Combined Minimally Invasive Mitral Valve Surgery and Percutaneous Coronary Intervention: A Hybrid Concept for Patients with Mitral Valve and Coronary Pathologies

We evaluated the feasibility of hybrid percutaneous coronary intervention (PCI) and minimally invasive mitral valve surgery (MIMVS) in patients with concomitant coronary and mitral disease. Of 534 patients who underwent MIMVS at our institution between 2012 and 2018, those with combined mitral and single vessel coronary pathologies who underwent MIMVS and PCI were included. Patients were excluded if they had endocarditis or required emergency procedures. Preprocedural, procedural, and postprocedural data were retrospectively analyzed. In total, 10 patients (median age, 75 years; 7 males) with a median ejection fraction (EF) of 60% were included. Nine patients underwent PCI before and one after MIMVS. The success rate was 100% in both procedures. There were no postoperative myocardial infarctions or strokes. Two patients developed delirium and one required re-thoracotomy for bleeding. The median stay in intensive care and the hospital was 3 and 8 days, respectively. The 30-day survival rate was 100%. A hybrid PCI and MIMVS approach is feasible in patients with mitral valve and single vessel coronary disease. In combined pathologies, the revascularization strategy should be evaluated independent from the mitral valve pathology in the presence of MIMVS expertise. Extension of this recommendation to multivessel disease should be evaluated in future studies.


Introduction
There is an increasing demand for minimally invasive mitral valve surgery (MIMVS) because of the cosmetic benefits, shorter hospital stay, and avoidance of sternotomy and its wound complications, making it a more desirable option than sternotomy.The aim of MIMVS is to treat patients with mitral valve pathologies using a favorable surgical approach [1,2].However, the presence of a concomitant coronary pathology might influence the treatment strategy for both the coronary pathology and the mitral valve disease.According to the European Society of Cardiology (ESC) and the European Association of Cardiothoracic Surgery (EACTS) guidelines for myocardial revascularization, the choice of revascularization strategy (percutaneous coronary intervention [PCI] vs. coronary artery bypass grafting [CABG]) might be influenced by the presence of any indications of further cardiac procedures, such as valve surgery [3].Based on these recommendations, patients with concomitant mitral valve and coronary pathologies-who are candidates for concomitant surgical revascularization according to the latest ESC/EACTS guidelines-are usually operated on via the median sternotomy to allow sufficient exposure of the coronary arteries [3].
The guidelines do not differentiate between single, double, or triple vessel disease in cases of concomitant valve surgery or between minimally invasive or classic approaches for valve therapy.Single vessel disease, which can be treated sufficiently endovascularly, is recommended to be treated surgically if concomitant valve surgery is to be performed [3].Yet, this decision might be the leading indication for changing the surgical approach and denying the patient a minimally invasive procedure.The feasibility of MIMVS and PCI as a hybrid concept for patients with mitral valve and coronary pathologies is yet to be investigated.The aim of this study was to present our institution's initial experience with this hybrid concept in patients with combined pathologies.

Patient Cohort
Between January 2012 and April 2018, 534 patients who underwent isolated or combined MIMVS at our institution were screened for inclusion in this retrospective descriptive study.Patients were included if they had a combined mitral pathology and an indication for single vessel coronary revascularization and underwent hybrid therapy with MIMVS and interventional therapy for coronary disease.Patients who underwent a non-planned PCI or emergency procedures and those with endocarditis were excluded from the study.The study was approved by the institutional review board.

Data Collection
All data were collected from the patient records.The pre-management patient data, decision of the heart team, PCI, and operative procedural details as well as post-management results were retrospectively collected and analyzed.

Statistical Analysis and Reporting
Continuous variables are presented as medians with interquartile ranges (IQRs).Categorical variables are presented as absolute numbers.All statistical tests were performed using SPSS v22.0 (IBM Inc., Armonk, NY, USA).

Results
Overall, 10 patients who met the inclusion criteria were included in the analysis.

Demographic and Medical Data
Tables 1 and 2 summarizes the patient demographic and medical data.The overall median age was 75 years and seven patients were males.The median body mass index was 29.4 (23.7-31.6)kg/m 2 .The comorbidities included hyperlipidemia (n = 7), renal insufficiency (n = 4), and diabetes mellitus (n = 3).The median creatinine value in the patient cohort was 1.08 mg/dl (0.84-1.87).None of the patients were on dialysis or had chronic obstructive pulmonary disease (COPD), liver failure, or peripheral vascular disease.
The analysis of the cardiac data revealed a median left ventricular ejection fraction (EF) of 60% (40-60%).Three patients had atrial fibrillation.All patients were of New York Heart Association (NYHA) class 3. Two patients were of Canadian Cardiac Society (CCS) class 2. All patients had mitral valve insufficiency with no stenosis and one patient had tricuspid regurgitation.None of the patients had aortic valve or aortic diseases.There were no cases of acute myocardial infarctions.Four patients had a past history of myocardial infarction; one patient each had it within 1 month and 90 days before the procedure, while two patients had it more than 90 days before the procedure.Two patients had a history of CABG in 1993 and 2003, respectively, both of whom underwent totally arterial bypass grafting to the left coronary system with no bypass grafting to the then non-diseased right coronary system that required intervention in the present study.Coronary angiography confirmed patent bypass grafts.None of the patients had a previous mitral valve surgery.The details of coronary findings are summarized in Table 1 and those of the mitral valve pathology are summarized in Table 2.

Coronary Intervention
Nine patients underwent PCI with stent implantation before the surgery.The median time between PCI and MIMVS was 48 (IQR, 8-63) days.One patient who had previously undergone cardiac surgery underwent the current coronary intervention 48 days after the procedure.Overall, the procedural success rate was 100%.The stents used included Coroflex, Coroflex Blue, Coroflex Blue Ultra, Coroflex ISAR (B.Braun Melsungen AG, Melsungen, Germany), and Xience pro (Abbott Vascular, Santa Clara, CA, USA).There were no periprocedural complications.All patients received dual antiplatelet therapy with acetylsalicylic acid and clopidogrel.Table 3 summarizes the details of the coronary interventions performed.

Surgical Procedure
MIMVS was performed as previously described [4].In brief, the patient was brought to the operation theatre, placed under general anesthesia, and intubated with a singlelumen endotracheal tube.The patient was then put on cardiopulmonary bypass (CPB) via femoral arterial and venous cannulae.In case of concomitant tricuspid valve surgery, a second venous cannula was inserted into the right jugular vein.After dissecting pleural adhesions, if present, via an anterolateral minithoracotomy, the CPB was initiated and the heart and aorta were exposed.In eight patients, the aorta was cross-clamped with a Valve Gate™ transthoracic aortic clamp (Geister, Tuttlingen, Germany) and antegrade Bretschneider's Custodiol ® crystalloid cardioplegia (Dr.Franz Köhler Chemie, Bensheim, Germany) was administered via the aortic root, followed by left atriotomy and exposure of the mitral valve with a Valve Gate™ special minimally invasive atrial retractor (Geister, Tuttlingen, Germany).In one patient with extensive intrapericardial adhesions and in one of two patients who had previously undergone coronary surgery, cross-clamping of the aorta was not possible due to excessive adhesions; therefore, atriotomy and mitral valve exposure were performed in a beating heart.In these two patients, the heart was put into ventricular fibrillation directly before introducing the mitral ring into the left atrium to prevent an air embolism after achieving a competent valve.After completion of the mitral valve repair, the left atrium was closed and the aortic clamp was removed (or the heart defibrillated in the two aforementioned cases).This was followed by gradual weaning from the cardiopulmonary bypass and wound closure after echocardiographic confirmation of successful valve repair.Table 4 summarizes the surgical details of all the patients.The median operative time was 230 (IQR, 200-255) minutes.The median CPB time was 144 (IQR, 124-152) minutes.The median ischemic time in patients who underwent aortic cross-clamping was 80 (IQR, 66-89) minutes.All valves were successfully repaired.There were no cases of valve replacement.There was no conversion to sternotomy and no intraoperative complications.

Postoperative Data Analysis
Table 5 summarizes the postoperative results.There was no case of postoperative low cardiac output requiring inotropic support or mechanical support or of myocardial infarction or postoperative stroke.Two patients developed postoperative delirium.One patient underwent re-thoracotomy for bleeding.Blood transfusion was needed in one patient perioperatively and in five patients during the postoperative period.One of the three patients who underwent ablation regained sinus rhythm, while the other two demonstrated persistent atrial fibrillation.No cases required permanent pacemaker implantation.One patient with postoperative sepsis was successfully treated with antibiotics with no further complications.The median ventilation time was 20 (IQR, 14-24) hours.The median duration of stay in intensive care was 3 (IQR, 2-4) days and the median duration of hospital stay was 8 (IQR, 8-11) days.There was no case of in-hospital mortality.The 30-day survival rate was 100%.

Discussion
Prospective randomized trials did not demonstrate a survival benefit of MIMVS over traditional surgery via sternotomy [1,2,5].However, previous studies did report better cosmetic results and shorter hospital stays with MIMVS over traditional surgery via sternotomy [1,2].As both factors are welcomed by both patients and clinicians, an increasing number of patients with mitral valve pathologies are undergoing the procedure via the minimally invasive approach [6][7][8][9]; over 50% of those who undergo isolated mitral valve surgery in Germany do so via the minimally invasive approach [9].
Although the recent guidelines on valvular heart disease recommend the CABG procedure in the presence of coronary heart disease (CHD) in patients with primary indications for aortic or mitral valve surgery, they recommend PCI in patients who undergo catheter-based intervention of either valve [3,10].These recommendations are understandable because the CABG procedure is favorable in patients who undergo sternotomy for the valve surgery and PCI is favorable in those who receive treatment percutaneously.Although previous reports have been published reporting favorable results of a hybrid concept consisting of PCI and MIMVS in different patient cohorts with mitral valve and coronary disease [11][12][13][14], there are no recommendations regarding the revascularization strategy in patients who might undergo MIMVS in the presence of adequate expertise.
In this study, we evaluated the decision-making process and results of this hybrid concept.The strategy of the heart team was to analyze CHD independent from the mitral valve pathology.If CHD was to be treated endovascularly according to the recent guidelines with no mitral valve pathology, this hybrid concept was suggested [3].The rationale behind this concept was to not deny the patient mitral valve repair via a favorable approach due to coronary pathology that would have been otherwise treated endovascularly with expected good results.Additionally, the rationale is also to facilitate the approach to the mitral valve in re-do procedures after a previous CABG with patent grafts where avoiding resternotomy is of special benefit to avoid graft injury.The results of this study demonstrate that this concept is a viable option in the presence of adequate expertise in MIMVS.Based on this study, we developed a simple decision-making flowchart to help in patient selection (Figure 1).
Another important aspect is the sequence of the procedures.On one hand, it might be surgically favorable to perform the surgical procedure before initiating double antiplatelet therapy (DPAT) after endovascular therapy for CHD because randomized controlled trials and retrospective studies have demonstrated higher rates of postoperative bleeding in patients on DPAT [15][16][17][18][19]. On the other hand, it is crucial to ensure adequate coronary perfusion before the surgery or at least ensure adequate myocardial protection with cardioplegia and avoid periprocedural myocardial infarction because previous publications have demonstrated a higher rate of perioperative myocardial infarctions in patients whose diseased coronary vessels were not addressed [20,21].In our study cohort, we generally opted to perform PCI first to also confirm the success of myocardial revascularization before MIMVS.
Regarding the optimum timeframe between PCI and MIMVS, the heart team unfortunately did not reach a consensus at the time of performing the procedures.Post-PCI clopidogrel therapy was stopped 5 days before the surgery in patients who were operated on after more than 30 days of PCI according to the ESC/EACTS guidelines [22].In patients with severe valvular symptoms who were operated on within 1 month of PCI, surgery was performed under DAPT.Our analysis did not demonstrate higher bleeding tendency in these patients.Furthermore, the analysis did not reveal periprocedural myocardial infarctions or low cardiac output syndrome, which reflect adequate myocardial perfusion and protection.Therefore, we believe that it is advisable to first address the CHD to ensure successful revascularization before surgery and to optimize myocardial protection during surgery.
The patients who had previously undergone CABG and were to undergo re-do surgery represented a special cohort.In the first patient, the heart team preferred to perform the mitral valve surgery first to avoid the bleeding tendencies in re-do situations.As the surgical team did not face increased bleeding tendency in this patient, the second patient underwent PCI first and then surgery, which was performed without complications.In hindsight, while believing that PCI should precede MIMVS, we also believe that it is advisable to plan PCI well before MIMVS to be able to safely stop DAPT before the surgery to decrease the bleeding risk without highly increasing the risk of stent thrombosis.This study has several limitations.It was a single center study that included a small number of patients, and procedures were not randomly assigned.To our knowledge, there are no previous studies that have evaluated the feasibility of hybrid PCI and MIMVS in similar cohorts.Therefore, further studies with larger patient numbers are required to corroborate the results of the present study and to draw more robust conclusions.Furthermore, the patient management protocol did not adhere to a standardized protocol regarding the timeframe between the procedures.Further studies should adhere to a standardized timeframe to provide clearer recommendations.Nevertheless, MIMVS This study has several limitations.It was a single center study that included a small number of patients, and procedures were not randomly assigned.To our knowledge, there are no previous studies that have evaluated the feasibility of hybrid PCI and MIMVS in similar cohorts.Therefore, further studies with larger patient numbers are required to corroborate the results of the present study and to draw more robust conclusions.Furthermore, the patient management protocol did not adhere to a standardized protocol regarding the timeframe between the procedures.Further studies should adhere to a standardized timeframe to provide clearer recommendations.Nevertheless, MIMVS might be more tolerant of DAPT with less restrictive indications for surgery under DAPT.This is yet to be confirmed in further studies.

Conclusions
A hybrid concept of PCI and MIMVS is feasible in patients with mitral valve pathology and single vessel coronary disease and can be considered if the team members have sufficient expertise in MIMVS.Future studies should also evaluate whether this recommendation is feasible for patients with multivessel disease, so that for patients with combined mitral valve and coronary pathologies, with the availability of adequate expertise in MIMVS, the choice of revascularization strategy can be evaluated independent from the mitral valve pathology.
Based on the results of this report, in centers with expertise in MIMVS, the coronary pathology and the choice revascularization strategy should be made independent from the mitral valve pathology.In patients whose coronary pathology is suitable for PCI, a hybrid PCI and MIMVS should be considered.
Abbreviations: NYHA: New York Heart Association; AICD: automated implantable cardioverter defibrillator; CABG: coronary artery bypass grafting; IQR: interquartile range; LIMA: left internal mammary artery; D1: the first diagonal branch; LAD: the left anterior descending artery; RIMA-T: the right internal mammary artery as a t-graft from the left internal mammary artery; M1: the first marginal branch of the circumflex artery; MIDCAB: minimally invasive direct coronary artery bypass; RCA: right coronary artery; RCX: circumflex artery.

Table 2 .
Preoperative EF and mitral valve pathology.