Clinical outcomes of conventional surgery versus MitraClip® therapy for moderate to severe symptomatic mitral valve regurgitation in the elderly population: an institutional experience

More than 9% of patients ≥75 years have significant MR [1]. The proportion of individuals aged ≥75 with symptomatic MR is estimated to become a growing clinical problem. The decision whether to refer an elderly patient with symptomatic MR for mitral valve surgery and appropriate timing of referral is a highly debated issue. Age, severe MR and reduced left ventricular function amongst others have been identified as independent patient factors associated with non referal for mitral valve surgery [2]. Though, due to outstanding improvements in diagnostic modalities, patient selection criteria and operative techniques over the years, the operative mortality, in-hospital morbidity and long term outcomes associated with mitral valve surgery has significantly improved [3]. However, the benefit of surgery in the very elder population despite these significant improvements over the years has not been clearly documented. Increasing life expectancy and associated increase in the prevalence of valvular heart diseases, especially MR amongst the very elderly population is expected to become a rising clinical problem in the industrialized nations. Many patients at this advanced age will likely present with concomitant cardiac pathologies, necessitating surgical attention [4, 5]. The novel MitraClip device is anticipated to play a crucial role in addressing MR in this elderly patient population. In this context, staged percutaneous management of concomitant pathologies may be feasible in some cases. Coronary heart disease, aortic valve stenosis and certain pathologic rhythms may be treated in a staged total percutaneous manner. Data on the fate of moderate tricuspid regurgitation left untreated during conventional surgery remain insufficient and this is equally the case with percutaneous mitral valve repair. The impact of these residual pathologies on short and long term outcome has not been fully evaluated, leaving complete surgical intervention as gold standard [6]. Though there are indications that the novel MitraClip device may confer superior acute outcomes, with lower procedural mortality in symptomatic patients, however, long term outcomes, especially in the very elderly is not well known. The impact of residual MR, atrial septal defect, atrial fibrillation, incomplete revascularization and tricuspid valve disease in this patient population treated with the MitraClip device is not known. Despite higher mortality and morbidity in the acute phase post surgery, surgery in most cases offer complete repair of concomitant cardiac pathologies [7–10]. We sought to compare the overall outcome of conventional mitral valve surgery vs MitraClip treatment in a single center cohort of 84 patients.

This study is based on our experience with very elderly patients with symptomatic moderate- severe MR, who underwent correction of this valve pathology during the period between October 2008 and October 2014.

Patients underwent surgical correction of MR with either mitral valve repair, replacement or placement of ≥1 MitraClip devices. A retrospective assessment was then perfomed after all follow-up data were retrieved. This was accomplished by obtaining all medical records from nursing home personnel, family physician or patient/family members. Follow- up was obtained at different intervals post index procedure (last survey or death) in all 84 patients included in this study.

Mitral valve surgery in the elderly oftentimes multi morbid population is a highly debated issue. Although more elderly patients with MR are increasingly being identified and referred for surgery, still as much as 50% are often denied surgery due to perceived higher risk and lower benefit expectation from surgical correction of MR [2]. This tendency is partly justifiable for secondary MR due to the fact that results of surgery are unpredictable in improving patient outcomes. Moreover surgery for secondary MR has never been compared with guidelines directed medical therapy (GDMT) alone for left ventricular dysfunction in a prospective randomized manner. Studies comparing outcomes of patients with secondary MR treated with mitral valve repair and those treated with GDMT are mostly retrospective in nature, using propensity score matching and have failed to demonstrate an advantage of surgery in improving survival [13]. However, results of surgical elimination of MR in primary (degenerative) MR on the other hand, especially reconstructive surgery are excellent.

Some studies provided insight into potential poorer prognosis for patients with functional MR and left ventricular dysfunction and this is especially true for patients with recent acute myocardial infarction and for patients with chronic ischemic and non ischemic cardiomyopathy [14]. It was shown that even with the current GDMT, there was always a tendency to adverse prognosis due to untreated ischemic functional MR. Therefore this category of patients who remain symptomatic despite GDMT and CRT may be a reasonable target for surgical or interventional therapy of functional MR. Swaans et al. recently reported mortality rates in patients receiving neither surgery nor percutaneous therapy for MR that even exceeded that of either surgical or interventional therapy [15]. This report provided new insights into the potential survival benefits of mitral valve intervention (both surgical and interventional) compared with GDMT alone in patients with LV dysfunction and secondary MR [15]. In the Survival and Ventricular Enlargement Trial (SAVE) patients with even mild functional MR after myocardial infarction were more likely to experience cardiovascular mortality (29% vs. 12%; p < 0.001), and severe heart failure (24% vs. 16%; p < 0.0153) than those without MR [16]. Trichon et al. reported 2057 patients with ischemic MR and chronic LV systolic dysfunction and showed residual MR to be an independent predictor of mortality. They also found significantly lower survival rates at 1, 3 and 5 years of heart failure patients with moderate to severe MR versus those without MR or with mild MR [17]. Hence, none referral of elderly symptomatic patients with MR for at least surgical evaluation, due to age alone is highly debatable. The optimal timing for surgery or percutaneous intervention is also critical in reducing mortality rates associated with both surgery and interventional therapy. The percutaneous edge-to-edge device has since its first application in human, continuously improved, and currently demonstrates superb acute interventional outcomes in the elderly population with MR classified as high surgical risk [18, 19]. Though operative risks of mitral valve surgery reduced significantly during the last decades [20], however quality of life after such surgical interventions, a factor of great importance in the elderly population has rarely been reported. Maissano et al [21] found that quality of life was suboptimal in more than half of elderly patients following mitral valve surgery and that surgical technique did not impact quality of life at follow up. They identified several factors significantly related to increased Minnesota Living With Heart Failure (MLHF) - score at follow-up after valve surgery in the elderly. Age, preoperative atrial fibrillation (or rhythm other than sinus rhythm at follow up), EuroSCORE, Charlson score and recurrent/residual MR at follow up amongst others were significantly associated with poorer quality of life at follow up. They suggested that quality of life should be a better indicator of successful surgery/intervention in this age group than survival alone. In our study, though the 30-day mortality was slightly higher in the surgical cohort, but there was equalization of mortality rates as time progressed, with even higher mortality rate in the MitraClip group (depicted in Fig. 1). At 1- year- follow up surgical patients had lower MR recurrence than found in the Mitraclip group. Kaneko et al in their recent study found that residual MR 2+ was associated with poorer prognosis in patients with impaired LV function, renal dysfunction, and severe heart failure. They suggested that the optimal endpoint of MC procedure should be individualized according to each patient's baseline characteristic [22].

The impact of tricuspid regurgitation left untreated at time of Mitraclip intervention was recently reported by ohno et al [23] who found that estimates for freedom from combined endpoint of death and rehospitalisation for heart failure were worse in moderate/severe tricuspid regurgitation group of patients treated with the MitraClip device compared with those with none/mild tricuspid regurgitation (67.7% vs 88.8% log-rank p = 0.015). Overall NYHA was also found to be worse in this group of patients with moderate/severe tricuspid regurgitation, despite improved LVEF and ventricular volumes at 12 month-follow-up. Since the current practice of Mitraclip intervention does not include concomitant cardiac interventions in the aortic valve, tricuspid valve, atrial fibrillation ablation or complete myocardial revascularisation, all of which have high prevalence in the elderly population, adequate patient selection should identify patients who would rather benefit from complete surgical intervention despite age.

Mitral valve surgical procedures in the very elderly with symptomatic MR is associated with profound operative morbidity and mortality rates, especially in deem of frequently associated comorbidities [10]. Mirabel et al [2] from the Euro Heart Survey on heart valve diseases reported that in a group of 396 patients with symptomatic MR, surgery was denied in 49%, with age, impaired LVEF and several comorbidities playing the main role in the decision not to offer surgery. However untreated symptomatic secondary MR seems to confer even higher mortality and morbidity. MitraClip therapy, though has acceptable procedural outcomes, but long term results are pending and the durability of acute reduction of MR in certain patients remains controversial. De Bonis et al. recently failed to confirm the results of EVEREST II trial in which it was observed that the MItraClip results remained stable in the long term if initial therapy was successfull. Infact they found that patients with FMR, despite optimal initial results of MitraClip intervention had the tendency to develop recurrent MR. Whether FMR at this time can be seen as risk factor for recurrent MR after MitraClip therapy remain to be confirmed in a prospective randomized trial.

Treatment of concomitant cardiac pathologies, which have increased prevalence in this age group, is very limited. The impact of untreated concomitant cardiac pathologies, left untreated at the time of MitraClip therapy versus complete surgical interventions on the mid and long term outcomes should be the subject of future studies. Our acute procedural outcomes in the mitral surgical group is in line with published data on mortality and morbidity rates after mitral valve surgery in the very elderly, despite several concomitant surgical procedures and high EuroScore II values, and mid term outcomes are impressive.

As the number of elderly patients with mitral valve disease is expected to increase rapidly, there is need for data providing evidence on the benefits and harm of both conventional MV surgery and several percutaneous therapeutic options, being propagated for MR treatment in these high risk patients. As percutaneous mitral valve repair options are rapidly gaining ground as alternative option for mitral valve repair in these high risk surgical patients, at the same time some patients are reoperated successfully after failed interventions. However this is expected to decrease with perfection of this technology. Adequate patient selection prior to decision for either conventional surgery or MitraClip therapy should be pursued in the future. Age alone should at present not be a criterium for pro MitraClip therapy, rather comorbidities predisposing to high prohibitive risk of surgery and in those cases with ambiguous survival benefit of surgery. Benefit of surgery for MR due to ischemic cardiomyopathy remains a highly debated issue [24–26]. Multidisciplinary team approach is key to providing optimal individually tailored treatment for elderly patients with symptomatic MR. Primary and secondary MR are very different entities in terms of etiology, management and prognosis and these differences should be put into account during multidisciplinary decision pro or contra surgery or interventional treatment of symptomatic MR.

This is a retrospective, single-center observational study with a very limited number of observed patients. There may be some, unidentified confounding factors that might have influenced certain results, so strong conclusions from our study should not yet be deduced or generalized, until our results is confirmed by prospective and randomized clinical trials. Follow-up data were obtained by both facsimile questionnaire and telephone interviews with patients family practitioner and cardiologist. Hence, accuracy of grading NYHA functional class, MR grades may have been compromised by interobserver bias. Patient selection for the respective procedures did not follow standard operating procedures, but rather decisions were made after interdisciplinary consultation in each case within a heart team. The completely different burden of both treatment arms, with patients in the surgical arm receiving different and at times multiple concomitant procedures with subsequent impact on early clinical outcome is another important limitation.

In terms of quality of life, unfortunately due to the retrospective nature of our study, quality of life was not assessed preoperatively and therefore assessing quality of life during follow-up would not provide data usefull for any reasonable comparison.

Another important limitation is that the number of patients whose data were available for 1-year followed-up was less in the mitraClip group.

Elderly patients presenting with moderate to severe symptomatic MR may either be treated by conventional surgery or with the MitraClip device with acceptable acute outcomes. The decision for treatment with the MitraClip device should not depend on age alone rather on cumulative risk of conventional surgery. Concomitant cardiac pathologies, often times treated simultaneously during surgery for symptomatic MR may be omitted, if patients are scheduled outright to MitraClip treatment. The effect of concomitant cardiac pathologies left untreated at the time of interventional mitral valve repair on outcome after MitraClip therapy remain widely unknown.