Interventional treatment options for elderly patients with mitral regurgitation

ABSTRACT

The prevalence of mitral regurgitation (MR), particularly degenerative MR (DMR), rises with advancing age. Elderly patients frequently carry increased surgical risk due to frailty and comorbidities, leading to a prohibitive risk of conventional surgery. For such patients, mitral transcatheter edge-to-edge repair (M-TEER) provides a minimally invasive alternative to surgical repair. Data from large registries, including TRAMI (Transcatheter Mitral Valve Interventions) and EXPAND (The MitraClip™ EXPAND Study of the Next Generation of MitraClip™ Devices), demonstrate high procedural success, low 30-day mortality (2–3%) and stroke rates (<1%), and durable improvements in functional status and quality of life (QoL) in elderly cohorts. Although definitions of “elderly” vary between studies (≥75, ≥80, or ≥85 years) and benefits are consistently observed, elderly was defined  ≥75 years within this review. For selected patients unsuitable for M-TEER, transcatheter mitral valve replacement (TMVR) can achieve effective MR elimination, with reported 1-year mortality ranging from 7% to 17% in early transfemoral, transseptal experiences and up to 29% after transapical TMVR. This review summarizes current evidence on safety, functional outcomes, QoL, survival, emerging replacement strategies, and conservative management in elderly patients with MR.

Plain Language Summary

Mitral regurgitation (MR) becomes more common with increasing age, especially the degenerative type caused by age-related valve changes. Older patients often have additional health conditions and frailty, which increase the risk for heart surgery. Mitral transcatheter edge-to-edge repair (M-TEER) offers an alternative using access through a blood vessel. Large registries show that M-TEER is successful in more than 90% of cases, with low complication rates, about 2–3% risk of death and 1% or less risk of stroke within 30 days in elderly patients. Beneficial outcomes, especially heart failure symptoms and quality of life, improve in these patients following this procedure. Different studies define “elderly” in slightly different ways, from 75 to 85 years and older, but positive results are seen in all these age groups. Within this review, patients 75 years and older were defined as elderly. In patients with unsuitable anatomy for M-TEER, transcatheter mitral valve replacement might be another option, which can eliminate MR but carries a higher risk of death. This review summarizes the research on safety, physical function, quality of life, medication-based treatment, and survival for older adults receiving transcatheter mitral valve repair.

GRAPHICAL ABSTRACT

1. Introduction

The prevalence of mitral regurgitation (MR) increases with age and is reported to be about 7% for moderate-to-severe MR in nonagenerians compared with <2% in those under 60 years [1,2]. Simultaneously, MR is associated with excess mortality, heart failure hospitalization and impaired quality of life (QOL) [3,4]. The current ESC guideline for the management of valvular heart disease recommends transcatheter mitral valve edge-to-edge repair (M-TEER) in patients with ventricular functional MR (vFMR), irrespective of age [5]. Degenerative MR (DMR) is the leading MR subtype in the elderly and should be surgically repaired, if feasible, but age, comorbidities, and frailty translate into elevated perioperative risk as typically assessed by EuroSCORE II (The European System for Cardiac Operative Risk Evaluation) and the STS score (The Society of Thoracic Surgeons) [6]. Patients with elevated surgical risk, commonly reflected by EuroSCORE II values ≥8% or comparable STS-predicted risk estimates are at substantially increased risk of perioperative mortality and morbidity [5]. Minimally invasive mitral valve surgery may offer reduced surgical trauma in selected candidates but still requires general anesthesia and heart lung machine [7]. Contrarily, transcatheter approaches display a less invasive treatment option by avoiding cardiopulmonary bypass and the burden of surgical repair or replacement. Therefore, when surgical risk is high, minimally invasive surgery is not appropriate, or the expected benefit of surgery is outweighed by frailty and comorbidities, transcatheter repair or replacement should be considered [5]. Especially elderly patients with high frailty burden and/or relevant comorbidities transcatheter are ideal candidates for transcatheter approaches [8,9].

The definition of “elderly” varies across different studies reporting on transcatheter mitral valve interventions from ≥75, ≥80, to ≥85 years. Considering published analyses stratifying by age, ≥75 years appears to be pragmatic definition of elderly patients for the purpose of this review. Nevertheless, standardized age strata, e.g., 75–79, 80–84, ≥85, and ≥90 years might offer additional age-related information.

M-TEER has become the most widely performed intervention in high-risk elderly patients with DMR. Advances in device technology, including newer-generation systems (e.g., MitraClip™ G4, PASCAL), offer greater procedural precision, enhanced leaflet grasping, and tailored device sizing for complex anatomies [10]. These improvements, combined with the minimally invasive nature of M-TEER, have translated into favorable short- and long-term outcomes across a spectrum of elderly populations [4,11–13]. Concurrently, several platforms for transcatheter mitral valve replacement (TMVR) have developed in the recent years and offer effective MR grade reduction for different mitral valve anatomies [14–17]. This review summarizes current evidence on transcatheter mitral valve interventions in elderly patients, focusing on procedural safety, symptom relief, QOL, survival, and emerging replacement strategies.

2. Treatment approaches and outcomes in elderly patients with mitral regurgitation

2.1. Safety

Evidence consistently shows that M-TEER maintains high safety across advanced age groups. A recent analysis of EXPANDed (The MitraClip® EXPAND Study of the Next Generation of MitraClip® Devices) including pooled patient data from the EXPAND [18] and EXPAND G4 [19] studies of real-world data reported no difference regarding 30-day outcomes for DMR patients ≥85 compared with <85 years [11]. Specifically, 30-day mortality did not differ (3.1 vs. 1.4%, p = 0.15) [11]. Similar results were reported for 790 nonagenarians, that were propensity score matched with patients <90 years using the Nationwide Inpatient Sample (NIS) database (in-hospital mortality: 0.7 vs. 2.0%, p = 0.29) [20]. A specific analysis of octo- and nonagenarians was performed by Christidi et al. and observed a numerical increase of 30-day mortality: <80 years (1.8%), 80–90 years (2.7%) and 90+ years (4.0%), however, without statistical significance (p = 0.66) [21]. Even lower in-hospital mortality of 0.2% was reported for 513 patients ≥80 years from a single center analysis including >1,000 patients [13]. The German TRAMI (Transcatheter Mitral Valve Interventions) registry observed comparable in-hospital mortality in 525 patients ≥76 years to younger patients <76 years (2.9 vs. 2.8%, p = 0.96) [12]. An even larger analysis of the National Readmissions Database reported in-hospital mortality of >8,000 octo- and >1,500 nonagenarians (2.1 and 2.7%), which did not differ significantly from almost 9,000 patients <80 years (2.6%) [22]. Acute stroke displays another potential complication of the procedure but was reported in <1% of the elderly patients across different studies [11,12,20]. From a clinical perspective, these findings suggest that chronological age alone should not be considered a contraindication for M-TEER. The reported low rates of periprocedural mortality and stroke across different studies indicate that procedural risk is often acceptable even in octo- and nonagenarians, when considered eligible for this procedure. Consequently, decision-making should focus less on age thresholds and more on individual selection criteria [23].

2.2. Functional outcomes

According to current evidence, M-TEER consistently improved functional status in elderly patients. Procedural success was high (95%) and did not differ between patients ≥76 and <76 in a sub-analysis of the German TRAMI registry [12]. This is also reflected by comparable postprocedural symptoms (New York Heart Association [NYHA] IV: 13 vs. 9%; p = 0.020) [12]. In the recently presented EXPANDed analysis, most elderly patients were in NYHA class I or II at 1 year, with comparable rates in patients ≥85 and <85 years (81 vs. 86% (p = 0.22) [11]. These data suggest that elderly patients not only tolerate M-TEER but frequently experience a clinically meaningful shift from symptomatic limitation toward lower NYHA classes. These findings support a clinically meaningful improvement in functional status among elderly patients. This is also in line with the technical result of 1-year MR severity (MR ≤1+: 81 vs. 88%, p = 0.08), which shows a slight trend toward higher MR grades at 1-year follow-up, however, both rates are acceptable considering consistent NYHA improvement regardless of age [11]. While these studies included both DMR and FMR, a COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) sub-analysis of elderly patients – defined as ≥74 years – with FMR only demonstrated beneficial effects on 2-year heart failure hospitalization (Hazard ratio [HR]: 0.67, 95%-Confidence interval (CI): 0.48–0.93) [4], however, an even larger benefit was observed for younger patients <74 years (HR: 0.37, 95%-CI 0.25–0.55, p_interaction = 0.03) [4]. Overall, available data suggest that advanced age does not substantially impair procedural success or NYHA class improvement after M-TEER in selected patients. Especially in elderly patients, symptom relief is often the primary treatment goal, particularly when competing non-cardiac diseases limit long-term survival.

2.3. Quality of life

Although elderly patients are associated with an increased comorbidity burden, QOL improvement is still observed in these patients. To better define the extent of improvement, consideration of patient-reported outcome measures alongside NYHA class is important. EXPANDed did not observe a difference in KCCQ (Kansas City Cardiomyopathy Questionnaire) scores at 1-year comparing patients with DMR ≥85 and <85 years (62.2 vs. 65.3%, p = 0.47) [11,21]. Likewise, elderly FMR patients from the randomized COAPT experienced consistent KCCQ-Score improvements at 2 years compared with younger patients (17.8 ± 27.1 vs. 17.0 ± 24.3, p_interaction = 0.71) [4]. Accordingly, better QOL assessed by the Minnesota Living with Heart Failure Questionnaire was observed für septua-, octa-, and nonagenerians by Christidi et al. [21]. These findings indicate that patient-reported benefit after M-TEER can be expected in selected elderly patients within the range of age categories and MR etiology. In the context of advanced age, QOL improvement may be as relevant as survival prolongation. This strengthens the importance of patient reported outcomes into preprocedural assessment and Heart-Team evaluation, especially when the expected benefit is improvement in daily activities, independence, and reduction of heart-failure symptoms rather than isolated treatment of MR. These findings support M-TEER in the elderly when treatment goals include symptomatic and functional improvement.

2.4. Mortality

Mortality assessment in elderly cohorts is inherently influenced by baseline risk, but comparative analyses show reassuring outcomes. Regarding 1-year mortality, several studies reported acceptable outcomes in elderly patients undergoing M-TEER. Analysis of an all-comer cohort with >1,000 patients reported comparable 1-year all-cause mortality rates for elderly patients ≥80 compared to <80 years (18.0 vs. 16.4%, p = 0.577) [13]. EXPANDed demonstrated only slightly higher 1-year mortality in DMR patients ≥85 years (12.2 vs. 9.9%; HR: 1.74 [95%-CI 1.02–2.98], p = 0.004) [11]. Longer-term data suggest a more pronounced effect of age on survival. Regarding 2-year mortality, elevated mortality was observed for nona- (28.0%) and octogenarians (32.4%) compared to septuagenarians (19.8%; p = 0.008) by Christidi et al. [21]. COAPT’s FMR patients also showed elevated 2-year mortality rates (35.7 vs. 20.0%) for patients ≥74 years [4]. 3-year mortality rates are reported to be even higher in the elderly ≥80 years from an all-comer registry (43.1% vs. 33%, p = 0.035) [13]. Independent predictors of adverse survival include elevated NT-proBNP, higher baseline MR grade, and elevated EuroSCORE II [13]. These longer-term results demonstrate that excess mortality becomes more apparent with advanced follow-up in elderly patients and is influenced by progressive heart failure and comorbidities, rather than age alone. These findings indicate that M-TEER may mitigate age-related mortality for at least 2 years in patients with symptomatic MR, confirming the benefit of M-TEER in the elderly. This is consistent with the ESC guideline, which recommends M-TEER in patients with a life expectancy greater than 12 months, emphasizing that advanced age alone should not preclude treatment [23]. In clinical practice, treatment strategy should predominantly aim at a relevant benefit within the patient’s expected lifespan, rather than the achievement of the same long-term survival as younger patients.

2.5. Transcatheter mitral valve replacement

Despite advances of the M-TEER procedure, specific anatomies, including a small mitral valve area or severe calcification, remain unsuitable for transcatheter edge-to-edge repair. Especially for elderly patients with a prohibitive risk for surgery, transfemoral TMVR platforms have emerged as an alternative with promising outcomes: The Intrepid TMVR study included elderly patients with a median age of 80 [Interquartile range 75–85] years and 90% degenerative MR [16]. Sustained MR elimination and 1-year mortality of 6.7% were observed [16]. Early results from the HighLife system also demonstrated sustained MR elimination in a cohort with a mean age of 76 years and 90% functional MR; 1-year mortality was 16.7% [15,16]. Furthermore, the AltaValve system demonstrated effective MR reduction in patients with MAC [24] and the Edwards Sapien M3 has shown safety and effective reduction in patients with DMR, FMR, and mixed MR etiology [14]. In these early TMVR experiences, effective MR elimination was accompanied by symptomatic and patient-reported improvement, although mortality varied substantially according to device platform, access route, and baseline risk.

Regarding transapical mitral valve replacement using the Tendyne™ system, effective MR and NYHA class reduction were demonstrated by the TENDER (Tendyne™ European Experience) registry; however, 1-year mortality was 28.6% [17]. Additionally, the recent SUMMIT-MAC study incorporating 103 patients with severe MAC and MR or mitral stenosis undergoing TMVR using the Tendyne™ system confirmed successful MR treatment in an elderly cohort with a mean age of 78.0 ± 6.5 years [25]. Notably, a recently presented propensity score matched comparison of transapical TMVR vs. transfemoral TMVR observed an increased postprocedural bleeding rate and indicated a numerically lower 1-year mortality using the transfemoral TMVR, suggesting that the transfemoral, transseptal approach might offer beneficial outcomes in selected patients [26].

Available data suggest that transfemoral, transseptal TMVR platforms may be especially suitable in elderly patients by avoiding high bleeding risk and procedural burden associated with thoracotomy or apical access. Nevertheless, based on current data, TMVR in elderly patients should be perceived complementary rather than competitive to M-TEER as presented in Table 1 and the graphical abstract. At present, TMVR is most relevant for patients with severe MR who are ineligible for surgery and have an anatomy unsuitable for edge-to-edge repair including severe leaflet calcification, restricted leaflet motion, large coaptation gaps, or mitral annular calcification. However, the higher bleeding risk and mortality observed within transapical platforms highlight the need for careful patient selection. The increasing availability of MR treatment options emphasizes that beyond consideration of MR etiology, such as atrial, annular, and ventricular geometry, assessment of frailty, right ventricular function, expected survival, quality of life goals, access site, and bleeding risk is required. However, longer-term data are still required to clarify long-term durability and optimal patient selection for TMVR [27].

Table 1.

Comparison of interventional treatment strategies for elderly patients with mitral regurgitation.

	M-TEER	TMVR
Current role	Established option for high-risk or inoperable patients with suitable anatomy	Emerging option for patients unsuitable for M-TEER or surgery
Typical setting	Symptomatic severe DMR or FMR, high surgical risk, and feasible leaflet approximation	Severe MR and anatomy unsuitable for M-TEER, e.g., severe calcification, large coaptation gap, restricted leaflet motion, mitral valve stenosis or MAC
Suitable anatomy	Adequate leaflet tissue, suitable coaptation length, acceptable transmitral gradient/opening area, no prohibitive calcification	Adequate atrial/annular/ventricular anatomy, acceptable risk of LVOT obstruction, system-specific sizing criteria
Access-site	Minimally invasive, usually transfemoral/transseptal	System-dependent; transfemoral/transseptal or transapical
Procedural risk in elderly patients	Generally low peri-procedural mortality and stroke rates in selected elderly cohorts	Higher and more variable risk; Association of transapical systems with bleeding and higher mortality
Main limitations	Potential residual/recurrent MR; not suitable for severe calcification, small valve area, or unfavorable leaflet anatomy	Limited long-term data, risk of LVOT obstruction, higher procedural complexity; Access related risks
When to consider	Preferred when anatomy is suitable and expected symptomatic benefit is meaningful	Consider when M-TEER is anatomically unsuitable and procedural risk is acceptable

Abbreviations: DMR: degenerative mitral regurgitation; FMR: functional mitral regurgitation; LVOT: Left ventricular outflow tract; MAC: mitral annulus calcification; MR: mitral regurgitation; M-TEER: mitral valve edge-to-edge repair; TMVR: transcatheter mitral valve replacement.

2.6. Conservative management and when not to intervene

Even though mitral valve intervention options have increased over the last years, conservative treatment remains appropriate in selected and especially elderly patients. Specifically, in elderly FMR patients, the effect of M-TEER was more pronounced in the younger compared to the elderly regarding the reduction of heart failure hospitalization according to a COAPT sub-analysis [4]. This further underlines the high importance of optimized guideline-directed therapy of heart failure in elderly patients, which includes pharmacological and device therapy before intervention of functional MR in accordance with guideline recommendations [5]. Consequently, especially in elderly patients with FMR, mitral valve intervention should be reserved for those with persistent severe MR and relevant symptoms despite adequate treatment.

In elderly DMR patients not eligible for surgery or transcatheter intervention, conservative treatment mainly focuses on symptom control, management of congestion, and optimized treatment of comorbidities like atrial fibrillation, hypertension, and renal disease. Specifically, when symptoms are mild and MR is not the main cause of functional limitation, conservative treatment should be the preferred treatment approach at first.

Taken together, conservative treatment of MR should be preferred in very high frailty, advanced non-cardiac diseases, limited life expectancy, and may better harmonize with patient goals than invasive treatment in selected patients.

2.7. Cost effectiveness

Consideration of cost-effectiveness when treating elderly patients with high-cost interventions is important in the context of raising healthcare costs and its associated social implications [27]. This consideration mainly compares the costs of interventional treatment with an increased rate of heart failure hospitalization and integrates the intervention’s impact on quality-of-life improvement by reducing symptoms and MR-related hospitalization. For functional MR, the COAPT economic analysis demonstrated a cost-effectiveness ratio of $40 361 per life-year and $55 600 per quality-adjusted life-year gained, which was deemed acceptable compared to corresponding cost-thresholds in the United States [28]. Analyses from European sites and Canada demonstrate that procedure costs vary between countries but are consistently below country-specific willingness-to-pay thresholds for quality-of-life years [29]. However, increased experience, expertise, and new-generation TEER systems offer safer and more efficient procedures leading to shorter procedural time, fewer complications, and device numbers, which themselves are associated with higher procedure costs [30]. This continuous improvement could lead to reduced procedure‑related costs in the future and thereby may offer this intervention to a significantly larger group of patients. Nevertheless, these data underline that especially in elderly patients with competing non-cardiac mortality risks, careful patient selection and a life expectancy greater than 12 months are crucial to actually gain quality-adjusted life-years by M-TEER. Future analyses should reassess the additional costs of this intervention compared to conservative treatment in the setting of advanced systems, expertise, and streamlined processes.

3. Conclusion

For elderly patients with vFMR and DMR with high surgical risk, M-TEER represents the therapy of choice, combining excellent procedural safety with meaningful improvements in functional status and QoL. Mortality remains elevated due to age and comorbidities, but registry and trial evidence suggest that M-TEER mitigates age-related risk and delivers clinically relevant benefit. TMVR provides an alternative in anatomically unsuitable patients, though current devices are associated with higher mortality. Heart Team assessment remains essential to tailor therapy, ensuring that advanced age alone does not deny patients access to effective intervention.

3.1. Future perspectives

Over the next 5–10 years, increasing treatment options for mitral valve repair will demand more individualized patient assessment including anatomical features, access site, and procedure-specific risk, but also geriatric measures like frailty, independence, and quality of life. Probably, M-TEER will remain the preferred transcatheter therapy in patients with suitable anatomy and further expand to more complex anatomies due to advanced systems and procedure expertise. Simultaneously, TMVR will evolve to a more complementary strategy for patients with unsuitable anatomy for M-TEER. Particularly in elderly patients, transfemoral, transseptal TMVR displays an important treatment option by less invasiveness compared to thoracotomy and apical access. Finally, mitral valve treatment will distance from age-based treatment decisions and move toward individualized, feature-based strategies that identify elderly patients most likely to achieve meaningful symptomatic and functional benefit while avoiding overtreatment. Future studies should focus on optimal patient-selection for TMVR versus M-TEER, standardized frailty assessment, and integration of geriatric outcomes.

Funding Statement

The paper was not funded.

Article highlights

• Mitral regurgitation is prevalent in elderly patients and is associated with heart failure hospitalization, impaired quality of life, and increased mortality.

• Chronological age alone should not determine treatment eligibility. Heart Team decision-making should integrate biological age, frailty, comorbidity burden, anatomical feasibility, life expectancy, patient preferences, and quality of life.

• M-TEER is currently the preferred transcatheter treatment option for elderly patients with severe MR, high or prohibitive surgical risk, and suitable valve anatomy.

• Contemporary registry and trial data show that M-TEER can be performed safely in selected elderly patients, including octo- and nonagenarians, with low short-term mortality and stroke rates and functional improvement.

• TMVR is an emerging complementary option for selected high-risk or inoperable patients with anatomy unsuitable for durable M-TEER. Transfemoral, transseptal approaches may be particularly relevant for elderly patients by its acceptable safety profile.

Disclosure statement

Prof. Keßler and Prof. Rottbauer have received speaker honoraria Edwards Lifesciences and Abbott Laboratories. Prof. Rottbauer is a proctor for HighLife. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.