Results of minimally invasive, video-assisted mitral valve repair in advanced Barlow s disease with bileaflet prolapse

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1 European Journal of Cardio-Thoracic Surgery 47 (2015) doi: /ejcts/ezu166 Advance Access publication 7 May 2014 ORIGINAL ARTICLE Cite this article as: Muneretto C, Bisleri G, Bagozzi L, Repossini A, Berlinghieri N, Chiari E. Results of minimally invasive, video-assisted mitral valve repair in advanced Barlow s disease with bileaflet prolapse. Eur J Cardiothorac Surg 2015;47: Results of minimally invasive, video-assisted mitral valve repair in advanced Barlow s disease with bileaflet prolapse Claudio Muneretto a, *, Gianluigi Bisleri a, Lorenzo Bagozzi a, Alberto Repossini a, Nicola Berlinghieri b and Ermanna Chiari b a Division of Cardiac Surgery, University of Brescia Medical School, Brescia, Italy b Division of Cardiology, University of Brescia Medical School, Brescia, Italy * Corresponding author. Cardiochirurgia SSVD Spedali Civili, P.le Spedali Civili 1, Brescia, Italy. Tel: ; fax: ; munerett@med.unibs.it (C. Muneretto). Received 13 September 2013; received in revised form 16 January 2014; accepted 29 January 2014 Abstract OBJECTIVES: Minimally invasive mitral valve (MV) surgery has recently gained popularity as the standard approach for MV repair, albeit there could be potential concerns about the feasibility of complex repair in the presence of extreme Barlow s disease via a minimally invasive route. METHODS: Fifty consecutive patients with advanced Barlow s disease and bileaflet prolapse underwent minimally invasive, video-assisted MV repair via a 5 cm right antero-lateral thoracotomy with peripheral cannulation and external aortic clamping. Mean age, left ventricular ejection fraction and New York Heart Association class were 53 ± 11 years, 62 ± 7% and 3.1 ± 0.8, respectively. Logistic EuroSCORE (mean) was 3.1. Either Custodiol (36 patients; 72%) or crystalloid (14 patients; 28%) cardioplegia were utilized. Complete rings (CE Classic or Physio) were implanted. Chordal reimplantation was carried out by means of polytetrafluoroethylene (PTFE) chordae. RESULTS: All procedures were successfully performed with null/mild residual mitral regurgitation (MR) intraoperatively. A repair strategy of posterior leaflet resection and PTFE chordae implant (for anterior leaflet) or no-resect approach (only PTFE chordae on both leaflets) was performed in 62% (31 patients) and 38% (19 patients) of cases, respectively. Mean aortic cross-clamp and cardiopulmonary bypass times were 98 ± 23 and 131 ± 41 min, respectively. Hospital mortality was 0%. At a median follow-up of 761 days, 2 patients (4%) required reoperation (infective endocarditis: 1 patient; partial ring detachment: 1 patient) and valve rerepair was achieved in both. All patients are alive with a freedom from 2+ degree of MR of 100% at the latest echocardiographic evaluation. CONCLUSIONS: Minimally invasive approach for complex MV repair is feasible and safe and provided excellent early and mid-term results. Keywords: Barlow Mitral valve Valve repair Minimally invasive INTRODUCTION Barlow s disease still represents a surgical challenge due to the complexity of the mechanisms involved, namely voluminous excess of mitral valve (MV) leaflets and elongation, thickening or thinning of chordae tendinae [1, 2]. The high degree of expertise required in order to perform a successful MV repair in the presence of advanced Barlow s disease (involving both MV leaflets) often leads many surgeons and centres to prefer a replacement strategy to the repair one (up to 50% of cases), despite the widely proven advantages of the latter technique [3, 4]. Recently, the minimally invasive approach for MV surgery has gained popularity as the potentially preferred route for MV repair, given the safety and improved benefits (such as reduced trauma and earlier postoperative recovery) compared with the conventional approach via a median sternotomy [5 8]. Presented at the 27th Annual Meeting of the European Association for Cardio- Thoracic Surgery, Vienna, Austria, 5 9 October Notwithstanding the potential advantages of the minimally invasive approach, there could be potential concerns about the feasibility of a complex MV repair in the presence of extreme Barlow s disease via a minimally invasive route, which have been reported only by a limited number of authors to date [9]. We therefore aimed to evaluate in a prospective fashion the feasibility and durability of MV repair via a minimally invasive approach in this specific complex subset of patients with advanced Barlow s disease. MATERIALS AND METHODS Study population From January 2009 to March 2012, out of 165 patients requiring MV surgery, 50 consecutive patients with advanced Barlow s disease and scheduled to undergo minimally invasive MV surgery were prospectively enrolled in the study. The Author Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

2 C. Muneretto et al. / European Journal of Cardio-Thoracic Surgery 47 The inclusion criterion was the presence of Barlow s disease (billowing valve with thickened leaflets, elongated and thickened chordae, annular dilatation) involving both leaflets (with at least two segments involved per each leaflet or multisegment disease of the posterior leaflet plus A1 A2 or A2 A3 involvement); exclusion criteria were concomitant procedures (other than surgical ablation of atrial fibrillation), redo cases, urgent operations, chest wall deformities and severe atherosclerotic disease of the peripheral vessels. No patient exited from the study. Additional demographic details of the study population are outlined in Table 1: of note, mean age was 53 years with wellpreserved left ventricular ejection fraction (LVEF) and with a relatively low surgical risk profile (mean logistic EuroSCORE I = 3.1 ± 1.4). Operative techniques All patients enrolled in the study were scheduled to undergo minimally invasive video-assisted mitral surgery via a 5 cm right antero-lateral thoracotomy at the level of the fourth inter-costal space; excessive rib spreading was avoided by using a soft tissue retractor. Endoscopic vision was facilitated by means of 0 or 30 camera along with a full HD system (Karl Storz, Tuttlingen, Germany). Peripheral cannulation was utilized in all patients: arterial cannulation was performed by means of a femoral cannula (Fem-Flex II, Edwards Lifesciences, Irvine, CA, USA), while venous cannulation was performed via either a femoral vein cannula (VFem, Edwards Lifesciences, Irvine, CA, USA) and a jugular one (percutaneously inserted) or a two-stage femoral vein cannula (Carpentier model, Medtronic, Minneapolis, MN, USA) with vacuum assist if required. In all patients, arterial and venous cannulation was performed with Table 1: Preoperative patient characteristics Age (mean ± SD) (years) 53 ± 11 Gender (female) 19 (38%) Body mass index (mean ± SD) (kg/m 2 ) 23.9 ± 4.3 Family history for MR (any degree) 23 (46%) Hypertension 24 (48%) Hypercholesterolaemia 8 (16%) Renal failure (creatinine >2 mg/dl) 0 (0%) COPD 1 (2%) Peripheral artery disease 4 (8%) Previous cerebrovascular accidents 1 (2%) Dysthyroidism 5 (10%) Previous cardiac surgery 0 (0%) Atrial fibrillation 7 (14%) NYHA class (mean ± SD) 3.1 ± 0.8 Class I 2 (4%) Class II 6 (12%) Class III 27 (54%) Class IV 15 (30%) Ejection fraction (mean ± SD) 62 ± 7 Severe mitral regurgitation 49 (98%) Pulmonary hypertension 12 (24%) Logistic EuroSCORE I (mean ± SD) 3.1 ± 1.4 COPD: chronic obstructive pulmonary disease; NYHA: New York Heart Association. a Seldinger technique under transoesophageal echocardiography guidance as well as a centrifugal pump instead of a roller one. External aortic clamping by means of a flexible clamp (Cygnet, Vitalitec, Plymouth, MA, USA) was utilized in all instances. Cardioplegic arrest was achieved either via cold crystalloid or via Custodiol solution; in all instances, an antegrade route was utilized. The approach for MV exposure was via the Sondergaard s groove in all cases; CO 2 was actively insufflated inside the chest cavity throughout the surgical repair and intracardiac air removal achieved by means of ventricular filling and active aortic root suction. The MV repair techniques adopted were either by resection of the posterior mitral leaflet (PML) with sliding at the level of P2 and support of the anterior one with polytetrafluoroethylene (PTFE) chordae (Goretex chordae, Gore, Flagstaff, AZ, USA) or by a nonresectional approach with bileaflet support only by means of artificial neochordae. In all instances, annuloplasty was performed with complete rings, either Classic Carpentier-Edwards (Edwards Lifesciences, Irvine, CA, USA) or Physio rings (Edwards Lifesciences, Irvine, CA, USA). Intraoperative transoesophageal echocardiography was utilized in all cases in order to confirm the successful repair strategy (none or trivial regurgitation) and to facilitate deairing manoeuvres. In case of concomitant surgical ablation for atrial fibrillation, a complete isolation of all pulmonary veins and posterior aspect of the left atrium ( box lesion set) was performed by means of an epicardial, suction-based radiofrequency device (Cobra Adhere XL, Estech, San Ramon, CA, USA) before cardiopulmonary bypass had been instituted. Follow-up Follow-up visits at our institution were performed at 1, 6 and 12 months. Additional clinical data were collected from referring cardiologists and by telephone interview. All patients underwent echocardiography at least once per year. Statistical analysis Survival was evaluated by means of Kaplan Meier analysis. Continuous data are presented as mean ± standard deviation (SD); discrete variables have been reported in unit or percentages. The statistical package utilized was the SPSS software (IBM Corp. Released IBM SPSS Statistics for Windows, Version Armonk, NY, USA: IBM Corp.). RESULTS Intraoperative data Mean aortic cross-clamp and cardiopulmonary bypass (CPB) times were 98 ± 23 and 131 ± 41 min, respectively. Femoral artery cannulation was performed in all patients; venous cannulation with femoral and jugular vein cannula was utilized in 26 patients (52%), while a two-stage femoral vein cannula in the remaining 24 patients (48%). As previously outlined in the Methods section, a centrifugal pump was utilized in all cases rather than a conventional roller pump. Custodiol cardioplegic arrest was preferred in the majority of patients (n = 36, 72%). ADULT CARDIAC

3 48 C. Muneretto et al. / European Journal of Cardio-Thoracic Surgery Table 2: Intraoperative details Table 3: Postoperative data Cross-clamp time (mean ± SD) (min) 98 ± 23 Cardiopulmonary bypass time (mean ± SD) (min) 131 ± 41 Operation time (mean ± SD) (h) 4.3 ± 0.8 Arterial cannulation Femoral artery 50 (100%) Venous cannulation Right femoral 24 (48%) Right femoral and giugular 26 (52%) Cardioplegia Custodiol 36 (72%) Crystalloid 14 (28%) Ring type Classic 26 (52%) Physio (I, II) 24 (48%) Ring size (mean ± SD) (mm) 35 ± 3 Repair strategy Annuloplasty 50 (100%) PML resection + chordae on AML 31 (62%) No-resection strategy 19 (38%) Pulmonary veins ablation 4 (8%) Intra-operative echocardiography None mitral regurgitation 44 (88%) Trace/mild mitral regurgitation 6 (12%) PML: posterior mitral leaflet; AML: anterior mitral leaflet. Over half of the study population (n = 31, 62%) underwent MV repair by resecting the PML, P2 sliding and support of the anterior leaflet with PTFE chordae: on average, at least two loops of artificial chordae were placed. A non-resectional approach was utilized in 19 patients (38%) with artificial chordae being positioned on both leaflets (usually three to four loops on the posterior leaflet and two on the anterior one). Additional scallops between P1 P2 or P2 P3 were closed by means of 5/0 polypropylene sutures. In all instances, annuloplasty was performed with a complete ring of a relatively large size (mean = 35 ± 3 mm): a Classic ring was used in 26 patients (52%), while a Physio ring (either I or II) in the remaining 24 patients (48%). Of note, 14 patients received a size n 32 ring and 11 patients a size n 34 ring; finally, a size n 36, n 38 and n 40 was implanted in 10, 11 and 4 patients, respectively. Intraoperative echocardiography documented a successful repair in all cases, with no trace of residual mitral regurgitation in the majority of patients (44 patients, 88%) or a mild grade in 6 patients (12%). Concomitant surgical treatment of atrial fibrillation was performed by means of epicardial ablation in 4 patients (8%). Additional intraoperative details are provided in Table 2. Perioperative outcomes The occurrence of early postoperative complications as well as outcomes are outlined in Table 3. Of note, hospital mortality (within 30 days) in the current study population was 0%. Among perioperative complications, new-onset atrial fibrillation occurred in 16 patients (32%) while blood transfusions were required in 24 patients (48%). No patient required surgical revision for bleeding. The incidence of perioperative stroke, myocardial infarction or vascular access complications (at the site of peripheral Intubation time (mean ± SD) (h) 7.5 ± 5.4 Intensive care unit stay (mean ± SD) (h) 20.0 ± 8.7 Red blood cells units >2 24 (48%) Plasma transfusion 2 (4%) Platelets transfusion 1 (2%) Vascular complications 0 (0%) Pneumothorax 1 (2%) Arrhythmias Atrial fibrillation (new onset) 16 (32%) Junctional rhythm (transient) 1 (2%) Exploration for bleeding 0 (0%) Endocarditis 1 (2%) Stroke 0 (0%) Myocardial infarction 0 (0%) Hospital mortality 0 (0%) Time to discharge (mean ± SD) (days) 4.9 ± 3.3 Table 4: Mid-term follow-up Median follow-up (days) 761 Reoperation 2 (4%) Freedom from 2+ degree of mitral regurgitation 50 (100%) Ejection fraction (mean ± SD) 60 ± 5 Stroke 0 (0%) Myocardial infarction 0 (0%) cannulation) was also 0%. Moreover, no case of aortic dissection due to retrograde flow was recorded in the current series. No cases of permanent heart block requiring PM implantation were recorded; also, there were no wound complications observed in the current series. One patient suffered from postoperative endocarditis requiring early reoperation with surgery being performed within 30 days via the same minimally invasive route and with a repair strategy being successfully accomplished. Mean postoperative hospital stay was 4.9 ± 3.3 days. Mid-term follow-up At a median follow-up of 761 days (range: ) (Table 4), clinical and echocardiographic evaluation could be performed in all patients as outlined in the Methods section. Reoperation was required in 2 patients (4%): as previously depicted, 1 patient suffered from acute infective endocarditis during the early postoperative period; in the other instance, partial ring detachment occurred 1 year postoperatively. Both patients underwent redo surgery via a minimally invasive approach and a successful repair strategy could be carried out in both cases. At mid-term follow-up all patients are alive with a freedom from 2+ degree of MR of 100% at the latest echocardiographic

4 C. Muneretto et al. / European Journal of Cardio-Thoracic Surgery 49 Figure 1: Kaplan Meier estimate for freedom from reoperation. CI: confidence interval. Figure 2: Kaplan Meier estimate for freedom from symptoms (NYHA 2). CI: confidence interval. evaluation; also, mean postoperative left ventricular ejection fraction (LVEF) was preserved in the follow-up period (60 ± 5%) (Table 4). Kaplan Meier survival free from reoperation is 95.7% (95% confidence interval (CI) = %) (Fig. 1), while freedom from recurrent symptoms (New York Heart Association (NYHA) class 2) is 91.0% (95% CI: %) (Fig. 2). DISCUSSION The trend towards the use of less invasive surgical procedures has significantly influenced the evolution of techniques and technologies for MV surgery over the past decade. Minimally invasive MV surgery via a limited antero-lateral thoracotomy and under videoscopic support is nowadays a well-established approach and it has been proved to be associated with reduced rate of postoperative complications (such as need for reoperation for bleeding, overall shorter hospital stay), durability of the repair on long-term outcomes equivalent to that of the conventional approach and improved outcomes in terms of reduced postoperative pain, wound infections and better cosmesis [5]. The technical complexity of MV repair in presence of advanced Barlow s disease (involving both leaflets) has often discouraged surgeons to adopt a repair strategy while opting for a MV replacement instead, despite the excellent outcomes at long-term following MV repair in Barlow s disease when performed by experienced operators [3, 10]. The possibility to carry out an MV repair strategy via a minimally invasive route is therefore intriguing, albeit poorly investigated to date [9]. In our study, 50 consecutive patients with advanced Barlow s disease were prospectively enrolled to undergo minimally invasive MV repair and followed up to 2 years in order to assess the safety, efficacy and durability of a less invasive approach in this specific subset of patients. Our study population had a low-risk surgical profile (Logistic EuroSCORE I = 3.1 ± 1.4): it was relatively young (mean age 53 ± 11 years) with almost no relevant comorbities other than hypertension (24 patients, 48%) and no redo cases; moreover, left ventricular ejection fraction was within normal ranges (LVEF = 62 ± 7%). Of note, almost half of the enrolled patients (23 patients, 46%) had a family history of mitral regurgitation: in fact, Barlow s disease affects up to 5% of the general population and despite being considered sporadic in the majority of instances, a potential autosomal dominant inheritance has been suggested [11], albeit any kind of genetic testing was outside the scope of the present study. The repair strategy adopted in the current series consisted of either a more classical approach based on a wide resection of the PML with sliding and support of the anterior mitral leaflet with neochordae or a non-resectional approach (implying bileaflet support with artificial chordae). Although the use of a nonresectional approach may potentially lead to an increased risk of systolic anterior motion (SAM) due to excessive leaflets billowing if the length of the artificial chordae are not properly adjusted [2, 12], we did not observe any case of SAM in our current series. Of note, there was a trend in recent years towards a non-resectional approach (with exclusive use of bileaflet support by means of neochordae), albeit the limited number of patients enrolled in the current study as well as the follow-up duration did not allow a comparison among the two repair strategies. As previously reported in the literature [2], annuloplasty was not aimed at achieving undersize of the mitral annulus, especially in the population with no-resectional approach; in all instances, a complete ring was utilized. Similar to other reports [5, 9], mean aortic cross-clamp and CPB times (98 and 131 min, respectively) were relatively longer compared with a conventional approach, albeit no direct comparison with a population undergoing MV repair via sternotomy was performed in the current study. Moreover, also the overall operative time is consistent with previously published series [9, 13]. There was no hospital mortality among the limited number of patients enrolled in the current study, which reflects the safety of the minimally invasive approach as demonstrated by previously published larger series [6 8]. Among postoperative complications, we did not observe any case of vascular access complications nor iatrogenic dissection related to retrograde flow during CPB as previously reported [14]: however, other studies failed to precisely disclose the technique utilized for peripheral vessel cannulation or the type of pump for CPB. In our series, even when the peripheral vessels had been surgically exposed, cannulation was performed exclusively using the Seldinger technique under transoesophageal guidance in order to verify the proper intravascular position of the guidewire; moreover, a centrifugal pump was ADULT CARDIAC

5 50 C. Muneretto et al. / European Journal of Cardio-Thoracic Surgery preferred in all instances to a roller one in order to immediately detect any potential change in pump blood flow. There were also no cases of stroke during the early postoperative period: this may be related in first instance to the relatively young age of the study population, albeit the use of transthoracic flexible clamp instead of an endo-clamping technique may have accounted for such results as previously reported [15]. Among other postoperative complications, there was a relatively higher rate of blood transfusions in our series (24 patients, 48%) compared with previously published reports [5 7]: the extensive use of custodiol cardioplegia in the current study population (36 patients, 72%) may have accounted for such result. In fact, a higher volume of cardioplegia is usually required when administering a single dose such as with the Custodiol solution in order to ensure complete cooling and distribution to all myocardial territories [16], which in turn may lead to higher degree of haemodilution. In fact, also in our study population, there was a considerable difference in terms of transfusion rate among patients receiving crystalloid (2 of 14 patients, 14%) and custodiol cardioplegia (22 of 36 patients, 61%). We recently implemented a protocol of routine haemofiltration during CPB and cardioplegic administration of Custodiol in order to reduce this potential drawback of the Custodiol solution. In fact, we believe that the Custodiol solution represents a useful tool during minimally invasive MV surgery, since the single administration avoids the drawback related to the need for removing and reposition of the left atrial retractor during additional shots typically required with the use of other kinds of cardioplegia. At mid-term follow-up, all patients but 2 (48 patients, 96%) were free from reoperation, confirming an excellent survival free from reoperation and symptoms, despite the high degree of complexity of the MV disease. In conclusion, despite the limitations of the current analysis mainly related to the small sample size and the relatively short follow-up time, our study demonstrates that the minimally invasive approach for complex MV repair is feasible and safe while providing excellent early and mid-term results. In our centre, over the past decade we developed a large experience with repair techniques of complex Barlow s MV disease, which accounts for 20% of our case volume nowadays; similarly, there has been a growing trend towards a larger percentage of patients being treated with less invasive technique at our institution: in the early 2000s, more simple cases (such as isolated P2 prolapse) received a minimally invasive approach, and since 2009, this approach has been utilized in all-comers, including patients with complex MV pathology, such as Barlow s disease. Therefore, this approach requires either an established experience in minimally invasive techniques as well as in repair strategies for complex MV disease. In conclusion, we believe that our preliminary results should encourage experienced centres in a more extensive use of repair approaches via a less invasive route also in such complex subset of patients. Funding None. Conflict of interest: none declared. REFERENCES [1] Barlow JB, Pocock WA, Marchand P, Denny M. The significance of late systolic murmurs. Am Heart J 1963;66: [2] Anyanwu AC, Adams DH. Etiologic classification of degenerative mitral valve disease: Barlow s disease and fibroelastic deficiency. Semin Thorac Cardiovasc Surg 2007;19:90 6. [3] Adams DH, Rosenhek R, Falk V. Degenerative mitral valve regurgitation: best practice revolution. Eur Heart J. 2010;31: [4] Iung B, Baron G, Butchart EG, Delahaye F, Gohlke-Bärwolf C, Levang OW et al. A prospective survey of patients with valvular heart disease in Europe: The Euro Heart Survey on Valvular Heart Disease. Eur Heart J 2003;24: [5] Modi P, Hassan A, Chitwood WR Jr. Minimally invasive mitral valve surgery: a systematic review and meta-analysis. Eur J Cardiothorac Surg 2008;34: [6] McClure RS, Cohn LH, Wiegerinck E, Couper GS, Aranki SF, Bolman RM 3rd et al. Early and late outcomes in minimally invasive mitral valve repair: an eleven-year experience in 707 patients. J Thorac Cardiovasc Surg 2009;137: [7] Goldstone AB, Atluri P, Szeto WY, Trubelja A, Howard JL, MacArthur JW Jr et al. Minimally invasive approach provides at least equivalent results for surgical correction of mitral regurgitation: a propensity-matched comparison. J Thorac Cardiovasc Surg 2013;145: [8] Seeburger J, Borger MA, Falk V, Kuntze T, Czesla M, Walther T et al. Minimal invasive mitral valve repair for mitral regurgitation: results of 1339 consecutive patients. Eur J Cardiothorac Surg 2008;34: [9] Speziale G, Nasso G, Esposito G, Conte M, Greco E, Fattouch K et al. Results of mitral valve repair for Barlow disease (bileaflet prolapse) via right minithoracotomy versus conventional median sternotomy: a randomized trial. J Thorac Cardiovasc Surg 2011;142: [10] Flameng W, Meuris B, Herijgers P, Herregods MC. Durability of mitral valve repair in Barlow disease versus fibroelastic deficiency. J Thorac Cardiovasc Surg 2008;135: [11] Disse S, Abergel E, Berrebi A, Houot AM, Le Heuzey JY, Diebold B et al. Mapping of a first locus for autosomal dominant myxomatous mitral-valve prolapse to chromosome 16p11.2-p12.1. Am J Hum Genet. 1999;65: [12] Ibrahim M, Rao C, Athanasiou T. Artificial chordae for degenerative mitral valve disease: critical analysis of current techniques. Interact CardioVasc Thorac Surg 2012;15: [13] Dogan S, Aybek T, Risteski PS, Detho F, Rapp A, Wimmer-Greinecker G et al. Minimally invasive port access versus conventional mitral valve surgery: prospective randomized study. Ann Thorac Surg 2005;79: [14] Murzi M, Cerillo AG, Miceli A, Bevilacqua S, Kallushi E, Farneti P et al. Antegrade and retrograde arterial perfusion strategy in minimally invasive mitral-valve surgery: a propensity score analysis on 1280 patients. Eur J Cardiothorac Surg 2013;43:e [15] Grossi EA, Loulmet DF, Schwartz CF, Solomon B, Dellis SL, Culliford AT et al. Minimally invasive valve surgery with antegrade perfusion strategy is not associated with increased neurologic complications. Ann Thorac Surg 2011;92: [16] Viana FF, Shi WY, Hayward PA, Larobina ME, Liskaser F, Matalanis G. Custodiol versus blood cardioplegia in complex cardiac operations: an Australian experience. Eur J Cardiothorac Surg 2013;43: APPENDIX. CONFERENCE DISCUSSION Dr P. Perier (Bad Neustadt/Saale, Germany): I would like to acknowledge the good results - 50 patients, no deaths, 100% repair and 100% freedom from MR >2+ at two years - presented here. I have some questions, nevertheless, and the first one is regarding the title. I am a very simple man. I have some difficulty in understanding or defining Barlow s disease, because in the literature we repeat this term over and over and there is no clear definition. Not only do you use this term, but you invent a kind of new entity, which is advanced or extreme, and I don t know what this is. So maybe you will be kind enough to explain it to us. Second, I had the opportunity to read your manuscript, and in your manuscript you said that the mean size of the ring that you use is 35, and I am amazed, because I guess that you are referring to patients with a huge excess of tissue of all the segments of the mitral valve, and usually I would think that you would put a ring size 40 in all these patients, and I think that a mean size of ring of 35 is relatively small. My other question, because it is really different from our experience, is regarding the rate of transfusion that you have of 48%. Unfortunately, it doesn t speak very well for minimally invasive surgery, because in the EVEREST trial where we can discuss the quality of surgery, much of our repair through sternotomy has a rate of transfusion of 52%. So 48% is almost equivalent. We have

6 C. Muneretto et al. / European Journal of Cardio-Thoracic Surgery 51 7%. You say that it is due to haemodilution. Could you elaborate on this a little bit more? Dr Muneretto: First of all, you have already said that, from the literature, you do not understand what Barlow s disease is because of the lack of a clear definition. For this reason, people may consider Barlow s disease as a very simple disease of the mitral valve involving both leaflets. We use the extreme Barlow s disease definition to explain that all those patients have a deep disease diffused to all the components of the valve. Therefore, in extreme Barlow s, we consider it to be not a simple bileaflet prolapse, but all those patients showing diffuse disease of both the leaflets for at least two components, for example, P1-P2, A1-A2. Regarding the second question about the size of the ring, if you look at the BMI of our patients, they are considerably smaller when compared to the US population or even to other European countries. This is a characteristic of the Mediterranean countries, including Spain and Greece. I think that you should consider the mean size of the ring in relation to the BMI. The mean patient BMI was 22, and that is perfectly related to a 35 mean size of ring. The rate of transfusion, of course, was very high. But this event was not related to bleeding but to our policy to maintain haematocrit levels higher than 28 in extracorporeal circulation. The reason why we run CPB with a haemotcrit level higher than 28 is related to the need for early extubation, maintaining normal values of ph and lactate during the operation. Of course, this policy increases the rate of transfusion, but avoiding haemodilution reduces ventilation time and postoperative complications. I do not believe that minimally invasiveness should be related to the rate of transfusions per se. It could be related if the rate of transfusion is caused by bleeding, but that was not the case in our study. Dr P. Kappetein (Rotterdam, Netherlands): Claudio, did these results include your learning curve for this technique or were these patients in the later part of your series of minimally invasive mitral surgery? Dr Muneretto: The answer is no. We started our experience with the Heartport system in the early 90s, and our learning curve in those techniques was completed several years ago. Of course, when we started the minimally invasive mitral valve approach, we didn t include such challenging patients. These are the results of the last 15-year experience in minimally invasive mitral valve surgery. Dr V. Falk (Zürich, Switzerland): I have one technical question. You were mentioning that in half of the patients a double-stage venous cannula was used and in the other half separate SVC drainage was applied using a jugular vein cannula. So what was the rationale behind the decision to use different venous drainage strategies? Dr Muneretto: The reason is very simple. Only two surgeons are involved in this surgery. I prefer two cannulas and the other surgeon prefers the doublestage cannula. I can explain the reason why I prefer two cannulas. First, I believe that the snaring of both venae cavae improves myocardial protection and provides a bloodless operative field. By using guide wire techniques through the oblique and transverse sinuses, it is very easy to control SVC and IVC in a minimally invasive approach. In addition, two cannulas plus caval snaring may be helpful in reducing the rate of transfusion, since we can drain the cardioplegia efflux from the right atrium, avoiding an excess in haemodilution. ADULT CARDIAC