Aortic valve replacement for severe aortic regurgitation in asymptomatic patients with normal ejection fraction and severe left ventricular dilatation

Transcription

1 Interactive CardioVascular and Thoracic Surgery 22 (2016) doi: /icvts/ivv365 Advance Access publication 30 December 2015 ORIGINAL ARTICLE ADULTCARDIAC Cite this article as: Wang Y, Shi J, Li F, Wang Y, Dong N. Aortic valve replacement for severe aortic regurgitation in asymptomatic patients with normal ejection fraction and severe left ventricular dilatation. Interact CardioVasc Thorac Surg 2016;22: Aortic valve replacement for severe aortic regurgitation in asymptomatic patients with normal ejection fraction and severe left ventricular dilatation Yin Wang, Jiawei Shi, Fei Li, Yongjun Wang and Nianguo Dong* Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China * Corresponding author. Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China, 1277, Jiefang Avenue, Wuhan, Hubei , China. Tel: ; dongnianguo@hotmail.com (N. Dong). Received 30 July 2015; received in revised form 18 November 2015; accepted 25 November 2015 ORIGINAL ARTICLE Abstract OBJECTIVES: According to current guidelines, aortic valve surgery is a Class II indication for asymptomatic patients with severe aortic regurgitation (AR) accompanied by left ventricular (LV) ejection fraction (LVEF) 50% and left ventricular end-diastolic dimension (LVEDD) >70 mm. This study aims to assess the postoperative outcomes of asymptomatic patients with severe AR accompanied by LVEF 50% and LVEDD >70 mm after aortic valve replacement (AVR) and to identify prognostic indicators of the surgery, especially in terms of LV ejection fraction and degree of LV dilatation. METHODS: We retrospectively identified 192 consecutive asymptomatic patients with severe AR accompanied by LVEF 50% and LVEDD > 70 mm who underwent isolated AVR from January 2003 to December Postoperative outcomes and prognostic indicators were evaluated and analysed. RESULTS: Patients had a mean age of 52.4 ± 16.1 years, and 69.3% were male. The mean LVEF and the mean LVEDD were 58.6 ± 6.6% and 76.0 ± 6.9 mm, respectively. The in-hospital mortality rate was 2.1% and survival rates at 5 and 10 years were 94.5 and 86.6%, respectively. Multivariable analysis indicated that postoperative mortality was associated with age [hazard ratio (HR) 1.059, 95% confidence interval (CI): , P = 0.049], preoperative LVEF (HR % CI: , P = 0.035) and LVEDD (HR % CI: , P = 0.032). Receiver-operating characteristic analysis showed that preoperative LVEF < 55% and LVEDD 81 mm were the best cut-off values for predicting postoperative mortality. By subgroup analysis, patients with 50 LVEF < 55% had poorer 5- and 10-year survival rates of 87.4 and 74.8% compared with 97.3% and 91.7% for patients with LVEF 55% (P = 0.023). Patients with LVEDD 81 mm had poorer 5- and 10-year survival rates of 85.6 and 72.6% compared with 98.2% and 85.6% for those with LVEDD < 81 mm (P = 0.027). CONCLUSIONS: AVR can be performed with satisfactory outcomes for severe aortic regurgitation in asymptomatic patients with severe AR accompanied by LVEF 50% and LVEDD > 70 mm. It is observed that 50% LVEF < 55% or LVEDD 81 mm are associated with poorer prognosis in patients undergoing AVR. Keywords: Aortic valve replacement Asymptomatic Aortic regurgitation Left ventricular ejection function Left ventricular enddiastolic dimension INTRODUCTION Aortic regurgitation (AR) is characterized by left ventricular (LV) volume overload leading to LV compensatory dilatation and hypertrophy. However, left ventricular ejection fraction (LVEF) may be in the normal range [1]. Most of these patients are asymptomatic with normal LVEF, but have an extremely enlarged left ventricle [2]. According to 2014 American College of Cardiology/ American Heart Association guidelines, normal LV systolic function(lvef 50%) accompanied by progressive LV dilatation (left ventricular end-diastolic dimension, LVEDD > 65 mm) is considered as a Class IIb indication for aortic valve surgery in asymptomatic patients with severe AR if the surgical risk is low [3]. Meanwhile, 2012 European Society of Cardiology/European Association for Cardio-Thoracic Surgery guidelines for a Class IIa recommendation suggest aortic valve surgery in asymptomatic patients with severe AR accompanied by LVEF 50% and LVEDD > 70 mm [4]. Severe LV dilatation is almost always the result of excessive LV volume caused by AR. Although LV systolic function is impaired in these cases, LVEF is within the normal range [5]. However, few studies have reported the prognosis of aortic valve replacement (AVR) in asymptomatic patients with severe AR accompanied by LVEF 50% and LVEDD > 70 mm, and no study has evaluated the impact of preoperative clinical characteristics on postoperative The Author Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

2 426 Y. Wang et al. / Interactive CardioVascular and Thoracic Surgery survival in such patients. This study assessed the postoperative outcomes of asymptomatic patients with severe AR accompanied by LVEF 50% and LVEDD > 70 mm after AVR. We sought to identify prognostic indicators for such patients undergoing AVR, especially in terms of LV ejection fraction and degree of LV dilatation. PATIENTS AND METHODS This retrospective cohort study reviewed 192 consecutive asymptomatic patients with severe AR accompanied by LVEF 50% and LVEDD > 70 mm who underwent isolated AVR between January 2003 and December 2013 at the department of cardiovascular surgery of Wuhan Union Hospital, China. All included patients received transthoracic echocardiographic (TTE) examination and were diagnosed with severe AR. Asymptomatic was defined as having no typical cardiac symptoms, such as exertional chest pain, dyspnoea on exertion, dyspnoea at rest, paroxysmal nocturnal dyspnoea or orthopnoea. Initially, we retrieved 2612 consecutive patients who underwent AVR from our database. Of these, 378 patients with severe AR were asymptomatic having LVEF 50% and LVEDD > 70 mm; we excluded 41 patients who had moderate or greater aortic stenosis, 88 patients who had concomitant coronary artery bypass grafting or mitral valve surgery or aortic root surgery and treatment of congenital heart disease, 38 patients with previous surgery and 19 patients with acute AR, including aortic dissections or infective endocarditis. All patients received TTE examination within 3 months before AVR. The degree of AR (Grade 3 or 4) was determined by Doppler ultrasonography. Preoperative clinical characteristics, operation variables and postoperative in-hospital mortality were acquired from the medical records. Patients were followed up by telephone interview and clinic re-examination. Completeness of follow-up was 94.7% with a median of 67 months (mean: 64 ± 46 months). The major outcome measures were postoperative mortality and long-term survival. The Statistical Package for Social Sciences, version 19.0 (SPSS) and GraphPad Prism 6 were used for data storage and analysis with P < 0.05 as the criterion for significance. Continuous variables are reported as the mean standard deviation and categorical variables as percentages. Continuous variables were compared using Student s t-tests, and categorical variables were compared using Fisher s exact tests. The life-table method was used to evaluate the long-term survival of the overall cohort. Kaplan Meier analysis was used to determine the survival rate, and the difference between groups was analysed using the log-rank test. Univariable and multivariable models were created using logistic regression for binary outcomes and Cox proportional hazards for time-related data. The Forward Wald stepwise procedure was applied to build the multivariable Cox regression model. Variables with P-values <0.10 in univariate analyses were candidates for the multivariable Cox regression analysis. Receiver-operating characteristic curve (ROC) analysis was used to evaluate cut-off values of independent continuous variables for predicting mortality by calculating the area under the ROC. The cut-off values of LVEF and LVEDD were calculated corresponding to the maximum area under the ROC. RESULTS Preoperative and operative characteristics The overall cohort consisted of 192 asymptomatic patients with severe AR accompanied by LVEF 50% and LVEDD > 70 mm; the mean age was 52.4 ± 16.1 years, and 69.3% were male. Of the total, 15.1% of the patients had been diagnosed with atrial fibrillation, 5.2% with diabetes mellitus and 16.7% with hypertension. The mean LVEF was 58.6 ± 6.6% and the mean LVEDD was 76.0 ± 6.9 mm; 88.5% of the patients received mechanical prostheses replacement. Preoperative characteristics are summarized in Table 1. In-hospital mortality and long-term survival There were 4 in-hospital deaths (2.1%) caused by low cardiac output syndrome (2 patients), multiple organ failure (1 patient) and haemorrhage (1 patient). Among the discharged patients, 178 patients have been followed up. During the follow-up period, 10 patients (5.6%) died of various causes, including 6 cardiac-related deaths (congestive heart failure in 5 patients, arrhythmia in 1 patient), 3 anticoagulation-related deaths (haemorrhage in 2 patients, thromboembolism in 1 patient) and 1 sudden death. Five- and 10-year survival estimates were 93.3 and 86.4%, respectively (Fig. 1). Preoperative and postoperative echocardiographic variables are given in Table 2. Risk factor analyses for postoperative mortality On univariable Cox regression analyses, univariable and multivariable predictors of postoperative mortality included age [hazard ratio (HR) Table 1: Preoperative and operative characteristics of the overall cohort (n = 192) Variables Overall cohort Clinical variables Age (years) 52.4 ± 16.1 Male 133 (69.3%) Hypertension 32 (16.7%) Diabetes mellitus a 10 (5.2%) Hypohepatia b 6 (3.1%) Renal insufficiency c 5 (2.6%) COPD 21 (10.9%) Atrial fibrillation 29 (15.1%) Echocardiography LVEF (%) 58.6 ± 6.6 LVFS (%) 29.3 ± 6.4 LVEDD (mm) 76.0 ± 6.9 Left atrial diameter (mm) 47.7 ± 11.4 Interventricular septal thickness (mm) 11.4 ± 1.3 Posterior wall thickness (mm) 10.5 ± 1.2 Operation variables Mechanical/bioprosthetic valve 170 (88.5%)/22 (11.5%) Perfusion time (min) 96.3 ± 34.2 Cross-clamp time (min) 57.1 ± 25.2 Mechanical ventilation time (h) 37.9 ± 24.5 Postoperative variables In-hospital mortality 4 (2.1%) Follow-up mortality 10 (5.6%) a Defined as the patients need to be managed by oral or insulin therapy. b Defined as ALT >2 upper limit of normal (40 U/l). c Defined as dialysis dependency. COPD: chronic obstructive pulmonary disease; LVEF: left ventricular ejection fraction; LVFS: left ventricular fractional shortening; LVEDD: left ventricular end-diastolic dimension; ALT: alanine transaminase.

3 Y. Wang et al. / Interactive CardioVascular and Thoracic Surgery 427 for the 50 LVEF < 55% group and 97.3 and 91.7% for the LVEF 55% group, respectively (Fig. 4). LVEDD 81 mm was also associated with a lower survival (P = 0.027). 5- and 10-year survival estimates were 98.2 and 85.6% for the 70 mm < LVEDD < 81 mm group and 85.6 and 72.6% for the LVEDD 81 mm group, respectively (Fig. 5). DISCUSSION Figure 1: Survival curve of asymptomatic patients with severe AR accompanied by LVEF 50% and LVEDD >70 mm after AVR. AR: aortic regurgitation; LVEF: left ventricular ejection fraction; LVEDD: left ventricular end-diastolic dimension; AVR: aortic valve replacement. Table 2: variables Preoperative and postoperative echocardiographic Variable Preoperatively Postoperatively 1 week 6 months 3 years LVEF (%) 57.6 ± ± ± ± 5.9 LVFS (%) 29.3 ± ± ± ± 4.7 LVEDD (mm) 76.0 ± ± ± ± 6.5 LVEF: left ventricular ejection fraction; LVFS: left ventricular fractional shortening; LVEDD: left ventricular end-diastolic dimension , 95% confidence interval (CI): , P = 0.042], preoperative hypohepatia (HR 1.492, 95% CI: , P = 0.056), chronic obstructive pulmonary disease (HR 1.980, 95% CI: , P = 0.074), LVEF (HR % CI: , P = 0.011), LVFS (HR % CI: P = 0.021) and LVEDD (HR % CI: P = 0.003). On multivariable Cox regression analyses, three factors in the model predicted postoperative mortality, including age (HR 1.059, 95% CI: , P = 0.049), preoperative LVEF (HR % CI: , P = 0.035) and LVEDD (HR % CI: , P = 0.032) (Table 3). Best cut-off values of left ventricular ejection fraction and left ventricular end-diastolic dimension for predicting postoperative mortality Using receiver-operating characteristics curves, we found that the best cut-off values for predicting postoperative mortality after AVR for asymptomatic patients with severe AR accompanied by LVEF 50% and LVEDD > 70 mm were 55% for preoperative LVEF and 81 mm for preoperative LVEDD (Figs 2 and 3). It was found that 50% LVEF < 55% was associated with a lower survival (P = 0.023); five- and 10-year survival estimates were 87.4 and 74.8% The major findings of our study on asymptomatic patients with severe AR accompanied by LVEF 50% and LVEDD > 70 mm undergoing isolated AVR were as follows: (i) AVR can be performed with satisfactory outcomes for asymptomatic patients with severe AR accompanied by LVEF 50% and LVEDD > 70 mm. (ii) Age, LV systolic function and degree of LV dilatation were found to be preoperative indicators of postoperative survival in such patients after AVR. (iii) The best preoperative cut-off value of LVEF or LVEDD to predict postoperative mortality was 55% or 81 mm. (iv) In the subgroup of patients categorized by values of preoperative LVEF or LVEDD, asymptomatic patients with severe AR accompanied by LVEF 50% and LVEDD > 70 mm have a poorer prognosis after AVR if preoperative LVEF < 55% or LVEDD 81 mm. Current guidelines propose that AVR may be considered for asymptomatic patients with severe AR and normal LV systolic function [LVEF > 50%, but with severe LV dilatation (LVEDD > 70 mm)] [3, 4]. However, the guidelines suggested that patients with preserved LVEF and enlarged LV chamber size were at a higher risk of sudden death, basing on two previous reports with a small number of patients [6, 7]. To our knowledge, few studies have reported postoperative outcomes and evaluated prognostic factors of AVR for asymptomatic patients with normal ejection fraction and severe LV dilatation. Our study showed that the in-hospital mortality rate was 2.1%, and 5- and 10-year survival rates were 94.5 and 86.6% for the overall cohort after AVR, respectively. Patients in our study had a better clinical outcome than most prior published series that focused on patients with severe AR regardless of LV systolic function and LV dilatation [8 11]. The reasons of the better clinical outcome may be the younger age and better cardiac function of our patient population. Moreover, different from some other studies, only patients undergoing isolate AVR were chosen into our cohort in order to minimize the influence of other concomitant cardiac surgeries on the postoperative outcomes. For example, Turk et al. [8] published a retrospective study that evaluated 123 patients with chronic severe AR and a mean follow-up period of 4.8 years. The study population was older with a mean age of 60 years and patients with concomitant coronary artery bypass graft surgery were not excluded. The 5- and 10-year survival rates after AVR of their cohort were 83 and 67%, respectively. Chaliki et al. [8] studied 450 patients with a mean age of 57 years who underwent surgery for AR and were followed for a median duration of follow-up of 8.1 years. The overall operative mortality rate was 5.5% and survival rates were 82±2and63±3%at5and10years,respectively. Preoperative impaired LV systolic function has been reported to be a poor prognostic factor in patients with severe AR undergoing AVR, but the definition of impaired LV systolic function is less clear. According to STS Risk Estimate and EuroSCORE, preoperative LVEF < 50% is a risk factor that indicates poorer outcomes of patients undergoing cardiac surgery [12, 13], whereas some previous studies have evaluated the influence of preoperative LVEF on the prognosis of asymptomatic AR patients after AVR by choosing or ORIGINAL ARTICLE

4 428 Y. Wang et al. / Interactive CardioVascular and Thoracic Surgery Table 3: Univariate and multivariate Cox regression analyses for predicting postoperative mortality after AVR in asymptomatic patients with severe AR accompanied by LVEF 50% and LVEDD > 70 mm Variables Univariate Multivariate HR (95% CI) P-value HR (95% CI) P-value Age (years) ( ) ( ) Males ( ) Hypertension ( ) Diabetes mellitus ( ) Hypohepatia ( ) Renal insufficiency ( ) COPD ( ) Atrial fibrillation ( ) LVEF (%) ( ) ( ) LVFS (%) ( ) LVEDD (mm) ( ) ( ) Left atrial diameter (mm) ( ) Interventricular septal thickness (mm) ( ) Posterior wall thickness (mm) ( ) COPD: chronic obstructive pulmonary disease; LVEF: left ventricular ejection fraction; LVFS: left ventricular fractional shortening; LVEDD: left ventricular end-diastolic dimension; CI: confidence interval; HR: hazard ratio; AVR: aortic valve replacement; AR: aortic regurgitation. Figure 2: Receiver-operating characteristic curve analysis of LVEF for predicting mortality after AVR in asymptomatic patients with severe AR accompanied by LVEF 50% and LVEDD >70 mm. AUC: area under the curve; CI: confidence interval; AR: aortic regurgitation; LVEF: left ventricular ejection fraction; LVEDD: left ventricular end-diastolic dimension; AVR: aortic valve replacement. Figure 3: Receiver-operating characteristic curve analysis of LVEDD for predicting mortality after AVR in asymptomatic patients with severe AR accompanied by LVEF 50% and LVEDD >70 mm. AUC: area under the curve; CI: confidence interval; AR: aortic regurgitation; LVEF: left ventricular ejection fraction; LVEDD: left ventricular end-diastolic dimension; AVR: aortic valve replacement. categorizing patients based on preoperative LVEF values [9, 14 16]. For example, Scognamiglio et al. [14] showed a stratified outcome in 266 patients with asymptomatic AR and LVEF < 50% who underwent AVR. Five- and 10-year survival rates were 94 and 78 85%, respectively. In our cohort, patients with LVEF 55% had a better survival benefit compared with those with 50 LVEF < 55%. Fiveand 10-year survival rates were 97.3 and 91.7% for patients with LVEF 55%; however, they were only 87.4 and 74.8% for those with 50 LVEF < 55%, respectively. Severe LV dilatation is the result of excessive LV volume caused by AR; and the left ventricle becomes compensatory eccentric hypertrophic with cardiomyocyte enlargement and decreased contraction protein content [17]. Because cardiac work efficiency decreases and the oxygen consumption increases, LVEF and LVFS pseudo-increases within the normal range, but LV systolic function has actually been impaired [5]. Therefore, we consider the LV systolic function to be impaired when asymptomatic patients have severe AR and LV dilatation even though the value of LVEF measured by echocardiography is above 50%. The best preoperative LVEF cut-off value to predict postoperative outcomes in such asymptomatic patients is 55%. The other prognostic factor we evaluated was larger left ventricular end-diastolic dimension (LVEDD 81 mm), and found that it should be considered in assessing the postoperative outcomes of asymptomatic patients accompanied by LVEF 50% and LVEDD > 70 mm. Although some studies have reported LV dimensions to be the predictive factor of late mortality for patients with severe AR undergoing AVR, they always focused on the value of the preoperative LV end-systolic dimension (LVESD) [12, 18 20]. Brown et al. [18] found that larger indexed LV systolic and diastolic dimensions were associated with late mortality for patients with severe AR after surgery treatment. Sambola et al. [11] studied 147 patients (age 52 ± 12 years) who underwent AVR for chronic AR with a mean follow-up of 8 years. A comparison of indexed LVESD 25 mm/m 2 with LVESD 50 mm showed that the use of

5 Y. Wang et al. / Interactive CardioVascular and Thoracic Surgery 429 Figure 4: Kaplan Meier survival curve comparing subgroups: 50% LVEF < 55% group vs LVEF 55% group. LVEF: left ventricular ejection fraction. postoperative mortality was 81 mm. To our knowledge, this may be the first study to evaluate preoperative indicators of prognosis in patients undergoing AVR and so further prospective studies are necessary to confirm our findings. In conclusion, our study shows that AVR can be performed with satisfied outcomes for severe AR in asymptomatic patients with a normal ejection fraction and severe LV dilatation. The best preoperative cut-off values of LVEF and LVEDD to predict postoperative outcomes are 55% and 81 mm, respectively. LVEF < 55% or LVEDD 81 mm are associated with a poorer prognosis of AVR in asymptomatic patients with severe AR accompanied by LVEF 50% and LVEDD > 70 mm. Limitation The present research was a retrospective single-centre observational study and, as such, is subject to limitations. Despite major efforts, as with any observational analysis, unmeasured confounders may influence the accuracy of the reported comparisons. The follow-up was only 94.7% complete, which may result in underreporting of long-term mortality. This study lacked data for late LVEF and LV dimensions. In addition, questionnaire responses may have recall bias that may result in some degree of underestimation. We did not get to collect body surface area or LVESD information for all the patients, and so we failed to analyse the effect of preoperative indexed LVEDD or LVESD on the postoperative outcomes. ORIGINAL ARTICLE ACKNOWLEDGEMENTS We thank Long Yan, Dong Yun and Jiang Weiwei for collecting and recording echocardiographic data. Figure 5: Kaplan Meier survival curve comparing subgroups: 70 mm < LVEDD < 81 mm group vs LVEDD 81 mm group. LVEDD: left ventricular end-diastolic dimension. indexed LVESD improved predictions of poorer prognosis after surgery. Meanwhile, the value of LVESD as an indicator of AV surgery in patients with severe AR is recommended by current guidelines and publications American College of Cardiology/ American Heart Association guidelines present a recommendation of Class IIa that AVR is reasonable for patients with severe AR and LVEF 50% if having LVESD > 50 mm or indexed LVESD > 25 mm/m 2 [3]. Park et al. [21] provided evidence to prove that LVESD ( 45 mm) could be used as an indicator of AV surgery in patients with severe AR and normal LVEF. In the present study, we chose preoperative LVEDD instead of LVESD to reflect preoperative LV dimensions and analysed it as a risk factor of outcomes, because all patients in this cohort had a preoperative LVEDD > 70 mm due to the inclusion criteria of our cohort. We supposed that LVEDD could be more valuable in such a patient population. We indeed found that a larger preoperative LVEDD was a preoperative indicator of poor prognosis in asymptomatic patients with severe AR accompanied by LVEF 50% and LVEDD > 70 mm undergoing AVR, and the best preoperative cut-off value of the LVEDD to predict Funding This work was supported by Key Projects in the National Science & Technology Pillar Program during the Twelfth Five-year Plan Period of China Research of clinical characteristics and surgical treatment of valve disease in China (2011BAI11B19). Conflict of interest: none declared. REFERENCES [1] Klodas E, Sarano ME, Tajik AJ, Mullany CJ, Bailey KR, Seward JB. Aortic regurgitation complicated by extreme left ventricular dilation: long term outcome after surgical correction. J Am Coll Cardiol 1996;27: [2] Taniguchi K, Sawa Y. Contemporary reviews by surgeon: timing of operation for chronic aortic regurgitation. Gen Thorac Cardiovasc Surg 2012; 60: [3] Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP, Guyton RA et al AHA/ACC Guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014;129: [4] Vahanian A, Alfieri O, Andreotti F, Antunes MJ, Barón-Esquivias G, Baumgartner H et al. Guidelines on the management of valvular heart disease (version 2012) The Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur J Cardiothorac Surg 2012;42:S1 44.

6 430 Y. Wang et al. / Interactive CardioVascular and Thoracic Surgery [5] Cohn JN, Ferrari R, Sharpe N. Cardiac remodeling concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. J Am Coll Cardiol 2000;35: [6] Bonow RO, Lakatos E, Maron BJ, Epstein SE. Serial long-term assessment of the natural history of asymptomatic patients with chronic aortic regurgitation and normal left ventricular systolic function. Circulation 1991;84: [7] Turina J, Turina M, Rothlin M, Krayenbuehl HP. Improved late survival in patients with chronic aortic regurgitation by earlier operation. Circulation 1984;70:I [8] Turk R, Varadarajan P, Kamath A, Sampat U, Khandhar S, Patel R et al. Survival benefit of aortic valve replacement in older patients with asymptomatic chronic severe aortic regurgitation. Ann Thorac Surg 2010;89: [9] Chaliki HP, Mohty D, Avierinos JF, Scott CG, Schaff HV, Tajik AJ et al. Outcomes after aortic valve replacement in patients with severe aortic regurgitation and markedly reduced left ventricular function. Circulation 2002;106: [10] Klodas E, Enriquez-Sarano M, Tajik AJ, Mullany CJ, Bailey KR, Seward JB. Aortic regurgitation complicated by extreme left ventricular dilation: long-term outcome after surgical correction. J Am Coll Cardiol 1996;27: [11] Sambola A, Tornos P, Ferreira-Gonzalez I, Evangelista A. Prognostic value of preoperative indexed end-systolic left ventricle diameter in the outcome after surgery in patients with chronic aortic regurgitation. Am Heart J 2008; 155: [12] Nashef SAM, Roques F, Michel P, Gauducheau E, Lemeshow S, Salamon R. European system for cardiac operative risk evaluation (EuroSCORE). Eur J Cardiothorac Surg 1999;16:9 13. [13] O Brien SM, Shahian DM, Filardo G, Ferraris VA, Haan CK, Rich JB et al. The Society of Thoracic Surgeons 2008 cardiac surgery risk models: part 2 isolated valve surgery. Ann Thorac Surg 2009;88:S [14] Scognamiglio R, Negut C, Palisi M, Fasoli G, Dalla-Volta S. Long-term survival and functional results after aortic valve replacement in asymptomatic patients with chronic severe aortic regurgitation and left ventricular dysfunction. J Am Coll Cardiol 2005;45: [15] Bhudia SK, McCarthy PM, Kumpati GS, Helou J, Hoercher KJ, Rajeswaran J et al. Improved outcomes after aortic valve surgery for chronic aortic regurgitation with severe left ventricular dysfunction. J Am Coll Cardiol 2007;49: [16] Rothenburger M, Drebber K, Tjan TD, Schmidt C, Schmid C, Wichter T et al. Aortic valve replacement for aortic regurgitation and stenosis, in patients with severe left ventricular dysfunction. Eur J Cardiothorac Surg 2003;23: [17] Lorell BH, Carabello BA. Left ventricular hypertrophy pathogenesis, detection, and prognosis. Circulation 2000;102: [18] Brown ML, Schaff HV, Suri RM, Li Z, Sundt TM, Dearani JA et al. Indexed left ventricular dimensions best predict survival after aortic valve replacement in patients with aortic valve regurgitation. Ann Thorac Surg 2009;87: [19] Dujardin KS, Enriquez-Sarano M, Schaff HV, Bailey KR, Seward JB, Tajik AJ. Mortality and morbidity of aortic regurgitation in clinical practice a longterm follow-up study. Circulation 1999;99: [20] Cho SH, Byun CS, Kim KW, Chang BC, Yoo KJ, Lee S et al. Preoperative indexed left ventricular dimensions to predict early recovery of left ventricular function after aortic valve replacement for chronic aortic regurgitation. Circ J 2010;74: [21] Park HW, Song JM, Choo SJ, Chung CH, Lee JW, Kim DH et al. Effect of preoperative ejection fraction, left ventricular systolic dimension and hemoglobin level on survival after aortic valve surgery in patients with severe chronic aortic regurgitation. Am J Cardiol 2012;109: ecomment. Why should aortic valve replacement be performed in asymptomatic patients with an enlarged left ventricle but normal left ventricular function? Authors: Thierry Carrel and Lars Englberger Department for Cardiovascular Surgery, University Hospital Bern, Bern, Switzerland doi: /icvts/ivw023 The Author Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. Why should aortic valve replacement be performed in asymptomatic patients with enlarged left ventricle but still normal left ventricular function? The authors have to be congratulated for this paper that clearly demonstrates that careful watching and waiting is not always a good strategy for asymptomatic patients with severe aortic valve regurgitation and a large left ventricular dimension when left ventricular contractility begins to decrease [1]. In patients with severe but chronic aortic regurgitation who remain asymptomatic, the likelihood of adverse events is low as long as the left ventricular function remains normal. However, when the end systolic diameter of the left ventricle (LVESD) is larger than 50 mm, the probability of death and left ventricular (LV) dysfunction has been reported to be as high as 19% per year [2, 3]. Patients with chronic severe AR and who are symptomatic also have a poor long-term prognosis. Once symptoms become apparent, mortality in patients may be as high as 10-20% per year without surgical treatment. Recommendations of the European Society of Cardiology and European Association for Cardio-Thoracic Surgery as well as those of the American College of Cardiology/American Heart Association are still somewhat conservative in this setting and support surgical treatment only in asymptomatic patients with severe AR and impaired LV function (EF <50%) (Class I, Level B) [4]. In patients with LV end diastolic diameter (LVEDD) >70 mm or LVESD >50 mm (or >25 mm/m 2 body surface area in patients with small body size) surgery should be considered (Class IIa, Level C). Justification for this is that the likelihood of irreversible myocardial dysfunction is higher if intervention is delayed. A second justification is that peri- and postoperative results are excellent, if surgery is performed without delay. Furthermore, the guidelines state that good imaging quality and data confirmation with repeated measurements are recommended before surgery in asymptomatic patients. A rapid worsening of ventricular parameters on serial testing is another reason to consider surgery [4]. In that sense, the present study represents a confirmation of the current literature, in which the strongest predictors of operative mortality have been identified as older age, higher preoperative functional class, left ventricular ejection fraction (LVEF) <50%, and LVESD >50 mm. Even though the present analysis originates from a retrospective study, the authors were able to confirm that the cut-off value of LV function is around 50-55% and that of the end diastolic LV diameter is between mm. Particularly younger patients with longer life expectancy would benefit from a more aggressive strategy because once LV pejoration is present, it is always unclear if full reversal of LV dysfunction and recovery from all symptoms will be possible. There are plenty of clinical reports of patients with an impaired LV function doing worse in the early postoperative period after aortic valve replacement - even though it is a straightforward procedure. In that sense, the data from China confirm what has been observed for a long time in surgical departments. There may be different reasons to postpone the surgical replacement: to avoid life-long oral anticoagulation due to implantation of a mechanical prosthesis in younger patients until they reach the age where a tissue valve would be indicated to avoid a surgical procedure at all and wait until a transcatheter aortic valve implantation would be indicated (due to the age or the risk factors of the patient). In fact, in asymptomatic patient with maintained LV function, the aim should be to obtain a mortality rate close to 0-1% and to perform an expedient, less invasive procedure through a ministernotomy (alternatively: a right-lateral small thoracotomy) using a miniaturized cardiopulmonary circuit to reduce the potentially negative effects of extracorporeal circulation. With regard to these aspects, the good results obtained by the Chinese colleagues can still be improved on: clamping times seemed to be rather long for isolated aortic valve repair in the setting of aortic regurgitation (no need for annular debridement) This observation, like previous ones, should urgently promote the realization of a randomized prospective trial to allow for a class IA recommendation, at least for younger patients. Conflict of interest: none declared. References [1] Wang Y, Shi J, Li F, Wang Y, Dong N. Aortic valve replacement for severe aortic regurgitation in asymptomatic patients with normal ejection fraction and severe left ventricular dilatation. Interactive CardioVasc Thorac Surg 2016; 22: [2] Bonow RO, Lakatos E, Maron BJ, Epstein SE. Serial long-term assessment of the natural history of asymptomatic patients with chronic aortic regurgitation and normal left ventricular systolic function. Circulation 1991;84: [3] Dujardin KS, Enriquez-Sarano M, Schaff HV, Bailey KR, Seward JB, Tajik AJ. Mortality and morbidity of aortic regurgitation in clinical practice. A long-term follow-up study. Circulation 1999;99: [4] Vahanian A, Alfieri O, Andreotti F, Antunes MJ, Baron-Esquivias G, Baumgartner H et al. Guidelines on the management of valvular heart disease (version 2012): the Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur J Cardiothorac Surg 2012;42:S1 44.