26% vs. 36%; HR, 0.71). Lower MI (7% vs. 14%) & urgent revascularization (2% vs. 11%) with PCI. Benefit after 1 year.	No difference in mortality. Higher bleeding with PCI (28% vs. 20%; HR, 1.51).	Median 2 years	PCI for significant CAD pre-TAVR reduced MACE, driven by MI/urgent revascularization, but increased bleeding.
REVASC-TAVI registry (Rheude et al., 2023)25)	Observational registry	n=1,603; Severe AS; Stable CAD	PCI before TAVR vs. PCI concomitant with TAVR vs. PCI after TAVR	All-cause death; Composite (death, stroke, MI, CHF rehospitalization)	PCI after TAVR: Lower all-cause death (6.8% vs. 20.1% [pre] vs. 20.6% [concomitant]). Lower composite endpoint (17.4% vs. 30.4% [pre] vs. 30.0% [concomitant]).	Not detailed for specific timings.	2 years	PCI after TAVR associated with improved 2-year clinical outcomes compared to other timings.
Meta-analysis (Wang et al., 2025)26)	Meta-analysis (23 studies)	n=15,812; TAVI with concomitant CAD	PCI pre/concomitant TAVI (PCI-TAVI) vs. TAVI alone; PCI-TAVI vs. PCI after TAVI (TAVI-PCI)	All-cause mortality (short, mid, long-term)	PCI-TAVI vs. TAVI alone: No difference short/mid-term mortality; Higher long-term mortality with PCI-TAVI (RR, 1.20). TAVI-PCI vs. PCI-TAVI: Lower short-term (RR, 5.41 for PCI-TAVI) & long-term (RR, 2.92 for PCI-TAVI) mortality with TAVI-PCI.	Not primary focus.	Varied (short, mid, long-term)	PCI pre/concomitant with TAVI may not offer benefit, potentially worse long-term. PCI after TAVI associated with improved outcomes.
CathPCI registry (Lalani et al., 2025)27)	Observational registry (Medicare + CathPCI)	n=52,780 TAVR (Medicare); n=1,309 post-TAVR PCI vs. 5,236 matched non-TAVR PCI (CathPCI)	PCI post-TAVR vs. PCI in non-TAVR patients	Procedural success, complications, long-term outcomes	Incidence of PCI post-TAVR: 5.1% at 5 years. Procedural success similar.	Post-TAVR PCI: Longer fluoroscopy time, higher post-procedure stroke (0.8% vs. 0.4%) & bleeding (5.1% vs. 2.9%). Long-term (3 years): Higher repeat PCI, stroke, death vs. non-TAVR PCI.	Up to 5 years (Medicare); 3 years (CathPCI)	PCI post-TAVR feasible but associated with higher complications and worse long-term outcomes compared to PCI in non-TAVR patients.
Observational study (Dhoble et al., 2025)24)	Observational (propensity matched)	n=51,480 total; propensity-matched cohort of 12,936. Patients had stable CAD and underwent TAVR with a SAPIEN 3 balloon-expandable valve.	PCI within 90 days before TAVR vs. concomitant PCI with TAVR	All-cause mortality, stroke, and a composite of mortality and stroke at 3 years	Composite of mortality and stroke at 3 years was higher in the concomitant group (43.5% vs. 42.8%; p=0.012). Periprocedural MI was higher in the concomitant group (1.5% vs. 0.1%). No significant difference in functional status (KCCQ score) improvement at 1 year.	Concomitant PCI had higher major vascular complications (2% vs 1.4%), higher 30-day life-threatening bleeding (1.9% vs 1.0%), higher need for a new permanent pacemaker (10.8% vs. 8.7%), and slightly higher 3-year mortality (38.8% vs. 38.1%). 3-year stroke rates were similar.	Up to 3 years	In patients undergoing TAVR with a balloon-expandable valve, concomitant PCI was associated with higher major vascular complications and a slightly higher rate of the composite of mortality and stroke at 3 years compared to undergoing PCI within the 90 days before TAVR.

AS = aortic stenosis; CAD = coronary artery disease; CCS = Canadian Cardiovascular Society; CHF = congestive heart failure; CI = confidence interval; FFR = fractional flow reserve; HR = hazard ratio; KCCQ = Kansas City Cardiomyopathy Questionnaire; LM = left main; MACE = major adverse cardiovascular events; MI = myocardial infarction; OMT = optimal medical therapy; PCI = percutaneous coronary intervention; RCT = randomized controlled trial; RR = risk ratio; TAVI = transcatheter aortic valve implantation; TAVR = transcatheter aortic valve replacement.

Percutaneous coronary intervention prior to transcatheter aortic valve replacement

Performing PCI in a staged manner before the TAVR procedure has been a traditional approach, often favored due to concerns about potential hemodynamic instability and ischemic complications during TAVR (e.g., during rapid ventricular pacing) if significant CAD is left untreated. Another rationale has been the anticipated difficulty of coronary re-access after THV implantation.¹⁾

The ACTIVATION trial was an RCT designed to address this strategy. It randomized 235 patients with severe AS, significant CAD, and Canadian Cardiovascular Society (CCS) class ≤2 angina to either pre-TAVR PCI or no PCI (medical management of CAD).²²⁾ The primary endpoint was a composite of all-cause death or rehospitalization at 1 year. The trial, which was terminated early due to slow recruitment, found no significant difference in the primary endpoint: 41.5% in the PCI arm versus 44.0% in the no-PCI arm. The prespecified non-inferiority margin was not met. Notably, the PCI arm experienced a significantly higher rate of any bleeding complications. The investigators concluded that while rates of death and rehospitalization were similar, pre-TAVR PCI did not demonstrate non-inferiority and resulted in increased bleeding.

In contrast, the NOTION-3 trial, another RCT, enrolled 455 patients with severe AS and significant CAD (defined by FFR ≤0.80 or ≥90% diameter stenosis, excluding LM disease and complex lesions) undergoing TAVR.²³⁾ Patients were randomized to PCI (predominantly pre-TAVR) or conservative medical treatment for their CAD. Over a median follow-up of 2 years, the primary composite endpoint of all-cause death, myocardial infarction (MI), or urgent revascularization occurred in 26% of patients in the PCI group compared to 36% in the conservative treatment group (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.51–0.99; p=0.04). This benefit was primarily driven by a reduction in MI and urgent revascularization in the PCI group and became apparent only after the first year of follow-up. However, consistent with ACTIVATION trial, PCI was associated with a higher risk of bleeding events (28% vs. 20%; HR, 1.51).

The divergence in findings between the ACTIVATION and NOTION-3 trials may be attributable to several factors, including differences in patient populations, definitions of significant CAD, and statistical power. ACTIVATION trial included a larger proportion of patients with minimal or no angina and defined CAD primarily by angiography, whereas NOTION-3 utilized stricter physiological (FFR-based) or high-grade angiographic criteria, potentially selecting for more hemodynamically significant lesions. The delayed emergence of benefit in NOTION-3 lends credence to the hypothesis that TAVR may “unmask” underlying CAD; as AS symptoms resolve and patients become more physically active, pre-existing coronary lesions may become clinically manifest if left untreated. However, the consistent finding of increased bleeding risk with pre-TAVR PCI in both trials, predominantly attributed to the need for DAPT, is a critical consideration. This suggests that routine pre-TAVR PCI for all angiographically intermediate CAD is likely not justified. A more selective approach, perhaps targeting only high-grade, physiologically significant lesions, particularly if extensive or clearly symptomatic, might be beneficial, but this must be carefully weighed against the increased bleeding hazard. The “unmasking” phenomenon also provides a rationale for considering a deferred PCI strategy if the CAD is not immediately life-threatening and post-TAVR coronary access is anticipated to be feasible.

Concomitant percutaneous coronary intervention and transcatheter aortic valve replacement (single procedure)

Performing PCI and TAVR during the same hospitalization, often in the same procedural setting, offers the allure of patient convenience by consolidating interventions into a single admission and potentially reducing overall length of stay and costs. However, this approach also presents challenges. Concomitant procedures can lead to prolonged procedural times, increased exposure to contrast media (risking contrast-induced nephropathy), and more complex management of antithrombotic therapy, especially if the TAVR component is complicated by vascular injury requiring immediate attention while the patient is on potent antiplatelet agents for the fresh coronary stent.¹⁾

Observational data on the outcomes of concomitant PCI and TAVR have been conflicting, with some studies suggesting no significant increase in adverse events while others report higher rates of in-hospital mortality or complications such as acute kidney injury. A recent analysis focusing on patients receiving the SAPIEN 3 THV between 2015 and 2023, compared outcomes of concomitant PCI+TAVR (13.9% of the cohort) with staged PCI performed up to 90 days before TAVR (84.7%).²⁴⁾ After propensity matching, the concomitant PCI+TAVR group was found to have significantly higher rates of in-hospital mortality, 30-day mortality, cardiac death, stroke, major vascular complications, life-threatening bleeding events, need for dialysis, and permanent pacemaker implantation. While the authors acknowledged that patients selected for concomitant procedures tended to present with worse symptoms, which might not be fully accounted for by propensity matching, these findings raise significant safety concerns.

The convenience for the patient must be rigorously weighed against these potentially increased acute risks. The heightened risk of bleeding complications when DAPT is initiated immediately before or during a TAVR procedure, particularly if vascular access issues arise, remains a paramount concern. Consequently, a staged approach—either performing PCI well in advance of TAVR or deferring PCI until after TAVR if the coronary lesions are not acutely critical—might offer a safer strategy for many patients. This allows for separation of the procedural stressors and enables more tailored and potentially de-escalated antithrombotic management around the TAVR itself. Concomitant PCI and TAVR should likely be reserved for highly selected cases, such as when PCI is anatomically straightforward and TAVR access is deemed very secure, or in situations where an unstable coronary lesion necessitates immediate intervention in a patient also requiring urgent TAVR.

Staged percutaneous coronary intervention after transcatheter aortic valve replacement

A strategy of performing TAVR first and then staging PCI for a later time if still indicated has several theoretical advantages. Once the aortic valve is replaced and hemodynamics are normalized, there is generally less risk of profound hemodynamic compromise during a subsequent PCI procedure. However, the primary and significant disadvantage of this approach is the potential difficulty in engaging the coronary ostia for subsequent angiography and intervention after THV implantation. The frame of the TAVR device, its implant depth, and its orientation relative to the native commissures and coronary ostia can create substantial technical challenges for coronary access, particularly with taller-frame valves or in cases of suboptimal commissural alignment.¹⁾

Despite these access concerns, some observational studies and meta-analyses have suggested that performing PCI after TAVR may be associated with more favorable clinical outcomes compared to strategies involving PCI before or concomitantly with TAVR. For instance, the REVASC-TAVI registry reported that PCI performed after TAVR was associated with improved 2-year clinical outcomes.²⁵⁾ A recent systematic review and meta-analysis further supports this, finding that PCI after TAVR (transcatheter aortic valve implantation [TAVI]-PCI) was associated with lower rates of all-cause mortality at both short-term and long-term follow-up compared to PCI performed before or concomitantly with TAVR (PCI-TAVI).²⁶⁾ This could be due to more accurate lesion assessment post-AS relief, avoidance of DAPT-related complications during the TAVR hospitalization, or selection bias where more stable patients are chosen for a deferred strategy.

Conversely, data from the NCDR CathPCI Registry provide a more sobering perspective on PCI performed after TAVR when compared to PCI in a non-TAVR population.²⁷⁾ In this registry analysis of Medicare patients undergoing TAVR between 2011 and 2017, the incidence of PCI was 5.1% at 5 years post-TAVR. While procedural success rates for PCI were similar between post-TAVR patients and propensity score-matched non-TAVR patients, those with a prior TAVR required longer fluoroscopy times and experienced higher rates of post-procedural stroke and bleeding. Over the long term (up to 3 years post-PCI), post-TAVR patients were more likely to undergo repeat PCI and had higher rates of stroke and death compared to their matched non-TAVR counterparts undergoing PCI. These findings suggest that the need for PCI after TAVR may mark a higher-risk population, and technical challenges of performing PCI through or around a THV frame may further compromise procedural safety.

Taken together, these observations underscore the complexity of procedural sequencing in patients with concomitant AS and CAD. While a “TAVR-first, PCI-if-needed” strategy may be favorable within the TAVR population, PCI after TAVR is not equivalent to PCI in native coronary settings. Therefore, careful pre-procedural planning—including implant techniques that preserve future coronary access—is essential. In patients with complex CAD or anticipated post-TAVR access difficulties, earlier revascularization (either pre-TAVR PCI or surgical AVR with CABG) should be considered by the Heart Team during initial strategy selection.

COMPARATIVE OUTCOMES: TRANSCATHETER AORTIC VALVE REPLACEMENT+PERCUTANEOUS CORONARY INTERVENTION VERSUS SURGICAL AORTIC VALVE REPLACEMENT+CORONARY ARTERY BYPASS GRAFTING

Comparing a fully percutaneous approach (TAVR+PCI) with a fully surgical approach (SAVR+CABG) for patients with severe AS and concomitant CAD is essential for informed decision-making, yet the evidence base is characterized by limited direct comparisons, particularly regarding long-term outcomes, and conflicting results between different study methodologies (Table 5). Many of the landmark TAVR versus SAVR trials specifically excluded patients with complex CAD requiring extensive revascularization, further complicating direct extrapolation.

Table 5. Comparative outcomes of TAVR+PCI versus SAVR+CABG for severe AS and CAD.

Study (author, year)	Study design	Patient population (number of risk profile, CAD complexity)	Follow-up duration	Primary endpoint	Mortality (all-cause, CV)	Stroke	MI	Repeat revascularization	Major bleeding	New pacemaker	Key PRO/QoL findings
TCW trial (Kedhi et al., 2025)21)	RCT (terminated early)	n=172; Severe AS & complex CAD (FFR-guided PCI)	1 year	Composite: Death, MI, disabling stroke, TVR, valve reintervention, severe bleeding	TAVR+PCI: 0% vs. SAVR+CABG: 10% (all-cause, p=0.0025)	TAVR+PCI: 1% vs. SAVR+CABG: 3% (disabling)	TAVR+PCI: 2% vs. SAVR+CABG: 1%	TAVR+PCI: 0% vs. SAVR+CABG: 1% (TVR)	TAVR+PCI: 2% vs. SAVR+CABG: 12% (life-threatening/disabling, p=0.01)	NS	NR
Cohort study (Jagadeesan et al., 2025)28)	Observational (Medicare data)	n=26,702 TAVR+PCI; n=17,250 SAVR+CABG (2018–2022)	Longitudinal (beyond index admission)	Not a single primary; multiple outcomes assessed	TAVR+PCI higher long-term all-cause mortality (HR, 1.09)	TAVR+PCI higher readmission for stroke (HR, 1.10)	TAVR+PCI higher MI (HR, 1.68)	Not specified for repeat revascularization specifically, but composite included valve reintervention	TAVR+PCI lower in-hospital (OR, 0.72)	TAVR+PCI higher in-hospital (OR, 1.59)	NR
SURTAVI sub-analysis (Søndergaard et al., 2019)29)	RCT sub-analysis	Low-intermediate risk, SYNTAX score ≤22	2 years	All-cause mortality or disabling stroke	No significant difference	No significant difference (part of primary endpoint)	NS	NS	NS	NS	NR
Multicenter study (Alperi et al., 2021)30)	Observational	n=800 (598 SAVR+CABG and 202 TAVR+PCI)	Median 3 years	MACCE	Similar rates	Similar rates	Similar rates	TAVR+PCI higher risk for repeat coronary revascularization	NS	NS	NR
Italian OBSERVANT study (Barbanti et al., 2018)31)	Observational	n=472 patients (236 per group after propensity-score matching)	3 years	Death, MI, stroke, unplanned revascularization	Comparable	Comparable	Comparable	Comparable (unplanned)	NS	NS	NR

This table summarizes key comparative studies. Definitions of endpoints and patient populations may vary. The TCW trial was terminated early.

AS = aortic stenosis; CABG = coronary artery bypass grafting; CAD = coronary artery disease; CI = confidence interval; CV = cardiovascular; FFR = fractional flow reserve; HR = hazard ratio; KCCQ = Kansas City Cardiomyopathy Questionnaire; MACCE = major adverse cardiovascular and cerebrovascular events; MI = myocardial infarction; NR = not reported; NS = not specified; OR = odds ratio; PCI = percutaneous coronary intervention; PRO/QoL = patient-reported outcomes/quality of life; RCT = randomized controlled trial; SAVR = surgical aortic valve replacement; STS = Society of Thoracic Surgeons; TAVR = transcatheter aortic valve replacement; TVR = target vessel revascularization.

Evidence from randomized trials and observational studies

The TCW trial represents one of the few RCTs directly comparing these comprehensive strategies.²¹⁾ This international, open-label, noninferiority trial randomized 172 patients with severe AS and complex CAD to either FFR-guided PCI plus TAVR or SAVR plus CABG. The trial was terminated prematurely after an interim analysis due to a significantly higher primary event rate in the surgical arm. At 12 months, the primary composite outcome—a composite of all-cause death, MI, disabling stroke, clinically driven target-vessel revascularization, valve reintervention, or life-threatening/disabling bleeding—occurred in 4% of patients in the TAVR+PCI arm compared to 23% in the SAVR+CABG arm (HR, 0.17; 95% CI, 0.06–0.51; p<0.001 for superiority). This striking difference was predominantly driven by a lower incidence of all-cause mortality (0% in TAVR+PCI vs. 10% in SAVR+CABG, p=0.0025) and life-threatening or disabling bleeding (2% vs. 12%, p=0.01) in the TAVR+PCI group.

However, these compelling findings from TCW trial are contrasted by recent large-scale observational data.²⁸⁾ While the TAVR/PCI group experienced lower in-hospital mortality, less major bleeding, and less acute kidney injury, they had a higher rate of new permanent pacemaker implantation. More critically, the longitudinal analysis revealed that TAVR/PCI was associated with higher risks of readmission for stroke, MI, all-cause mortality, and a composite of stroke, MI, valve reintervention, or death compared to SAVR/CABG.

Other evidence includes a sub-analysis of the SURTAVI trial, which focused on low-to-intermediate risk patients with SYNTAX scores ≤22.²⁹⁾ This analysis found no significant difference in the composite of all-cause mortality or disabling stroke at 2 years between patients undergoing TAVR+PCI and those undergoing SAVR+CABG. Broader systematic reviews and meta-analyses of available data, largely observational, have also yielded inconsistent results.³⁰⁾,³¹⁾,³²⁾ Some suggest that TAVR+PCI offers comparable rates of major adverse cardiovascular and cerebrovascular events at 3 years but may be associated with a higher risk of repeat coronary revascularization. Other analyses indicate potentially worse outcomes for TAVR+PCI, particularly when the underlying CAD is more complex.

The discrepancies between TCW and observational findings likely reflect differences in patient selection, CAD complexity, procedural completeness, and methodology. TCW utilized FFR guidance and a controlled RCT environment but had a limited sample size due to early termination, potentially exaggerating treatment effects. In contrast, real-world TAVR+PCI populations may include patients with higher baseline risk or unsuitable anatomy for surgery, confounding outcome comparisons. For patients with truly complex CAD (e.g., high SYNTAX score, LM trifurcation disease, extensive diffuse disease) who are otherwise good surgical candidates, SAVR+CABG may remain the preferred approach. This is supported by the proven long-term benefits of surgical revascularization in complex CAD and concerns from observational data about the durability of TAVR+PCI in such patients.

Bleeding and other procedural complications

Bleeding complications are a significant concern in this often elderly and frail patient population. The TCW trial reported a substantially lower rate of life-threatening or disabling bleeding with TAVR+PCI (2%) compared to SAVR+CABG (12%).²¹⁾ The observational analysis also found less major bleeding with TAVR+PCI.²⁸⁾ However, TAVR is consistently associated with a higher rate of new permanent pacemaker implantation compared to SAVR. Vascular complications, while generally decreasing with advancements in TAVR technology and operator experience, remain a consideration for the percutaneous approach. Paravalvular leak (PVL) is another TAVR-specific complication that, if more than mild, can adversely affect long-term outcomes, although rates of significant PVL have diminished with newer generation devices and improved implantation techniques. These procedural complications significantly impact patient recovery, hospital length of stay, and overall quality of life.

LIFETIME MANAGEMENT CONSIDERATIONS

The paradigm for managing patients with severe AS, particularly when concomitant CAD is present, is increasingly shifting towards a “lifetime management” perspective. This is especially pertinent with the expansion of TAVR indications to younger and lower-risk individuals who are likely to require further cardiovascular interventions over their lifespan. This long-term view necessitates careful consideration of initial treatment choices, valve durability, the implications for future coronary and valvular re-interventions, and robust shared decision-making processes.

Shared decision-making: integrating patient preferences, age, and life expectancy

Shared decision-making (SDM) is central to the management of severe AS. The 2020 ACC/AHA guidelines underscore that decisions regarding valve intervention should be guided by SDM, considering the patient’s expected longevity and the comparative risks and benefits of mechanical versus bioprosthetic valves.¹²⁾ In general, TAVR is preferred for individuals over 80 years of age or with a life expectancy under 10 years, whereas SAVR is favored in those younger than 65. For patients aged 65–80 or with an intermediate life expectancy (10–20 years), SDM is recommended.³³⁾

A 2022 expert consensus further highlights the need for a multidisciplinary Heart Team approach. The initial procedural choice carries significant lifetime implications, necessitating careful consideration of patient priorities, such as recovery trajectory, anticoagulation requirements associated with mechanical valves, likelihood of future interventions, and quality-of-life expectations. Effective SDM in this context hinges on the clinician’s ability to communicate not only established data but also areas of uncertainty. Key unknowns include the durability of TAVR devices beyond 10–15 years relative to surgical options, the risks associated with reinterventions (e.g., redo-TAVR, transcatheter aortic valve in surgical aortic valve [TAV-in-SAV], or TAVR explantation), and how the initial valve choice may affect future coronary access.³⁴⁾ Patients weigh surgical risks and reintervention needs differently, making structured decision tools essential. These tools support informed, patient-centered choices and help Heart Teams guide patients through complex treatment decisions, including those with limited evidence.

Valve durability: transcatheter aortic valve replacement versus surgical aortic valve replacement in the context of coronary artery disease

The long-term durability of the implanted aortic valve prosthesis is a critical determinant in lifetime management, particularly for younger patients who are expected to outlive their initial valve. Historically, mechanical valves used in SAVR offered excellent durability but necessitated lifelong anticoagulation with its attendant risks. Bioprosthetic surgical valves obviated the need for anticoagulation but had finite durability, leading to structural valve deterioration (SVD) over time. Advances in surgical bioprostheses, including novel tissue treatments (e.g., Edwards Inspiris Resilia) and designs (e.g., sutureless or rapid-deployment valves like Intuity or Perceval), aim to improve hemodynamics, reduce SVD, and extend durability.³⁵⁾

The advent of TAVR introduced THVs, whose long-term durability is still being established, especially in lower-risk, younger cohorts. The NOTION trial, which randomized lower-risk patients (mean age: ~79 years) to TAVR or SAVR, provided reassuring 10-year data, showing comparable clinical outcomes (all-cause mortality, stroke, MI).³⁶⁾ Notably, TAVR demonstrated better hemodynamic performance and a lower incidence of SVD at this time point, although it was associated with higher rates of permanent pacemaker implantation and paravalvular leakage compared to SAVR. Five-year data from the low-risk PARTNER 3 and Evolut Low Risk trials also showed TAVR to be comparable to SAVR for the composite endpoint of death or disabling stroke.³⁷⁾,³⁸⁾,³⁹⁾ However, some concerns have been raised from other datasets; for instance, one perspective on the PARTNER 2A trial (intermediate-risk patients) noted that the risk of stroke and death with TAVR eventually exceeded that with SAVR at the 5-year mark.⁴⁰⁾

However, these encouraging mid-term results must be interpreted with significant caution when extrapolating to younger patients. The pivotal low-risk trials primarily enrolled older patients (mean age: ~74 years), and their long-term data are subject to a profound survivorship bias, where many patients die from non-valvular causes before the prosthesis has had sufficient time to fail. Moreover, the impact of factors such as mild initial PVL, suboptimal THV hemodynamics due to misalignment, or patient-prosthesis mismatch (PPM) on valve function over 10–15 years or more in these younger individuals is largely unknown. Therefore, it must be clearly stated that the structural durability of current-generation THVs beyond 10 to 15 years in younger, lower-risk patients is not yet established. This significant knowledge gap mandates continued, rigorous long-term clinical and imaging surveillance to inform lifetime management strategies. The presence of concomitant CAD adds another layer of complexity, as the choice of valve and the initial intervention strategy can influence future management of coronary issues.

Planning for future interventions: coronary re-access and valve re-intervention

A cornerstone of lifetime management is anticipating and planning for future interventions. Coronary access after TAVR is a major concern. The design of the THV (frame height, cell size, leaflet position) and the specifics of its implantation (depth, commissural alignment) are critical determinants of whether future PCI will be straightforward or challenging.

Regarding valve re-intervention, failure of a surgical bioprosthesis can be managed by redo SAVR or by a TAV-in-SAV procedure. Redo SAVR is an established operation, though it carries higher risk than a primary SAVR.⁴¹⁾ TAV-in-SAV has become a common and often preferred less invasive option for failed surgical bioprostheses, particularly in higher-risk patients.³³⁾ Failure of an initial THV can be managed by surgical explantation of the TAVR device followed by SAVR, or by a TAV-in-TAV procedure. Surgical explantation is technically demanding and associated with significantly increased morbidity and mortality compared to redo SAVR after a primary SAVR, largely due to the incorporation of the THV stent frame into the aortic wall and surrounding tissues.⁴²⁾ Consequently, TAV-in-TAV is often seen as an attractive alternative if anatomically feasible. However, TAV-in-TAV procedures raise concerns about achieving an adequate effective orifice area (EOA) due to the progressive reduction in internal diameter with nested stents, potentially leading to PPM. They also further complicate coronary access and may increase the risk of sinus sequestration.⁴³⁾ Techniques such as bioprosthetic valve fracture (“cracking” the frame of the failed surgical or transcatheter valve) using an endovascular balloon can sometimes be employed to increase the annular dimensions and allow for implantation of a larger second valve, thereby mitigating PPM risk.⁴⁴⁾

The concept of a planned sequence of interventions emphasizes the necessity of a longitudinal treatment strategy rather than a singular procedural focus. Early procedural decisions, particularly valve selection and implantation technique, dictate the anatomical feasibility and clinical safety of subsequent interventions. Therefore, in younger patients or those with longer life expectancy, the Heart Team must deliberate whether initial SAVR, offering a more favorable structural foundation for future transcatheter options, may be preferable over a primary TAVR approach. This decision framework embodies a paradigm shift in valvular heart disease management, where procedural planning extends beyond the index intervention.

Strategies for younger, lower-risk patients with coexisting coronary artery disease

For younger, lower-risk patients who present with severe AS and significant, complex CAD (e.g., multivessel disease with a high SYNTAX score, or LM involvement that is amenable to CABG), an initial strategy of combined SAVR and CABG may offer the most robust long-term solution for both the valvular and coronary pathologies, despite the higher upfront procedural burden. This reasoning is based on several factors: CABG, particularly with extensive use of arterial conduits, generally provides more complete and durable revascularization for complex CAD compared to multivessel PCI, with established long-term benefits in terms of mortality and freedom from repeat revascularization.³²⁾ Surgical bioprosthetic valves have a well-documented track record of long-term durability, and should SVD occur, TAV-in-SAV is a well-established and often preferred re-intervention strategy.

Conversely, opting for an initial TAVR+PCI strategy in a younger patient with complex CAD might compromise future options. PCI for complex disease may be less durable than CABG, potentially necessitating repeat coronary interventions where access could be hampered by the previously implanted THV. Furthermore, future TAV-in-TAV procedures carry their own set of limitations regarding final EOA and coronary access, as discussed. Therefore, the Heart Team discussion should explicitly model these future scenarios and potential re-intervention pathways when advising these patients.

CORONARY ACCESS AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT

The ability to safely and effectively access the coronary arteries for diagnostic angiography or PCI at some point after the index TAVR procedure becomes a critical component of lifetime management.

Impact of transcatheter aortic valve replacement valve design and implantation technique

The intrinsic design of the THV plays a pivotal role. Key characteristics include the height of the stent frame, the size and geometry of the stent cells, the position of the leaflets (supra-annular versus intra-annular), and the overall bulk of the device within the aortic root.⁴⁵⁾ Shorter stent frames and THVs with larger, more open cell designs generally offer more favorable conditions for coronary access compared to taller-frame valves.⁴⁶⁾ For example, valves like the Edwards SAPIEN series, which are balloon-expandable and have a relatively short frame with large cells, are often associated with easier coronary access.⁴⁷⁾,⁴⁸⁾ In contrast, some self-expanding valves with taller frames and supra-annular leaflet positions can present greater challenges, as the catheter may need to be manipulated through the stent struts, and the upper portion of the valve frame may physically obstruct or hinder direct engagement of the coronary ostia.⁴⁹⁾ Intra-annular leaflet positioning tends to create less of a barrier compared to supra-annular designs where the leaflets and their supporting structures sit above the native annulus and closer to the coronary ostia.

The implantation depth of the THV is another critical factor. A THV implanted too high relative to the coronary ostia can directly impede access, especially with taller frame valves. Conversely, a very low implant might also pose challenges depending on the relationship between the THV sealing skirt and the ostia.

Anatomical factors of the native aortic root also interact with THV design. Low native coronary ostial height (typically defined as <12 mm from the annulus), narrow sinuses of Valsalva (<30 mm diameter), and bulky calcified native leaflets are recognized risk factors for acute coronary obstruction during the TAVR procedure itself.⁵⁰⁾ These same anatomical features can also make subsequent coronary access more difficult, as the THV frame and displaced native leaflets may crowd the already confined space around the ostia. A CT-based multivariate prediction model incorporating factors like native cusp height exceeding coronary ostial height, a virtual valve-to-coronary distance of ≤4 mm, or a culprit native leaflet calcium volume >600 mm³ has been developed to assess the risk of coronary obstruction during TAVR, and these parameters also inform the likelihood of future access challenges.⁵¹⁾

Given these multifactorial considerations, THV selection should not rely solely on short-term procedural metrics or hemodynamic efficacy. For patients with long life expectancy or concurrent but stable CAD, the coronary access profile of the implanted valve must be factored into the initial decision-making process. Strategic selection of THVs that are structurally conducive to future PCI is imperative and should be an integral component of multidisciplinary Heart Team discussions, particularly in cases where serial coronary interventions are anticipated.

The role of commissural alignment: techniques and outcomes

Commissural alignment refers to the intentional orientation of the THV commissural posts to align with the patient’s native aortic valve commissures. This practice, standard in SAVR, aims to create a more anatomical and physiological valve orientation. In the context of TAVR, achieving commissural alignment is increasingly recognized as important for optimizing future coronary access, and potentially for improving THV hemodynamics and long-term durability.⁵²⁾ Misaligned THV commissural posts can act as a physical barrier, directly overlying or hindering access to the coronary ostia.

The ALIGN-TAVR Consortium has been instrumental in advancing this field by providing standardized definitions for commissural alignment versus misalignment (e.g., aligned if within 0–15° deviation, with grades of mild, moderate, and severe misalignment beyond that) and for coronary overlap (angular distance from a THV post to a coronary ostium <15°).⁴⁶⁾ They have also described various implantation techniques to achieve better alignment with different commercially available THVs. These techniques often involve specific orientations of the delivery catheter system during insertion (e.g., flush port orientation for Evolut devices) and controlled rotational maneuvers performed under fluoroscopic guidance, frequently utilizing the “cusp-overlap” view (overlapping the right and left coronary cusps) to guide THV positioning relative to native landmarks.⁵³⁾ The ALIGN-ACCESS study demonstrated that achieving commissural alignment with supra-annular THVs improves the feasibility of selective coronary angiography post-TAVR.⁵⁴⁾

While the goal is often to align THV commissures with native commissures, the interplay with native aortic root anatomy, such as cusp asymmetry or eccentric coronary ostial positions, is crucial.⁵⁵⁾ If a coronary ostium is significantly eccentric relative to its native sinus or commissure, perfect commissural alignment of the THV might still result in a THV post obstructing that ostium. This has led to the concept of “coronary alignment,” which prioritizes positioning the THV commissures optimally relative to the coronary ostia themselves, even if this means deviating slightly from the native commissural positions.⁵⁶⁾ CT simulation studies suggest that while commissural alignment is generally effective in avoiding coronary overlap, coronary alignment might be preferred in specific cases of right coronary artery overlap or significant ostial eccentricity. This suggests that future alignment strategies may need to be highly individualized, using sophisticated pre-procedural CT planning and simulation to determine the patient-specific optimal THV orientation that balances anatomical commissural alignment (potentially beneficial for valve function and durability) with maximal coronary clearance. This might involve prioritizing one aspect over the other based on the individual’s coronary anatomy, CAD status, and anticipated future needs.

Strategies to preserve or facilitate future coronary access

Beyond achieving optimal commissural or coronary alignment, several other strategies during the index TAVR procedure can help preserve or facilitate future coronary access. These include valve selection, implant depth, anatomical risk factors, and leaflet modification techniques. Features such as low coronary takeoff, restricted sinus of Valsalva dimensions, or heavily calcified native leaflets are recognized predictors of post-TAVR coronary access difficulty. In such contexts, the Heart Team may consider selecting a THV system with proven compatibility in complex anatomies, adjusting implantation technique, or even revisiting the appropriateness of TAVR altogether when future coronary intervention is anticipated to be clinically imperative.

The development of dedicated tools and techniques for performing PCI in patients with existing THVs, alongside continued innovation in THV designs that inherently facilitate coronary access, will be as important as optimizing alignment during the index procedure. This includes specialized guide catheters, wires, and advanced imaging to navigate the THV frame. For instance, successfully engaging the coronary artery often requires downsizing catheters and employing a “wire-first” approach, where a hydrophilic wire is navigated through the valve frame to establish a rail for the guide catheter. In more challenging cases, advanced “air mailing” techniques may be necessary to access ostia with difficult take-offs.⁴⁷⁾,⁵⁷⁾

Once access is gained, achieving adequate support for device delivery is paramount. Guide extension catheters are indispensable, providing a protected and stable conduit through the valve frame to deliver stents and balloons, while mitigating the risk of stent damage from the valve’s struts.⁵⁷⁾ Techniques like the anchor balloon can provide additional stability when needed.⁵⁸⁾,⁵⁹⁾ Furthermore, meticulous catheter management is critical to avoid catastrophic complications such as guide catheter entrapment in the valve frame.⁶⁰⁾ A strict protocol, such as straightening the catheter with a guidewire before any withdrawal attempt, is essential for procedural safety, highlighting the need for a systematic and skilled approach to these complex interventions.⁴⁷⁾

CONCLUSION

The management of CAD in patients with severe AS is an intricate and dynamic field that mandates a highly individualized approach centered on a multidisciplinary Heart Team. Current best practices emphasize a meticulous evaluation of valvular and coronary disease complexity, patient-specific surgical risk, age, comorbidities, and patient preferences. The decision between a fully surgical (SAVR-CABG) versus a fully percutaneous (TAVR-PCI) strategy is largely dictated by the extent and complexity of CAD—with surgery often favored for patients with high SYNTAX scores—and the overall risk profile of the patient. As TAVR expands to younger, lower-risk populations, a paradigm shift towards “lifetime management” has become critical, placing greater emphasis on long-term valve durability and preserving future coronary access.

Despite recent advances in imaging, valve technology, and revascularization strategies, several unresolved questions continue to shape the evolving landscape of CAD management in patients with severe AS. These include the long-term durability of THVs in younger populations, the optimal timing and completeness of revascularization, and the validation of AS-specific thresholds for physiological lesion assessment. Emerging innovations such as next-generation THVs with improved coronary accessibility, artificial intelligence-driven procedural planning, and patient-specific 3-dimensional valve modeling offer promise for enhancing future outcomes. Large-scale, prospective trials with extended follow-up and inclusion of patient-reported outcomes will be essential to refine clinical decision-making and optimize lifetime management strategies in this complex cohort.