Reversibility of severe mitral valve regurgitation after left ventricular assist device implantation: single-centre observations from a real-life population of patients

Reversibility of severe mitral valve regurgitation after left ventricular assist device... Abstract OBJECTIVES This study evaluates the impact of untreated preoperative severe mitral valve regurgitation (MR) on outcomes after left ventricular assist device (LVAD) implantation. METHODS Of the 234 patients who received LVAD therapy in our centre during a 6-year period, we selected those who had echocardiographic images of good quality and excluded those who underwent mitral valve replacement prior to or mitral valve repair during LVAD placement. The 128 patients selected were divided into 2 groups: Group A with severe MR (n = 65) and Group B with none to moderate MR (n = 63, 28 with moderate MR). We evaluated transthoracic echocardiography preoperatively [15 (7–28) days before LVAD implantation; median (interquartile range)] and postoperatively up to the last available follow-up [501 (283–848) days after LVAD]. We collected mortality, complications and clinical status indicators of the patient cohort. RESULTS We observed a significant decrease in the severity of MR after LVAD implantation (severe MR 51% pre- vs 6% post-LVAD implantation, P < 0.001). There was no difference between groups in terms of right heart failure, rate of urgent heart transplantation, pump thrombosis or ventricular arrhythmias. There was no difference in 1-year survival and 3-year survival (87.7% vs 88.4% and 71.8% vs 66.6% for Groups A and B, respectively, P = 0.97). CONCLUSIONS Preoperative severe MR resolves in the majority of patients early on after LVAD implantation and is not associated with worse clinical outcomes or intermediate-term survival. Left ventricular assist device, Mitral regurgitation, Tricuspid valve regurgitation INTRODUCTION Currently, left ventricular assist device (LVAD) systems are a treatment option for patients with end-stage heart failure and have been shown to exert a significant clinical benefit, with a survival rate of more than 80% at 1 year and a significant improvement in the quality of life [1]. Functional mitral valve regurgitation (MR) is a common finding in heart failure patients [2]. The pathophysiology can be traced back to the left ventricular dilatation and secondary tethering of the valve leaflets. Therefore, it seems logical that LVADs should improve MR by unloading the left ventricle (LV). Indeed, the international society for heart and lung transplantation (ISHLT) guideline on assist devices does not recommend routine mitral valve (MV) intervention at the time of LVAD implantation in patients with severe MR [3]. Still, prospective studies are not available to guide clinical decisions, and study results can be controversial. MR reversal after LVAD was observed in the majority of studies [4–6], at least at short-term follow-up. A large multicentre study showed no survival disadvantage in patients with severe MR, without intervention on the valve at LVAD implantation [7] but did not evaluate MV reversibility in this context. This study aims to evaluate reversibility of severe MR and observe outcomes in patients with severe MR prior to LVAD implantation. We analysed for the first time echocardiographic follow-up with observations on clinical status, complications and survival over a prolonged follow-up period. MATERIALS AND METHODS At the Leipzig Heart Center, 234 consecutive patients with advanced heart failure underwent LVAD implantation (the HeartWare ventricular assist device, n = 182; the HeartMateII, n = 52) between November 2008 and October 2014. Of these patients, we selected 141 patients who had transthoracic echocardiographic images of good quality before and after LVAD, the exclusion rate being so high due to limited apical windows in LVAD patients. We excluded 11 patients who had undergone MV replacement prior to LVAD implantation and 2 patients with MV reconstruction during LVAD implantation. Of the remaining 128 patients (112 men aged 57 ± 12 years), we analysed transthoracic echocardiography at 6 time points: (i) preoperatively [15 (7–28) days pre-LVAD implantation; median (interquartile range)] (ii) immediately after implantation [16 (9–24) days post-LVAD], (iii) at 1-year follow-up [359 (288–413) days post-LVAD], (iv) at 2-year follow-up [743 (657–821) days post-LVAD], (v) at 3-year follow-up [1105 (1034–1139) days post-LVAD] and (vi) at 4–5-year follow-up [1719 (1565–1933) days post-LVAD]. On the basis of the preoperative severity of MR, we divided our population into 2 groups: patients with severe MR (Group A, n = 65) and patients with less than severe MR (Group B, n = 63). In Group B, 28 had moderate MR and 35 had mild MR. All patients had functional MR. Severe MR was defined according to the present recommendations for quantification of secondary MR (i.e. vena contracta ≥ 7 mm, effective regurgitation orifice area ≥ 20mm2 or regurgitation volume ≥ 30 ml) [8]. The follow-up echocardiographies after LVAD implantation evaluated the left ventricular end-diastolic diameter (LVDD), valve regurgitations, unloading of LV (as a composite of LVDD reduction, MR severity reduction and central position of the interventricular septum), right heart dimension (right ventricular diameter [RVDD] in apical four chamber view [4CV]) and function (tricuspid annular plane systolic excursion [TAPSE] measured in an apical 4CV with M-mode beam positioned on the lateral tricuspid valve annulus), estimated pulmonary artery pressure if tricuspid valve regurgitation (TR) was present [right ventricle (RV) to right atrium (RA) pressure gradient], and evaluation of suction events. At the end of follow-up [501 (283–848) days post-LVAD], we registered clinical status [i.e. New York heart Association (NYHA) class] and adverse outcomes as follows: right heart failure (defined as the need for extracorporeal membrane oxygenation/RVAD implantation or high urgency listing because of right heart failure), hospitalization due to suction events, LVAD thrombosis, ventricular tachycardia, ischemic stroke, bleeding events and death. The six-minute walking test data from 61 patients were available, and the reduced sample size was due to the implementation of this test as a routine only in the last year of the follow-up period. Statistical analysis Echocardiographic data were collected retrospectively and analysed by experienced echocardiographers. The clinical data for each follow-up were gathered from the patients’ records. Continuous variables were expressed as mean ± standard deviation and for non-normal distributions as median and interquartile range. Dichotomous data were presented as percentages. The echocardiographic follow-up data were analysed using statistical methods that are appropriate for the analysis of longitudinal data: for MR and TR severity, linear generalized estimating equations models were used and the remaining parameters were analysed using linear mixed models. For a detailed presentation of the statistical models used, see Supplementary Material, Table S1. To compare survival between groups, we used the Kaplan–Meier curves with the log-rank statistic. Analyses were performed using the SPSS software (IBM-SPSS Statistics, Version 20, IBM Corp.). The study was conducted in accordance with the Declaration of Helsinki and was approved by the local research ethics committee. RESULTS Study population The 2 groups did not differ significantly in terms of patient age, gender, prior valve operations or LVAD device type as listed in Table 1. The majority of the devices used were the HeartWare ventricular assist device. There were significantly more patients with non-ischemic cardiomyopathy in the severe MR group. Table 1: Patient characteristics Total (n = 128) Not severe MR (n = 63) Severe MR (n = 65) P-value Age at implantation, mean ± SD 57 ± 12 57 ± 10 56 ± 13 0.87 Male, n (%) 112 (88) 59 (94) 53 (82) 0.59 Valve surgery, n (%)  Prior MVR 20 (15.6) 11 (17.5) 9 (13.8) 0.63  Prior mitral clip 3 (2.3) 1 (1.6) 2 (3.1) 1  AVR during LVAD 14 (11) 5 (8) 9 (14) 0.34  Prior TVR 7 (5.5) 6 (9.5) 1 (1.5) 0.6 Etiology, n (%)  NICM 66 (52) 25 (38) 41 (62) 0.008  ICM 62 (48) 38 (60) 24 (37) 0.008 LVAD type, n (%)  HVAD 110 (86) 54 (86) 56 (86) 1  The HeartMate II 18 (14) 9 (14) 9 (14) 1 Echocardiography, mean ± SD  LVDD (mm) 73 ± 10 70 ± 8 75 ± 11 0.009  RVDD in 4-chamber view (mm) 46 ± 8 45 ± 9 46 ± 7 0.22  TAPSE (mm) 15 ± 3 14 ± 4 16 ± 4 0.041  RV-RA pressure gradient (mmHg) 36 ± 14 32 ± 14 39 ± 14 0.005  TR≥ 3, n (%) 38 (30) 12 (19) 26 (40) 0.009 Total (n = 128) Not severe MR (n = 63) Severe MR (n = 65) P-value Age at implantation, mean ± SD 57 ± 12 57 ± 10 56 ± 13 0.87 Male, n (%) 112 (88) 59 (94) 53 (82) 0.59 Valve surgery, n (%)  Prior MVR 20 (15.6) 11 (17.5) 9 (13.8) 0.63  Prior mitral clip 3 (2.3) 1 (1.6) 2 (3.1) 1  AVR during LVAD 14 (11) 5 (8) 9 (14) 0.34  Prior TVR 7 (5.5) 6 (9.5) 1 (1.5) 0.6 Etiology, n (%)  NICM 66 (52) 25 (38) 41 (62) 0.008  ICM 62 (48) 38 (60) 24 (37) 0.008 LVAD type, n (%)  HVAD 110 (86) 54 (86) 56 (86) 1  The HeartMate II 18 (14) 9 (14) 9 (14) 1 Echocardiography, mean ± SD  LVDD (mm) 73 ± 10 70 ± 8 75 ± 11 0.009  RVDD in 4-chamber view (mm) 46 ± 8 45 ± 9 46 ± 7 0.22  TAPSE (mm) 15 ± 3 14 ± 4 16 ± 4 0.041  RV-RA pressure gradient (mmHg) 36 ± 14 32 ± 14 39 ± 14 0.005  TR≥ 3, n (%) 38 (30) 12 (19) 26 (40) 0.009 Bold values are statistically significant findings. AVR: aortic valve replacement; HVAD: the HeartWare ventricular assist device; ICM: ischemic cardiomyopathy; LVAD: left ventricular assist device; LVDD: left ventricular end-diastolic diameter; MR: mitral regurgitation; MVR: mitral valve reconstruction; NICM: non-ischemic cardiomyopathy; RA: right atrium; RV; right ventricle; RVDD: right ventricular end-diastolic diameter; SD: standard deviation; TR: tricuspid regurgitation; TVR: tricuspid valve reconstruction; TAPSE: tricuspid annular plane systolic excursion. Table 1: Patient characteristics Total (n = 128) Not severe MR (n = 63) Severe MR (n = 65) P-value Age at implantation, mean ± SD 57 ± 12 57 ± 10 56 ± 13 0.87 Male, n (%) 112 (88) 59 (94) 53 (82) 0.59 Valve surgery, n (%)  Prior MVR 20 (15.6) 11 (17.5) 9 (13.8) 0.63  Prior mitral clip 3 (2.3) 1 (1.6) 2 (3.1) 1  AVR during LVAD 14 (11) 5 (8) 9 (14) 0.34  Prior TVR 7 (5.5) 6 (9.5) 1 (1.5) 0.6 Etiology, n (%)  NICM 66 (52) 25 (38) 41 (62) 0.008  ICM 62 (48) 38 (60) 24 (37) 0.008 LVAD type, n (%)  HVAD 110 (86) 54 (86) 56 (86) 1  The HeartMate II 18 (14) 9 (14) 9 (14) 1 Echocardiography, mean ± SD  LVDD (mm) 73 ± 10 70 ± 8 75 ± 11 0.009  RVDD in 4-chamber view (mm) 46 ± 8 45 ± 9 46 ± 7 0.22  TAPSE (mm) 15 ± 3 14 ± 4 16 ± 4 0.041  RV-RA pressure gradient (mmHg) 36 ± 14 32 ± 14 39 ± 14 0.005  TR≥ 3, n (%) 38 (30) 12 (19) 26 (40) 0.009 Total (n = 128) Not severe MR (n = 63) Severe MR (n = 65) P-value Age at implantation, mean ± SD 57 ± 12 57 ± 10 56 ± 13 0.87 Male, n (%) 112 (88) 59 (94) 53 (82) 0.59 Valve surgery, n (%)  Prior MVR 20 (15.6) 11 (17.5) 9 (13.8) 0.63  Prior mitral clip 3 (2.3) 1 (1.6) 2 (3.1) 1  AVR during LVAD 14 (11) 5 (8) 9 (14) 0.34  Prior TVR 7 (5.5) 6 (9.5) 1 (1.5) 0.6 Etiology, n (%)  NICM 66 (52) 25 (38) 41 (62) 0.008  ICM 62 (48) 38 (60) 24 (37) 0.008 LVAD type, n (%)  HVAD 110 (86) 54 (86) 56 (86) 1  The HeartMate II 18 (14) 9 (14) 9 (14) 1 Echocardiography, mean ± SD  LVDD (mm) 73 ± 10 70 ± 8 75 ± 11 0.009  RVDD in 4-chamber view (mm) 46 ± 8 45 ± 9 46 ± 7 0.22  TAPSE (mm) 15 ± 3 14 ± 4 16 ± 4 0.041  RV-RA pressure gradient (mmHg) 36 ± 14 32 ± 14 39 ± 14 0.005  TR≥ 3, n (%) 38 (30) 12 (19) 26 (40) 0.009 Bold values are statistically significant findings. AVR: aortic valve replacement; HVAD: the HeartWare ventricular assist device; ICM: ischemic cardiomyopathy; LVAD: left ventricular assist device; LVDD: left ventricular end-diastolic diameter; MR: mitral regurgitation; MVR: mitral valve reconstruction; NICM: non-ischemic cardiomyopathy; RA: right atrium; RV; right ventricle; RVDD: right ventricular end-diastolic diameter; SD: standard deviation; TR: tricuspid regurgitation; TVR: tricuspid valve reconstruction; TAPSE: tricuspid annular plane systolic excursion. Before LVAD implantation, patients with severe MR (Group A) were observed to have statistically significant larger LV chambers, higher RV-RA pressure gradients, higher prevalence of severe TR and higher TAPSE values when compared with the patients in Group B. RVDD dimensions did not differ significantly among groups at baseline (Table 1). The echocardiographic features during follow-up are shown in Fig. 1. Figure 1: View largeDownload slide Echocardiographic follow-up depicting the changes in 4 echocardiographic parameters: LVDD, RVDD in apical 4-chamber view, TAPSE, RV to RV pressure gradient during follow-up at 5 time points: PRE, POST, 1Y, 2Y and 3Y. Below each follow-up point, the number of patients with available measurements is depicted. Values are expressed as mean ± 1 SD. P-values denote statistical significance between pre- and immediately post-LVAD values. For all parameters, there was no interaction between groups, suggesting a similar pattern of evolution. Differences between groups are due to baseline values. 1Y: 1-year follow-up; 2Y: 2-year follow-up; 3Y: 3-year follow-up; LVDD: left ventricle end-diastolic diameter; PRE: pre-left ventricle assist device implantation; POST: immediately after LVAD implantation; RA: right atrial; RV: right ventricular; RVDD: right ventricular end-diastolic diameter; SD: standard deviation; TAPSE: tricuspid annular plane systolic excursion. Figure 1: View largeDownload slide Echocardiographic follow-up depicting the changes in 4 echocardiographic parameters: LVDD, RVDD in apical 4-chamber view, TAPSE, RV to RV pressure gradient during follow-up at 5 time points: PRE, POST, 1Y, 2Y and 3Y. Below each follow-up point, the number of patients with available measurements is depicted. Values are expressed as mean ± 1 SD. P-values denote statistical significance between pre- and immediately post-LVAD values. For all parameters, there was no interaction between groups, suggesting a similar pattern of evolution. Differences between groups are due to baseline values. 1Y: 1-year follow-up; 2Y: 2-year follow-up; 3Y: 3-year follow-up; LVDD: left ventricle end-diastolic diameter; PRE: pre-left ventricle assist device implantation; POST: immediately after LVAD implantation; RA: right atrial; RV: right ventricular; RVDD: right ventricular end-diastolic diameter; SD: standard deviation; TAPSE: tricuspid annular plane systolic excursion. The evolution over 5 time points—pre-LVAD, immediately after and at 1-, 2- and 3-year follow-up—was modelled after 4 parameters (LVDD, RVDD, TAPSE and RV-RA pressure gradient) for both groups. The results of the statistical analyses indicate that a statistically significant interaction between time and MR severity could not be detected for any of these parameters (see Supplementary Material and Fig. 1), i.e. there was no evidence that the profiles differed over time in terms of MR severity and that the difference between the 2 groups changed over time. For all parameters, except RVDD, a statistically significant effect of time was observed, with generally a large change at the first time point and without any significant change thereafter. Decrease in LVDD dimension, in both groups, occurred immediately after LVAD implantation, by a mean value of −5.2 mm (95% confidence interval −6.8 to −3.5 mm, P <0.001). The RV-RA pressure gradient decreased significantly immediately after LVAD implantation [−13.2 mmHg (95% confidence interval −17.0; −9.3 mmHg), P < 0.001]. RVDD values did not register a significant change over time, whereas the TAPSE value decreased in both groups [−2.3 mm (95% confidence interval −3.0; −1.7 mm); P < 0.001]. Differences in LVDD, RV-RA pressure gradient and RVDD detected between the groups were due to differences in baseline values. The evolution of MR and TR was modelled for the 5 time points as described earlier and also for the last follow-up available at 4–5 years after LVAD implantation. We observed a significant decrease in the severity of both MR and TR after LVAD implantation (Figs 2 and 3) with a drop in severity immediately after LVAD implantation (P < 0.001) and no significant change over time afterwards. Of the 65 patients with severe MR, only 5 continued to have severe MR at the end of the follow-up. Figure 2: View largeDownload slide MR severity throughout follow-up. The number of patients undergoing echocardiography at each specified follow-up time and for each MR severity grade is depicted inside or above the corresponding bar segment. LVAD: left ventricle assist device; MR: mitral regurgitation. Figure 2: View largeDownload slide MR severity throughout follow-up. The number of patients undergoing echocardiography at each specified follow-up time and for each MR severity grade is depicted inside or above the corresponding bar segment. LVAD: left ventricle assist device; MR: mitral regurgitation. Figure 3: View largeDownload slide TR severity throughout follow-up. The number of patients undergoing echocardiography at each specified follow-up time and for each TR severity grade is depicted inside or above the corresponding bar segment. LVAD: left ventricle assist device; TR: tricuspid regurgitation. Figure 3: View largeDownload slide TR severity throughout follow-up. The number of patients undergoing echocardiography at each specified follow-up time and for each TR severity grade is depicted inside or above the corresponding bar segment. LVAD: left ventricle assist device; TR: tricuspid regurgitation. Only patients with perioperative MR intervention were excluded, and so we observed the same improvement in MR severity in patients with prior MV reconstruction or MitraClip. The same improvement was observed for severe TR, including the 7 patients with prior tricuspid valve reconstruction. Pre-LVAD implantation, Group A demonstrated more patients with severe TR (26 of 65 in Group A and 12 of 63 in Group B, P = 0.009), but this difference was not observed at the end of the follow-up (10 of 65 in Group A and 3 of 63 patients in Group B, P = 0.76). In terms of complications (Table 2) after LVAD implantation, there was no association between the severity of MR and the postoperative rate of right heart failure, pump thrombosis, ventricular arrhythmias, bleeding, ischemic stroke or suction events. Table 2: Complications Total (n = 128) Not severe MR (n = 63) Severe MR (n = 65) P-value Death, n (%) 22 (17) 11 (18) 11 (17) 1 Cardiac death, n (%) 8 (6) 6 (9.5) 2 (3) 0.16 Heart transplantation, n (%) 22 (17) 14 (22) 8 (12) 0.16 ECMO, n (%) 5 (4) 2 (3) 3 (5) 1 RVAD, n (%) 4 (3) 1 (2) 3 (5) 0.62 HU listing for RHF, n (%) 6 (5) 3 (5) 3 (5) 1 ECMO + RVAD + HU, n (%) 11 (9) 5 (8) 6 (9) 1 Suction events, n (%)a 8 (6) 5 (8) 3 (5) 0.49 Pump thrombosis, n (%)a 8 (6) 3 (5) 5 (8) 0.72 VT requiring hospital visit/admission, n (%)a 20 (16) 13 (20) 7 (11) 0.15 Ischemic stroke, n (%)a 1 (0.7) 1 (1.6) 0 0.31 Intracerebral bleeding, n (%)a 3 (2.3) 3 (4.7) 0 0.75 HU listing for GIB, n (%)a 1 (0.7) 0 1 (1.5) 0.32 NYHA Class ≥III, n/n sample (%)  First post-LVAD 68/128 (53) 36/63 (57) 32/65 (49) 0.47  1-year follow-up 50/115 (44) 24/57 (42) 26/58 (45) 0.85 6MWT (m), mean ± SD 365.5 ± 107.2 367.3 ± 112.9 363.6 ± 102.8 0.89  Sample group size, n 61 31 30 Total (n = 128) Not severe MR (n = 63) Severe MR (n = 65) P-value Death, n (%) 22 (17) 11 (18) 11 (17) 1 Cardiac death, n (%) 8 (6) 6 (9.5) 2 (3) 0.16 Heart transplantation, n (%) 22 (17) 14 (22) 8 (12) 0.16 ECMO, n (%) 5 (4) 2 (3) 3 (5) 1 RVAD, n (%) 4 (3) 1 (2) 3 (5) 0.62 HU listing for RHF, n (%) 6 (5) 3 (5) 3 (5) 1 ECMO + RVAD + HU, n (%) 11 (9) 5 (8) 6 (9) 1 Suction events, n (%)a 8 (6) 5 (8) 3 (5) 0.49 Pump thrombosis, n (%)a 8 (6) 3 (5) 5 (8) 0.72 VT requiring hospital visit/admission, n (%)a 20 (16) 13 (20) 7 (11) 0.15 Ischemic stroke, n (%)a 1 (0.7) 1 (1.6) 0 0.31 Intracerebral bleeding, n (%)a 3 (2.3) 3 (4.7) 0 0.75 HU listing for GIB, n (%)a 1 (0.7) 0 1 (1.5) 0.32 NYHA Class ≥III, n/n sample (%)  First post-LVAD 68/128 (53) 36/63 (57) 32/65 (49) 0.47  1-year follow-up 50/115 (44) 24/57 (42) 26/58 (45) 0.85 6MWT (m), mean ± SD 365.5 ± 107.2 367.3 ± 112.9 363.6 ± 102.8 0.89  Sample group size, n 61 31 30 a The number of patients who had the specific complication (irrespective of how many episodes of the complication in each patient). ECMO: extracorporeal membrane oxygenation; GIB: gastrointestinal bleeding; HU-listing: high urgency listing; LVAD: left ventricular assist device; 6MWT: six minutes walking test; MR: mitral regurgitation; NYHA: New York Heart Association; RHF: right heart failure; RVAD: right ventricular assist device; SD: standard deviation; VT: ventricular tachycardia. Table 2: Complications Total (n = 128) Not severe MR (n = 63) Severe MR (n = 65) P-value Death, n (%) 22 (17) 11 (18) 11 (17) 1 Cardiac death, n (%) 8 (6) 6 (9.5) 2 (3) 0.16 Heart transplantation, n (%) 22 (17) 14 (22) 8 (12) 0.16 ECMO, n (%) 5 (4) 2 (3) 3 (5) 1 RVAD, n (%) 4 (3) 1 (2) 3 (5) 0.62 HU listing for RHF, n (%) 6 (5) 3 (5) 3 (5) 1 ECMO + RVAD + HU, n (%) 11 (9) 5 (8) 6 (9) 1 Suction events, n (%)a 8 (6) 5 (8) 3 (5) 0.49 Pump thrombosis, n (%)a 8 (6) 3 (5) 5 (8) 0.72 VT requiring hospital visit/admission, n (%)a 20 (16) 13 (20) 7 (11) 0.15 Ischemic stroke, n (%)a 1 (0.7) 1 (1.6) 0 0.31 Intracerebral bleeding, n (%)a 3 (2.3) 3 (4.7) 0 0.75 HU listing for GIB, n (%)a 1 (0.7) 0 1 (1.5) 0.32 NYHA Class ≥III, n/n sample (%)  First post-LVAD 68/128 (53) 36/63 (57) 32/65 (49) 0.47  1-year follow-up 50/115 (44) 24/57 (42) 26/58 (45) 0.85 6MWT (m), mean ± SD 365.5 ± 107.2 367.3 ± 112.9 363.6 ± 102.8 0.89  Sample group size, n 61 31 30 Total (n = 128) Not severe MR (n = 63) Severe MR (n = 65) P-value Death, n (%) 22 (17) 11 (18) 11 (17) 1 Cardiac death, n (%) 8 (6) 6 (9.5) 2 (3) 0.16 Heart transplantation, n (%) 22 (17) 14 (22) 8 (12) 0.16 ECMO, n (%) 5 (4) 2 (3) 3 (5) 1 RVAD, n (%) 4 (3) 1 (2) 3 (5) 0.62 HU listing for RHF, n (%) 6 (5) 3 (5) 3 (5) 1 ECMO + RVAD + HU, n (%) 11 (9) 5 (8) 6 (9) 1 Suction events, n (%)a 8 (6) 5 (8) 3 (5) 0.49 Pump thrombosis, n (%)a 8 (6) 3 (5) 5 (8) 0.72 VT requiring hospital visit/admission, n (%)a 20 (16) 13 (20) 7 (11) 0.15 Ischemic stroke, n (%)a 1 (0.7) 1 (1.6) 0 0.31 Intracerebral bleeding, n (%)a 3 (2.3) 3 (4.7) 0 0.75 HU listing for GIB, n (%)a 1 (0.7) 0 1 (1.5) 0.32 NYHA Class ≥III, n/n sample (%)  First post-LVAD 68/128 (53) 36/63 (57) 32/65 (49) 0.47  1-year follow-up 50/115 (44) 24/57 (42) 26/58 (45) 0.85 6MWT (m), mean ± SD 365.5 ± 107.2 367.3 ± 112.9 363.6 ± 102.8 0.89  Sample group size, n 61 31 30 a The number of patients who had the specific complication (irrespective of how many episodes of the complication in each patient). ECMO: extracorporeal membrane oxygenation; GIB: gastrointestinal bleeding; HU-listing: high urgency listing; LVAD: left ventricular assist device; 6MWT: six minutes walking test; MR: mitral regurgitation; NYHA: New York Heart Association; RHF: right heart failure; RVAD: right ventricular assist device; SD: standard deviation; VT: ventricular tachycardia. There was also no difference in the occurrence of clinically significant aortic valve insufficiency or closed aortic valve. Patients in both groups had a similar clinical status, which was assessed using the six-minute walking test and the NYHA class. During follow-up, 8 patients demonstrated severe MR, of whom 5 patients had persistent preoperative severe MR and 3 patients developed de novo severe MR. The presence of severe MR at the final follow-up was associated with poor unloading of the LV and with higher rate of hospital admissions [1 (0.25–2.75) vs 0 (0–1) per year P = 0.016]. The main reason for hospital admission in those patients with severe MR at the end of the follow-up was ventricular tachycardia. At the time of the final assessment, no difference was observed in survival between groups (Fig. 4). Figure 4: View largeDownload slide The Kaplan–Meier survival curves in patients with and without severe MR pre-LVAD implantation (the log-rank Mantel Cox P-value = 0.974). LVAD: left ventricle assist device; MR: mitral regurgitation. Figure 4: View largeDownload slide The Kaplan–Meier survival curves in patients with and without severe MR pre-LVAD implantation (the log-rank Mantel Cox P-value = 0.974). LVAD: left ventricle assist device; MR: mitral regurgitation. DISCUSSION Mitral regurgitation The reversibility of MR after LVAD implantation has already been well described [3–6]. Nevertheless, apart from verifying these findings in our study population, we analysed for the first time the clinical association between preoperative severe MR in patients undergoing LVAD implantation and haemodynamic changes affecting pulmonary circulation, right heart function and outcomes over a prolonged follow-up period. MR is a common finding in patients with heart failure, and it correlates with the severity of the disease [9]. Accordingly, we observed greater LV end-diastolic diameters in the severe MR group, suggesting a more advanced stage of remodelling of the left heart, leading to annular dilatation and consecutive loss of coaptation of the valve leaflets. Despite a more advanced state of heart failure, this LV remodelling seems to be reversible in a large majority of LVAD patients. In our study population, we observed that LVDD decreased immediately after LVAD implantation in both groups to a similar degree and that the LVDD remained higher in the severe MR group during follow-up. The significant decrease in LVDD, MR severity and subsequent RV-RA gradient occurred predominantly within the time interval from implantation to the first echocardiographic follow-up. This effect was maintained at 1 year and until the 3 years follow-up, but without further significant change as observed within the first postoperative period. The device-specific pump speed was similar between groups. These observations demonstrate the ability of the LVAD to unload the LV irrespective of the initial LV dimension or MR severity. The unloading of the LV improves the mitral insufficiency in the severe MR group and provides the same outcomes when compared with the non-severe MR group. This also suggests that MR reversal is a good marker of efficient LV unloading. Both groups included a similar number of patients who underwent MV repair and the MitraClip prior to LVAD implantation. The same improvement of MR severity was observed both in this subgroup and in patients with native valve anatomy, suggesting a benefit of LVAD therapy in this patient category as well. Of the 65 patients with severe MR, only 5 patients continued to have severe MR at the last follow-up, and at the end of the follow-up, only 3 additional patients progressed to severe MR (1 patient from Group A, who initially improved and 2 patients from Group B). The 8 patients with severe MR at their last outpatient visit had poor LV unloading and more hospital readmissions due to cardiovascular causes, suggesting a reduced benefit from LVAD therapy. This was only an observation. No relevant conclusion can be drawn from such a small patient number, but a recent study by Kassis et al. [10] showed the association between persistent severe MR and adverse outcomes in LVAD patients. Kitada et al. [11] suggested that posterior displacement of MV leaflets predicted persistent MR 1 week after LVAD implantation, without affecting major adverse outcomes at 1-year follow-up; however, long-term follow-up data are still missing. Further prospective and large population studies are needed to assess this issue. The pattern of MR reversal demonstrated in our patient cohort suggests that the presence of persistent severe MR detected at the early post-LVAD echocardiographic study should trigger research on additional therapy strategies, knowing that the degree of MR will not improve on its own and could increase the likelihood of adverse outcomes of this subgroup of patients. To date, conflicting evidence from retrospective studies still creates controversy about the surgical treatment of MR at the time of LVAD implantation. A multicentric study by Stulak et al. [7] comparing outcomes in patients with preoperative moderate to severe MR with those with mild MR pleaded in favour of no valve intervention. In contrast, a recent monocentric comparison study of Tanaka et al. [12] showed that the preoperative moderate to severe MR group with ‘spontaneous’ correction after LVAD implantation still had worse outcomes at 1-year follow-up (i.e. survival and freedom of MR) when compared with the group with concomitant ‘surgical’ correction of the MR, but no difference in hospital admissions was noted, and clinical status was not assessed. Furthermore, we can speculate, in the light of recent observations about LV recovery in LVAD patients, that only at the time of LVAD explantation MV repair should be considered. This issue further stresses the importance of future multicentre prospective studies addressing predictors of persistent MR and comparing outcomes with different approaches for a refined and adequate individual decision-making process for LVAD candidates. Right ventricular function and failure RV failure is one of the most feared complications after LVAD implantation [13, 14]. There is no conclusive evidence regarding predictors of post-LVAD RV failure implantation or selection of those who would benefit from elective biventricular assist device implantation. The current definition of right heart failure (RHF) is based mainly on haemodynamic and therapeutic criteria, not on echocardiographic parameters [15]; however, a prospective study analysing echocardiographic parameters prior to and after LVAD implantation is in progress [16]. In our study population, there was no difference between groups in terms of late RHF defined as the necessity of RVAD or extracorporeal membrane oxygenation implantation, or listing for heart transplantation due to RHF. This may suggest that severe MR is not necessarily associated with advanced RV dysfunction due to increased afterload in the long-term follow-up but rather a reversible mechanism with a good chance of regression after LVAD implantation. As noted above, there were no differences in pump speed and LVDD reduction between groups suggesting that there is no additional preload for the RV after LVAD implantation in patients with preoperative severe MR. Indeed, as shown in the retrospective studies, RV function improved in the majority of LVAD patients [17, 18]. The unloading of the LV decreased pulmonary pressure [19], and thus, the additional preload due to increased venous return could still be managed by the RV. New data has suggested that even though RV afterload reduction occurred after LVAD implantation, the RV did not immediately adapt to the increased preload after implantation; rather, it adapts progressively over time [20]. We evaluated right heart function by measuring TAPSE, RVDD and TR grade. In our population, we noticed a significant decrease in TAPSE in all patients after LVAD implantation, which did not change significantly afterwards. To our knowledge, only 1 study showed an improvement in TAPSE values after LVAD implantation [17], whereas another study described a reduction in TAPSE [21]. Two studies showed that TAPSE was not reliable after cardiac surgery: TAPSE was decreased after cardiothomy, without a reduction in the RV function measured using 3D echo or deformation imaging [22, 23]. Moreover, the decrease in TAPSE was a result of a change in the RV and LV interdependence after LVAD implantation with fixation of the LV to the inflow cannula. Therefore, semiquantitative or quantitative RV function assessment, or a combination of TAPSE, TR severity and RV dimensions was recommended [18, 24]. On the other hand, although TAPSE decreased in all patients, we noticed significantly lower values in patients who developed RHF at a later stage (10.73 ± 2.9 vs 13.15 ± 2.6 mm, P <0.001). This suggests that an absolute value of TAPSE after LVAD implantation could still be used to identify patients at risk of RHF. In our study, the small number of patients with severe RHF (n = 8) did not allow us to determine a new cut-off regarding TAPSE value as a predictor of severe RV dysfunction. Some studies imply that TAPSE may decrease when the RV does not have to pump against a high afterload and that it is a predictor of RV dysfunction only if it is associated with persistent significant TR [25, 21]. In our study population, TR severity decreased significantly without any intervention on the valve. Although TAPSE decreased in the whole population, there were only a small number of patients with persistent severe TR (Fig. 3). This suggests that the assessment of TR severity in combination with TAPSE after LVAD is a better marker of RV function and may also be a better predictor of late adverse outcomes, which should be evaluated in a larger cohort of patients. Left ventricular assist device and tricuspid regurgitation The current indication of the ISHLT guideline is to consider tricuspid valve repair if the patient presents with moderate to severe TR before LVAD implantation [2]. Small studies have shown a trend toward improved survival and improved early clinical outcomes such as length of inotropic infusion, renal insufficiency post-LVAD and length of hospital stay after tricuspid valve repair during LVAD insertion [26–29]. However, a meta-analysis of these studies did not show a difference in early outcomes, renal failure or necessity of RVAD implantation [30]. The majority of studies favour tricuspid valve repair because it was not associated with significant increase in operative risk. Because of our patient selection, we cannot comment on the early RV failure incidence in patients with severe TR, but we did notice a definite improvement in TR at the first echocardiography, which was maintained throughout the follow-up (Fig. 3). We also observed that Group A developed significantly more severe TR before LVAD implantation. This difference disappeared at the last follow-up. This may suggest that the 2 pathologies were linked as they improved synergistically after LVAD implantation. Although patients with severe MR and TR may be considered to be in a more advanced phase of the disease, our findings suggest that LVADs have a good therapeutic potential in these patients. Mortality and outcomes after left ventricular assist device The overall survival of patients in our cohort seems to be better when compared with results from interagency registry for mechanically assisted circulatory support (INTERMACS) reports (69% vs 59% at 3 years) [1] because we selected patients with available pre- and post-LVAD echocardiography and thus have excluded those who died in the immediate postoperative period. Although in our study there was no statistically significant difference in intermediate survival between patients with severe and less than severe MR before LVAD implantation [1- and 3-year survival (87.7% vs 88.4% and 71.8% vs 66.6%) for Groups A and B, respectively, Fig. 4], a recent multicentre study showed even improved survival in patients with significant MR [7]. Limitations The retrospective nature with all its inherent limitations is a major limitation of this study. In our attempt to understand haemodynamic changes, we selected patients with good echocardiographic windows, thus introducing a bias especially with regard to patients who died early and did not have an echocardiographic study after LVAD implantation. We excluded the 4–5-year follow-up in the evaluation of LVDD, RVDD, RV-RA pressure gradient and TAPSE because of few available data at this time point. CONCLUSIONS Preoperative severe MR substantially decreases shortly after LVAD implantation in majority of the patients and is associated with unloading of the LV and decreased pulmonary pressure. This early effect is sustained during an intermediate follow-up period, suggesting that improvement in MR should be observed at the first postoperative echocardiographic study. Additionally, patients with severe MR pre-LVAD had similar functional status, complication rates and survival as patients with non-severe MR prior to LVAD implantation. SUPPLEMENTARY MATERIAL Supplementary material is available at EJCTS online. ACKNOWLEDGEMENTS The authors are grateful to Monica Mattes for the English language revision. Conflict of interest: none declared. REFERENCES 1 Kirklin JK , Naftel DC , Pagani FD , Kormos RL , Stevenson LW , Blume ED et al. Seventh INTERMACS annual report: 15,000 patients and counting . J Heart Lung Transplant 2015 ; 34 : 1495 – 504 . Google Scholar CrossRef Search ADS PubMed 2 Ciarka A , Van de Veire N Secondary mitral regurgitation: pathophysiology, diagnosis, and treatment . Heart 2011 ; 97 : 1012 – 23 . Google Scholar CrossRef Search ADS PubMed 3 Feldman D , Pamboukian SV , Teuteberg JJ , Birks E , Lietz K , Moore SA et al. The 2013 International Society for Heart and Lung Transplantation Guidelines for mechanical circulatory support: executive summary . J Heart Lung Transplant 2013 ; 32 : 157 – 87 . 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Is right ventricular systolic function reduced after cardiac surgery? A two- and three-dimensional echocardiographic study . Eur J Echocardiogr 2009 ; 10 : 630 – 4 . Google Scholar CrossRef Search ADS PubMed 24 Kukucka M , Potapov E , Stepanenko A , Weller K , Mladenow A , Kuppe H et al. Acute impact of left ventricular unloading by left ventricular assist device on the right ventricle geometry and function: effect of nitric oxide inhalation . J Thorac Cardiovasc Surg 2011 ; 141 : 1009 – 14 . Google Scholar CrossRef Search ADS PubMed 25 Lee S , Kamdar F , Madlon-Kay R , Boyle A , Colvin-Adams M , Pritzker M et al. Effects of the HeartMate II continuous-flow left ventricular assist device on right ventricular function . J Heart Lung Transplant 2010 ; 29 : 209 – 15 . Google Scholar CrossRef Search ADS PubMed 26 Piacentino V 3rd , Williams ML , Depp T , Garcia-Huerta K , Blue L , Lodge AJ et al. Impact of tricuspid valve regurgitation in patients treated with implantable left ventricular assist devices . Ann Thorac Surg 2011 ; 91 : 1342 – 6 ; discussion 1346–7. Google Scholar CrossRef Search ADS PubMed 27 Piacentino V 3rd , Troupes CD , Ganapathi AM , Blue LJ , Mackensen GB , Swaminathan M et al. Clinical impact of concomitant tricuspid valve procedures during left ventricular assist device implantation . Ann Thorac Surg 2011 ; 92 : 1414 – 8 ; discussion 1418–9 Google Scholar CrossRef Search ADS PubMed 28 Saeed D , Kidambi T , Shalli S , Lapin B , Malaisrie SC , Lee R et al. Tricuspid valve repair with left ventricular assist device implantation: is it warranted? J Heart Lung Transplant 2011 ; 30 : 530 – 5 . Google Scholar CrossRef Search ADS PubMed 29 Piacentino V 3rd , Ganapathi AM , Stafford-Smith M , Hsieh MK , Patel CB , Simeone AA et al. Utility of concomitant tricuspid valve procedures for patients undergoing implantation of a continuous-flow left ventricular device . J Thorac Cardiovasc Surg 2012 ; 144 : 1217 – 21 . Google Scholar CrossRef Search ADS PubMed 30 Dunlay SM , Deo SV , Park SJ. Impact of tricuspid valve surgery at the time of left ventricular assist device insertion on postoperative outcomes . ASAIO J 2015 ; 61 : 15 – 20 . Google Scholar CrossRef Search ADS PubMed © The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Cardio-Thoracic Surgery Oxford University Press

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Abstract

Abstract OBJECTIVES This study evaluates the impact of untreated preoperative severe mitral valve regurgitation (MR) on outcomes after left ventricular assist device (LVAD) implantation. METHODS Of the 234 patients who received LVAD therapy in our centre during a 6-year period, we selected those who had echocardiographic images of good quality and excluded those who underwent mitral valve replacement prior to or mitral valve repair during LVAD placement. The 128 patients selected were divided into 2 groups: Group A with severe MR (n = 65) and Group B with none to moderate MR (n = 63, 28 with moderate MR). We evaluated transthoracic echocardiography preoperatively [15 (7–28) days before LVAD implantation; median (interquartile range)] and postoperatively up to the last available follow-up [501 (283–848) days after LVAD]. We collected mortality, complications and clinical status indicators of the patient cohort. RESULTS We observed a significant decrease in the severity of MR after LVAD implantation (severe MR 51% pre- vs 6% post-LVAD implantation, P < 0.001). There was no difference between groups in terms of right heart failure, rate of urgent heart transplantation, pump thrombosis or ventricular arrhythmias. There was no difference in 1-year survival and 3-year survival (87.7% vs 88.4% and 71.8% vs 66.6% for Groups A and B, respectively, P = 0.97). CONCLUSIONS Preoperative severe MR resolves in the majority of patients early on after LVAD implantation and is not associated with worse clinical outcomes or intermediate-term survival. Left ventricular assist device, Mitral regurgitation, Tricuspid valve regurgitation INTRODUCTION Currently, left ventricular assist device (LVAD) systems are a treatment option for patients with end-stage heart failure and have been shown to exert a significant clinical benefit, with a survival rate of more than 80% at 1 year and a significant improvement in the quality of life [1]. Functional mitral valve regurgitation (MR) is a common finding in heart failure patients [2]. The pathophysiology can be traced back to the left ventricular dilatation and secondary tethering of the valve leaflets. Therefore, it seems logical that LVADs should improve MR by unloading the left ventricle (LV). Indeed, the international society for heart and lung transplantation (ISHLT) guideline on assist devices does not recommend routine mitral valve (MV) intervention at the time of LVAD implantation in patients with severe MR [3]. Still, prospective studies are not available to guide clinical decisions, and study results can be controversial. MR reversal after LVAD was observed in the majority of studies [4–6], at least at short-term follow-up. A large multicentre study showed no survival disadvantage in patients with severe MR, without intervention on the valve at LVAD implantation [7] but did not evaluate MV reversibility in this context. This study aims to evaluate reversibility of severe MR and observe outcomes in patients with severe MR prior to LVAD implantation. We analysed for the first time echocardiographic follow-up with observations on clinical status, complications and survival over a prolonged follow-up period. MATERIALS AND METHODS At the Leipzig Heart Center, 234 consecutive patients with advanced heart failure underwent LVAD implantation (the HeartWare ventricular assist device, n = 182; the HeartMateII, n = 52) between November 2008 and October 2014. Of these patients, we selected 141 patients who had transthoracic echocardiographic images of good quality before and after LVAD, the exclusion rate being so high due to limited apical windows in LVAD patients. We excluded 11 patients who had undergone MV replacement prior to LVAD implantation and 2 patients with MV reconstruction during LVAD implantation. Of the remaining 128 patients (112 men aged 57 ± 12 years), we analysed transthoracic echocardiography at 6 time points: (i) preoperatively [15 (7–28) days pre-LVAD implantation; median (interquartile range)] (ii) immediately after implantation [16 (9–24) days post-LVAD], (iii) at 1-year follow-up [359 (288–413) days post-LVAD], (iv) at 2-year follow-up [743 (657–821) days post-LVAD], (v) at 3-year follow-up [1105 (1034–1139) days post-LVAD] and (vi) at 4–5-year follow-up [1719 (1565–1933) days post-LVAD]. On the basis of the preoperative severity of MR, we divided our population into 2 groups: patients with severe MR (Group A, n = 65) and patients with less than severe MR (Group B, n = 63). In Group B, 28 had moderate MR and 35 had mild MR. All patients had functional MR. Severe MR was defined according to the present recommendations for quantification of secondary MR (i.e. vena contracta ≥ 7 mm, effective regurgitation orifice area ≥ 20mm2 or regurgitation volume ≥ 30 ml) [8]. The follow-up echocardiographies after LVAD implantation evaluated the left ventricular end-diastolic diameter (LVDD), valve regurgitations, unloading of LV (as a composite of LVDD reduction, MR severity reduction and central position of the interventricular septum), right heart dimension (right ventricular diameter [RVDD] in apical four chamber view [4CV]) and function (tricuspid annular plane systolic excursion [TAPSE] measured in an apical 4CV with M-mode beam positioned on the lateral tricuspid valve annulus), estimated pulmonary artery pressure if tricuspid valve regurgitation (TR) was present [right ventricle (RV) to right atrium (RA) pressure gradient], and evaluation of suction events. At the end of follow-up [501 (283–848) days post-LVAD], we registered clinical status [i.e. New York heart Association (NYHA) class] and adverse outcomes as follows: right heart failure (defined as the need for extracorporeal membrane oxygenation/RVAD implantation or high urgency listing because of right heart failure), hospitalization due to suction events, LVAD thrombosis, ventricular tachycardia, ischemic stroke, bleeding events and death. The six-minute walking test data from 61 patients were available, and the reduced sample size was due to the implementation of this test as a routine only in the last year of the follow-up period. Statistical analysis Echocardiographic data were collected retrospectively and analysed by experienced echocardiographers. The clinical data for each follow-up were gathered from the patients’ records. Continuous variables were expressed as mean ± standard deviation and for non-normal distributions as median and interquartile range. Dichotomous data were presented as percentages. The echocardiographic follow-up data were analysed using statistical methods that are appropriate for the analysis of longitudinal data: for MR and TR severity, linear generalized estimating equations models were used and the remaining parameters were analysed using linear mixed models. For a detailed presentation of the statistical models used, see Supplementary Material, Table S1. To compare survival between groups, we used the Kaplan–Meier curves with the log-rank statistic. Analyses were performed using the SPSS software (IBM-SPSS Statistics, Version 20, IBM Corp.). The study was conducted in accordance with the Declaration of Helsinki and was approved by the local research ethics committee. RESULTS Study population The 2 groups did not differ significantly in terms of patient age, gender, prior valve operations or LVAD device type as listed in Table 1. The majority of the devices used were the HeartWare ventricular assist device. There were significantly more patients with non-ischemic cardiomyopathy in the severe MR group. Table 1: Patient characteristics Total (n = 128) Not severe MR (n = 63) Severe MR (n = 65) P-value Age at implantation, mean ± SD 57 ± 12 57 ± 10 56 ± 13 0.87 Male, n (%) 112 (88) 59 (94) 53 (82) 0.59 Valve surgery, n (%)  Prior MVR 20 (15.6) 11 (17.5) 9 (13.8) 0.63  Prior mitral clip 3 (2.3) 1 (1.6) 2 (3.1) 1  AVR during LVAD 14 (11) 5 (8) 9 (14) 0.34  Prior TVR 7 (5.5) 6 (9.5) 1 (1.5) 0.6 Etiology, n (%)  NICM 66 (52) 25 (38) 41 (62) 0.008  ICM 62 (48) 38 (60) 24 (37) 0.008 LVAD type, n (%)  HVAD 110 (86) 54 (86) 56 (86) 1  The HeartMate II 18 (14) 9 (14) 9 (14) 1 Echocardiography, mean ± SD  LVDD (mm) 73 ± 10 70 ± 8 75 ± 11 0.009  RVDD in 4-chamber view (mm) 46 ± 8 45 ± 9 46 ± 7 0.22  TAPSE (mm) 15 ± 3 14 ± 4 16 ± 4 0.041  RV-RA pressure gradient (mmHg) 36 ± 14 32 ± 14 39 ± 14 0.005  TR≥ 3, n (%) 38 (30) 12 (19) 26 (40) 0.009 Total (n = 128) Not severe MR (n = 63) Severe MR (n = 65) P-value Age at implantation, mean ± SD 57 ± 12 57 ± 10 56 ± 13 0.87 Male, n (%) 112 (88) 59 (94) 53 (82) 0.59 Valve surgery, n (%)  Prior MVR 20 (15.6) 11 (17.5) 9 (13.8) 0.63  Prior mitral clip 3 (2.3) 1 (1.6) 2 (3.1) 1  AVR during LVAD 14 (11) 5 (8) 9 (14) 0.34  Prior TVR 7 (5.5) 6 (9.5) 1 (1.5) 0.6 Etiology, n (%)  NICM 66 (52) 25 (38) 41 (62) 0.008  ICM 62 (48) 38 (60) 24 (37) 0.008 LVAD type, n (%)  HVAD 110 (86) 54 (86) 56 (86) 1  The HeartMate II 18 (14) 9 (14) 9 (14) 1 Echocardiography, mean ± SD  LVDD (mm) 73 ± 10 70 ± 8 75 ± 11 0.009  RVDD in 4-chamber view (mm) 46 ± 8 45 ± 9 46 ± 7 0.22  TAPSE (mm) 15 ± 3 14 ± 4 16 ± 4 0.041  RV-RA pressure gradient (mmHg) 36 ± 14 32 ± 14 39 ± 14 0.005  TR≥ 3, n (%) 38 (30) 12 (19) 26 (40) 0.009 Bold values are statistically significant findings. AVR: aortic valve replacement; HVAD: the HeartWare ventricular assist device; ICM: ischemic cardiomyopathy; LVAD: left ventricular assist device; LVDD: left ventricular end-diastolic diameter; MR: mitral regurgitation; MVR: mitral valve reconstruction; NICM: non-ischemic cardiomyopathy; RA: right atrium; RV; right ventricle; RVDD: right ventricular end-diastolic diameter; SD: standard deviation; TR: tricuspid regurgitation; TVR: tricuspid valve reconstruction; TAPSE: tricuspid annular plane systolic excursion. Table 1: Patient characteristics Total (n = 128) Not severe MR (n = 63) Severe MR (n = 65) P-value Age at implantation, mean ± SD 57 ± 12 57 ± 10 56 ± 13 0.87 Male, n (%) 112 (88) 59 (94) 53 (82) 0.59 Valve surgery, n (%)  Prior MVR 20 (15.6) 11 (17.5) 9 (13.8) 0.63  Prior mitral clip 3 (2.3) 1 (1.6) 2 (3.1) 1  AVR during LVAD 14 (11) 5 (8) 9 (14) 0.34  Prior TVR 7 (5.5) 6 (9.5) 1 (1.5) 0.6 Etiology, n (%)  NICM 66 (52) 25 (38) 41 (62) 0.008  ICM 62 (48) 38 (60) 24 (37) 0.008 LVAD type, n (%)  HVAD 110 (86) 54 (86) 56 (86) 1  The HeartMate II 18 (14) 9 (14) 9 (14) 1 Echocardiography, mean ± SD  LVDD (mm) 73 ± 10 70 ± 8 75 ± 11 0.009  RVDD in 4-chamber view (mm) 46 ± 8 45 ± 9 46 ± 7 0.22  TAPSE (mm) 15 ± 3 14 ± 4 16 ± 4 0.041  RV-RA pressure gradient (mmHg) 36 ± 14 32 ± 14 39 ± 14 0.005  TR≥ 3, n (%) 38 (30) 12 (19) 26 (40) 0.009 Total (n = 128) Not severe MR (n = 63) Severe MR (n = 65) P-value Age at implantation, mean ± SD 57 ± 12 57 ± 10 56 ± 13 0.87 Male, n (%) 112 (88) 59 (94) 53 (82) 0.59 Valve surgery, n (%)  Prior MVR 20 (15.6) 11 (17.5) 9 (13.8) 0.63  Prior mitral clip 3 (2.3) 1 (1.6) 2 (3.1) 1  AVR during LVAD 14 (11) 5 (8) 9 (14) 0.34  Prior TVR 7 (5.5) 6 (9.5) 1 (1.5) 0.6 Etiology, n (%)  NICM 66 (52) 25 (38) 41 (62) 0.008  ICM 62 (48) 38 (60) 24 (37) 0.008 LVAD type, n (%)  HVAD 110 (86) 54 (86) 56 (86) 1  The HeartMate II 18 (14) 9 (14) 9 (14) 1 Echocardiography, mean ± SD  LVDD (mm) 73 ± 10 70 ± 8 75 ± 11 0.009  RVDD in 4-chamber view (mm) 46 ± 8 45 ± 9 46 ± 7 0.22  TAPSE (mm) 15 ± 3 14 ± 4 16 ± 4 0.041  RV-RA pressure gradient (mmHg) 36 ± 14 32 ± 14 39 ± 14 0.005  TR≥ 3, n (%) 38 (30) 12 (19) 26 (40) 0.009 Bold values are statistically significant findings. AVR: aortic valve replacement; HVAD: the HeartWare ventricular assist device; ICM: ischemic cardiomyopathy; LVAD: left ventricular assist device; LVDD: left ventricular end-diastolic diameter; MR: mitral regurgitation; MVR: mitral valve reconstruction; NICM: non-ischemic cardiomyopathy; RA: right atrium; RV; right ventricle; RVDD: right ventricular end-diastolic diameter; SD: standard deviation; TR: tricuspid regurgitation; TVR: tricuspid valve reconstruction; TAPSE: tricuspid annular plane systolic excursion. Before LVAD implantation, patients with severe MR (Group A) were observed to have statistically significant larger LV chambers, higher RV-RA pressure gradients, higher prevalence of severe TR and higher TAPSE values when compared with the patients in Group B. RVDD dimensions did not differ significantly among groups at baseline (Table 1). The echocardiographic features during follow-up are shown in Fig. 1. Figure 1: View largeDownload slide Echocardiographic follow-up depicting the changes in 4 echocardiographic parameters: LVDD, RVDD in apical 4-chamber view, TAPSE, RV to RV pressure gradient during follow-up at 5 time points: PRE, POST, 1Y, 2Y and 3Y. Below each follow-up point, the number of patients with available measurements is depicted. Values are expressed as mean ± 1 SD. P-values denote statistical significance between pre- and immediately post-LVAD values. For all parameters, there was no interaction between groups, suggesting a similar pattern of evolution. Differences between groups are due to baseline values. 1Y: 1-year follow-up; 2Y: 2-year follow-up; 3Y: 3-year follow-up; LVDD: left ventricle end-diastolic diameter; PRE: pre-left ventricle assist device implantation; POST: immediately after LVAD implantation; RA: right atrial; RV: right ventricular; RVDD: right ventricular end-diastolic diameter; SD: standard deviation; TAPSE: tricuspid annular plane systolic excursion. Figure 1: View largeDownload slide Echocardiographic follow-up depicting the changes in 4 echocardiographic parameters: LVDD, RVDD in apical 4-chamber view, TAPSE, RV to RV pressure gradient during follow-up at 5 time points: PRE, POST, 1Y, 2Y and 3Y. Below each follow-up point, the number of patients with available measurements is depicted. Values are expressed as mean ± 1 SD. P-values denote statistical significance between pre- and immediately post-LVAD values. For all parameters, there was no interaction between groups, suggesting a similar pattern of evolution. Differences between groups are due to baseline values. 1Y: 1-year follow-up; 2Y: 2-year follow-up; 3Y: 3-year follow-up; LVDD: left ventricle end-diastolic diameter; PRE: pre-left ventricle assist device implantation; POST: immediately after LVAD implantation; RA: right atrial; RV: right ventricular; RVDD: right ventricular end-diastolic diameter; SD: standard deviation; TAPSE: tricuspid annular plane systolic excursion. The evolution over 5 time points—pre-LVAD, immediately after and at 1-, 2- and 3-year follow-up—was modelled after 4 parameters (LVDD, RVDD, TAPSE and RV-RA pressure gradient) for both groups. The results of the statistical analyses indicate that a statistically significant interaction between time and MR severity could not be detected for any of these parameters (see Supplementary Material and Fig. 1), i.e. there was no evidence that the profiles differed over time in terms of MR severity and that the difference between the 2 groups changed over time. For all parameters, except RVDD, a statistically significant effect of time was observed, with generally a large change at the first time point and without any significant change thereafter. Decrease in LVDD dimension, in both groups, occurred immediately after LVAD implantation, by a mean value of −5.2 mm (95% confidence interval −6.8 to −3.5 mm, P <0.001). The RV-RA pressure gradient decreased significantly immediately after LVAD implantation [−13.2 mmHg (95% confidence interval −17.0; −9.3 mmHg), P < 0.001]. RVDD values did not register a significant change over time, whereas the TAPSE value decreased in both groups [−2.3 mm (95% confidence interval −3.0; −1.7 mm); P < 0.001]. Differences in LVDD, RV-RA pressure gradient and RVDD detected between the groups were due to differences in baseline values. The evolution of MR and TR was modelled for the 5 time points as described earlier and also for the last follow-up available at 4–5 years after LVAD implantation. We observed a significant decrease in the severity of both MR and TR after LVAD implantation (Figs 2 and 3) with a drop in severity immediately after LVAD implantation (P < 0.001) and no significant change over time afterwards. Of the 65 patients with severe MR, only 5 continued to have severe MR at the end of the follow-up. Figure 2: View largeDownload slide MR severity throughout follow-up. The number of patients undergoing echocardiography at each specified follow-up time and for each MR severity grade is depicted inside or above the corresponding bar segment. LVAD: left ventricle assist device; MR: mitral regurgitation. Figure 2: View largeDownload slide MR severity throughout follow-up. The number of patients undergoing echocardiography at each specified follow-up time and for each MR severity grade is depicted inside or above the corresponding bar segment. LVAD: left ventricle assist device; MR: mitral regurgitation. Figure 3: View largeDownload slide TR severity throughout follow-up. The number of patients undergoing echocardiography at each specified follow-up time and for each TR severity grade is depicted inside or above the corresponding bar segment. LVAD: left ventricle assist device; TR: tricuspid regurgitation. Figure 3: View largeDownload slide TR severity throughout follow-up. The number of patients undergoing echocardiography at each specified follow-up time and for each TR severity grade is depicted inside or above the corresponding bar segment. LVAD: left ventricle assist device; TR: tricuspid regurgitation. Only patients with perioperative MR intervention were excluded, and so we observed the same improvement in MR severity in patients with prior MV reconstruction or MitraClip. The same improvement was observed for severe TR, including the 7 patients with prior tricuspid valve reconstruction. Pre-LVAD implantation, Group A demonstrated more patients with severe TR (26 of 65 in Group A and 12 of 63 in Group B, P = 0.009), but this difference was not observed at the end of the follow-up (10 of 65 in Group A and 3 of 63 patients in Group B, P = 0.76). In terms of complications (Table 2) after LVAD implantation, there was no association between the severity of MR and the postoperative rate of right heart failure, pump thrombosis, ventricular arrhythmias, bleeding, ischemic stroke or suction events. Table 2: Complications Total (n = 128) Not severe MR (n = 63) Severe MR (n = 65) P-value Death, n (%) 22 (17) 11 (18) 11 (17) 1 Cardiac death, n (%) 8 (6) 6 (9.5) 2 (3) 0.16 Heart transplantation, n (%) 22 (17) 14 (22) 8 (12) 0.16 ECMO, n (%) 5 (4) 2 (3) 3 (5) 1 RVAD, n (%) 4 (3) 1 (2) 3 (5) 0.62 HU listing for RHF, n (%) 6 (5) 3 (5) 3 (5) 1 ECMO + RVAD + HU, n (%) 11 (9) 5 (8) 6 (9) 1 Suction events, n (%)a 8 (6) 5 (8) 3 (5) 0.49 Pump thrombosis, n (%)a 8 (6) 3 (5) 5 (8) 0.72 VT requiring hospital visit/admission, n (%)a 20 (16) 13 (20) 7 (11) 0.15 Ischemic stroke, n (%)a 1 (0.7) 1 (1.6) 0 0.31 Intracerebral bleeding, n (%)a 3 (2.3) 3 (4.7) 0 0.75 HU listing for GIB, n (%)a 1 (0.7) 0 1 (1.5) 0.32 NYHA Class ≥III, n/n sample (%)  First post-LVAD 68/128 (53) 36/63 (57) 32/65 (49) 0.47  1-year follow-up 50/115 (44) 24/57 (42) 26/58 (45) 0.85 6MWT (m), mean ± SD 365.5 ± 107.2 367.3 ± 112.9 363.6 ± 102.8 0.89  Sample group size, n 61 31 30 Total (n = 128) Not severe MR (n = 63) Severe MR (n = 65) P-value Death, n (%) 22 (17) 11 (18) 11 (17) 1 Cardiac death, n (%) 8 (6) 6 (9.5) 2 (3) 0.16 Heart transplantation, n (%) 22 (17) 14 (22) 8 (12) 0.16 ECMO, n (%) 5 (4) 2 (3) 3 (5) 1 RVAD, n (%) 4 (3) 1 (2) 3 (5) 0.62 HU listing for RHF, n (%) 6 (5) 3 (5) 3 (5) 1 ECMO + RVAD + HU, n (%) 11 (9) 5 (8) 6 (9) 1 Suction events, n (%)a 8 (6) 5 (8) 3 (5) 0.49 Pump thrombosis, n (%)a 8 (6) 3 (5) 5 (8) 0.72 VT requiring hospital visit/admission, n (%)a 20 (16) 13 (20) 7 (11) 0.15 Ischemic stroke, n (%)a 1 (0.7) 1 (1.6) 0 0.31 Intracerebral bleeding, n (%)a 3 (2.3) 3 (4.7) 0 0.75 HU listing for GIB, n (%)a 1 (0.7) 0 1 (1.5) 0.32 NYHA Class ≥III, n/n sample (%)  First post-LVAD 68/128 (53) 36/63 (57) 32/65 (49) 0.47  1-year follow-up 50/115 (44) 24/57 (42) 26/58 (45) 0.85 6MWT (m), mean ± SD 365.5 ± 107.2 367.3 ± 112.9 363.6 ± 102.8 0.89  Sample group size, n 61 31 30 a The number of patients who had the specific complication (irrespective of how many episodes of the complication in each patient). ECMO: extracorporeal membrane oxygenation; GIB: gastrointestinal bleeding; HU-listing: high urgency listing; LVAD: left ventricular assist device; 6MWT: six minutes walking test; MR: mitral regurgitation; NYHA: New York Heart Association; RHF: right heart failure; RVAD: right ventricular assist device; SD: standard deviation; VT: ventricular tachycardia. Table 2: Complications Total (n = 128) Not severe MR (n = 63) Severe MR (n = 65) P-value Death, n (%) 22 (17) 11 (18) 11 (17) 1 Cardiac death, n (%) 8 (6) 6 (9.5) 2 (3) 0.16 Heart transplantation, n (%) 22 (17) 14 (22) 8 (12) 0.16 ECMO, n (%) 5 (4) 2 (3) 3 (5) 1 RVAD, n (%) 4 (3) 1 (2) 3 (5) 0.62 HU listing for RHF, n (%) 6 (5) 3 (5) 3 (5) 1 ECMO + RVAD + HU, n (%) 11 (9) 5 (8) 6 (9) 1 Suction events, n (%)a 8 (6) 5 (8) 3 (5) 0.49 Pump thrombosis, n (%)a 8 (6) 3 (5) 5 (8) 0.72 VT requiring hospital visit/admission, n (%)a 20 (16) 13 (20) 7 (11) 0.15 Ischemic stroke, n (%)a 1 (0.7) 1 (1.6) 0 0.31 Intracerebral bleeding, n (%)a 3 (2.3) 3 (4.7) 0 0.75 HU listing for GIB, n (%)a 1 (0.7) 0 1 (1.5) 0.32 NYHA Class ≥III, n/n sample (%)  First post-LVAD 68/128 (53) 36/63 (57) 32/65 (49) 0.47  1-year follow-up 50/115 (44) 24/57 (42) 26/58 (45) 0.85 6MWT (m), mean ± SD 365.5 ± 107.2 367.3 ± 112.9 363.6 ± 102.8 0.89  Sample group size, n 61 31 30 Total (n = 128) Not severe MR (n = 63) Severe MR (n = 65) P-value Death, n (%) 22 (17) 11 (18) 11 (17) 1 Cardiac death, n (%) 8 (6) 6 (9.5) 2 (3) 0.16 Heart transplantation, n (%) 22 (17) 14 (22) 8 (12) 0.16 ECMO, n (%) 5 (4) 2 (3) 3 (5) 1 RVAD, n (%) 4 (3) 1 (2) 3 (5) 0.62 HU listing for RHF, n (%) 6 (5) 3 (5) 3 (5) 1 ECMO + RVAD + HU, n (%) 11 (9) 5 (8) 6 (9) 1 Suction events, n (%)a 8 (6) 5 (8) 3 (5) 0.49 Pump thrombosis, n (%)a 8 (6) 3 (5) 5 (8) 0.72 VT requiring hospital visit/admission, n (%)a 20 (16) 13 (20) 7 (11) 0.15 Ischemic stroke, n (%)a 1 (0.7) 1 (1.6) 0 0.31 Intracerebral bleeding, n (%)a 3 (2.3) 3 (4.7) 0 0.75 HU listing for GIB, n (%)a 1 (0.7) 0 1 (1.5) 0.32 NYHA Class ≥III, n/n sample (%)  First post-LVAD 68/128 (53) 36/63 (57) 32/65 (49) 0.47  1-year follow-up 50/115 (44) 24/57 (42) 26/58 (45) 0.85 6MWT (m), mean ± SD 365.5 ± 107.2 367.3 ± 112.9 363.6 ± 102.8 0.89  Sample group size, n 61 31 30 a The number of patients who had the specific complication (irrespective of how many episodes of the complication in each patient). ECMO: extracorporeal membrane oxygenation; GIB: gastrointestinal bleeding; HU-listing: high urgency listing; LVAD: left ventricular assist device; 6MWT: six minutes walking test; MR: mitral regurgitation; NYHA: New York Heart Association; RHF: right heart failure; RVAD: right ventricular assist device; SD: standard deviation; VT: ventricular tachycardia. There was also no difference in the occurrence of clinically significant aortic valve insufficiency or closed aortic valve. Patients in both groups had a similar clinical status, which was assessed using the six-minute walking test and the NYHA class. During follow-up, 8 patients demonstrated severe MR, of whom 5 patients had persistent preoperative severe MR and 3 patients developed de novo severe MR. The presence of severe MR at the final follow-up was associated with poor unloading of the LV and with higher rate of hospital admissions [1 (0.25–2.75) vs 0 (0–1) per year P = 0.016]. The main reason for hospital admission in those patients with severe MR at the end of the follow-up was ventricular tachycardia. At the time of the final assessment, no difference was observed in survival between groups (Fig. 4). Figure 4: View largeDownload slide The Kaplan–Meier survival curves in patients with and without severe MR pre-LVAD implantation (the log-rank Mantel Cox P-value = 0.974). LVAD: left ventricle assist device; MR: mitral regurgitation. Figure 4: View largeDownload slide The Kaplan–Meier survival curves in patients with and without severe MR pre-LVAD implantation (the log-rank Mantel Cox P-value = 0.974). LVAD: left ventricle assist device; MR: mitral regurgitation. DISCUSSION Mitral regurgitation The reversibility of MR after LVAD implantation has already been well described [3–6]. Nevertheless, apart from verifying these findings in our study population, we analysed for the first time the clinical association between preoperative severe MR in patients undergoing LVAD implantation and haemodynamic changes affecting pulmonary circulation, right heart function and outcomes over a prolonged follow-up period. MR is a common finding in patients with heart failure, and it correlates with the severity of the disease [9]. Accordingly, we observed greater LV end-diastolic diameters in the severe MR group, suggesting a more advanced stage of remodelling of the left heart, leading to annular dilatation and consecutive loss of coaptation of the valve leaflets. Despite a more advanced state of heart failure, this LV remodelling seems to be reversible in a large majority of LVAD patients. In our study population, we observed that LVDD decreased immediately after LVAD implantation in both groups to a similar degree and that the LVDD remained higher in the severe MR group during follow-up. The significant decrease in LVDD, MR severity and subsequent RV-RA gradient occurred predominantly within the time interval from implantation to the first echocardiographic follow-up. This effect was maintained at 1 year and until the 3 years follow-up, but without further significant change as observed within the first postoperative period. The device-specific pump speed was similar between groups. These observations demonstrate the ability of the LVAD to unload the LV irrespective of the initial LV dimension or MR severity. The unloading of the LV improves the mitral insufficiency in the severe MR group and provides the same outcomes when compared with the non-severe MR group. This also suggests that MR reversal is a good marker of efficient LV unloading. Both groups included a similar number of patients who underwent MV repair and the MitraClip prior to LVAD implantation. The same improvement of MR severity was observed both in this subgroup and in patients with native valve anatomy, suggesting a benefit of LVAD therapy in this patient category as well. Of the 65 patients with severe MR, only 5 patients continued to have severe MR at the last follow-up, and at the end of the follow-up, only 3 additional patients progressed to severe MR (1 patient from Group A, who initially improved and 2 patients from Group B). The 8 patients with severe MR at their last outpatient visit had poor LV unloading and more hospital readmissions due to cardiovascular causes, suggesting a reduced benefit from LVAD therapy. This was only an observation. No relevant conclusion can be drawn from such a small patient number, but a recent study by Kassis et al. [10] showed the association between persistent severe MR and adverse outcomes in LVAD patients. Kitada et al. [11] suggested that posterior displacement of MV leaflets predicted persistent MR 1 week after LVAD implantation, without affecting major adverse outcomes at 1-year follow-up; however, long-term follow-up data are still missing. Further prospective and large population studies are needed to assess this issue. The pattern of MR reversal demonstrated in our patient cohort suggests that the presence of persistent severe MR detected at the early post-LVAD echocardiographic study should trigger research on additional therapy strategies, knowing that the degree of MR will not improve on its own and could increase the likelihood of adverse outcomes of this subgroup of patients. To date, conflicting evidence from retrospective studies still creates controversy about the surgical treatment of MR at the time of LVAD implantation. A multicentric study by Stulak et al. [7] comparing outcomes in patients with preoperative moderate to severe MR with those with mild MR pleaded in favour of no valve intervention. In contrast, a recent monocentric comparison study of Tanaka et al. [12] showed that the preoperative moderate to severe MR group with ‘spontaneous’ correction after LVAD implantation still had worse outcomes at 1-year follow-up (i.e. survival and freedom of MR) when compared with the group with concomitant ‘surgical’ correction of the MR, but no difference in hospital admissions was noted, and clinical status was not assessed. Furthermore, we can speculate, in the light of recent observations about LV recovery in LVAD patients, that only at the time of LVAD explantation MV repair should be considered. This issue further stresses the importance of future multicentre prospective studies addressing predictors of persistent MR and comparing outcomes with different approaches for a refined and adequate individual decision-making process for LVAD candidates. Right ventricular function and failure RV failure is one of the most feared complications after LVAD implantation [13, 14]. There is no conclusive evidence regarding predictors of post-LVAD RV failure implantation or selection of those who would benefit from elective biventricular assist device implantation. The current definition of right heart failure (RHF) is based mainly on haemodynamic and therapeutic criteria, not on echocardiographic parameters [15]; however, a prospective study analysing echocardiographic parameters prior to and after LVAD implantation is in progress [16]. In our study population, there was no difference between groups in terms of late RHF defined as the necessity of RVAD or extracorporeal membrane oxygenation implantation, or listing for heart transplantation due to RHF. This may suggest that severe MR is not necessarily associated with advanced RV dysfunction due to increased afterload in the long-term follow-up but rather a reversible mechanism with a good chance of regression after LVAD implantation. As noted above, there were no differences in pump speed and LVDD reduction between groups suggesting that there is no additional preload for the RV after LVAD implantation in patients with preoperative severe MR. Indeed, as shown in the retrospective studies, RV function improved in the majority of LVAD patients [17, 18]. The unloading of the LV decreased pulmonary pressure [19], and thus, the additional preload due to increased venous return could still be managed by the RV. New data has suggested that even though RV afterload reduction occurred after LVAD implantation, the RV did not immediately adapt to the increased preload after implantation; rather, it adapts progressively over time [20]. We evaluated right heart function by measuring TAPSE, RVDD and TR grade. In our population, we noticed a significant decrease in TAPSE in all patients after LVAD implantation, which did not change significantly afterwards. To our knowledge, only 1 study showed an improvement in TAPSE values after LVAD implantation [17], whereas another study described a reduction in TAPSE [21]. Two studies showed that TAPSE was not reliable after cardiac surgery: TAPSE was decreased after cardiothomy, without a reduction in the RV function measured using 3D echo or deformation imaging [22, 23]. Moreover, the decrease in TAPSE was a result of a change in the RV and LV interdependence after LVAD implantation with fixation of the LV to the inflow cannula. Therefore, semiquantitative or quantitative RV function assessment, or a combination of TAPSE, TR severity and RV dimensions was recommended [18, 24]. On the other hand, although TAPSE decreased in all patients, we noticed significantly lower values in patients who developed RHF at a later stage (10.73 ± 2.9 vs 13.15 ± 2.6 mm, P <0.001). This suggests that an absolute value of TAPSE after LVAD implantation could still be used to identify patients at risk of RHF. In our study, the small number of patients with severe RHF (n = 8) did not allow us to determine a new cut-off regarding TAPSE value as a predictor of severe RV dysfunction. Some studies imply that TAPSE may decrease when the RV does not have to pump against a high afterload and that it is a predictor of RV dysfunction only if it is associated with persistent significant TR [25, 21]. In our study population, TR severity decreased significantly without any intervention on the valve. Although TAPSE decreased in the whole population, there were only a small number of patients with persistent severe TR (Fig. 3). This suggests that the assessment of TR severity in combination with TAPSE after LVAD is a better marker of RV function and may also be a better predictor of late adverse outcomes, which should be evaluated in a larger cohort of patients. Left ventricular assist device and tricuspid regurgitation The current indication of the ISHLT guideline is to consider tricuspid valve repair if the patient presents with moderate to severe TR before LVAD implantation [2]. Small studies have shown a trend toward improved survival and improved early clinical outcomes such as length of inotropic infusion, renal insufficiency post-LVAD and length of hospital stay after tricuspid valve repair during LVAD insertion [26–29]. However, a meta-analysis of these studies did not show a difference in early outcomes, renal failure or necessity of RVAD implantation [30]. The majority of studies favour tricuspid valve repair because it was not associated with significant increase in operative risk. Because of our patient selection, we cannot comment on the early RV failure incidence in patients with severe TR, but we did notice a definite improvement in TR at the first echocardiography, which was maintained throughout the follow-up (Fig. 3). We also observed that Group A developed significantly more severe TR before LVAD implantation. This difference disappeared at the last follow-up. This may suggest that the 2 pathologies were linked as they improved synergistically after LVAD implantation. Although patients with severe MR and TR may be considered to be in a more advanced phase of the disease, our findings suggest that LVADs have a good therapeutic potential in these patients. Mortality and outcomes after left ventricular assist device The overall survival of patients in our cohort seems to be better when compared with results from interagency registry for mechanically assisted circulatory support (INTERMACS) reports (69% vs 59% at 3 years) [1] because we selected patients with available pre- and post-LVAD echocardiography and thus have excluded those who died in the immediate postoperative period. Although in our study there was no statistically significant difference in intermediate survival between patients with severe and less than severe MR before LVAD implantation [1- and 3-year survival (87.7% vs 88.4% and 71.8% vs 66.6%) for Groups A and B, respectively, Fig. 4], a recent multicentre study showed even improved survival in patients with significant MR [7]. Limitations The retrospective nature with all its inherent limitations is a major limitation of this study. In our attempt to understand haemodynamic changes, we selected patients with good echocardiographic windows, thus introducing a bias especially with regard to patients who died early and did not have an echocardiographic study after LVAD implantation. We excluded the 4–5-year follow-up in the evaluation of LVDD, RVDD, RV-RA pressure gradient and TAPSE because of few available data at this time point. CONCLUSIONS Preoperative severe MR substantially decreases shortly after LVAD implantation in majority of the patients and is associated with unloading of the LV and decreased pulmonary pressure. This early effect is sustained during an intermediate follow-up period, suggesting that improvement in MR should be observed at the first postoperative echocardiographic study. Additionally, patients with severe MR pre-LVAD had similar functional status, complication rates and survival as patients with non-severe MR prior to LVAD implantation. 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Impact of tricuspid valve regurgitation in patients treated with implantable left ventricular assist devices . Ann Thorac Surg 2011 ; 91 : 1342 – 6 ; discussion 1346–7. Google Scholar CrossRef Search ADS PubMed 27 Piacentino V 3rd , Troupes CD , Ganapathi AM , Blue LJ , Mackensen GB , Swaminathan M et al. Clinical impact of concomitant tricuspid valve procedures during left ventricular assist device implantation . Ann Thorac Surg 2011 ; 92 : 1414 – 8 ; discussion 1418–9 Google Scholar CrossRef Search ADS PubMed 28 Saeed D , Kidambi T , Shalli S , Lapin B , Malaisrie SC , Lee R et al. Tricuspid valve repair with left ventricular assist device implantation: is it warranted? J Heart Lung Transplant 2011 ; 30 : 530 – 5 . Google Scholar CrossRef Search ADS PubMed 29 Piacentino V 3rd , Ganapathi AM , Stafford-Smith M , Hsieh MK , Patel CB , Simeone AA et al. Utility of concomitant tricuspid valve procedures for patients undergoing implantation of a continuous-flow left ventricular device . J Thorac Cardiovasc Surg 2012 ; 144 : 1217 – 21 . Google Scholar CrossRef Search ADS PubMed 30 Dunlay SM , Deo SV , Park SJ. Impact of tricuspid valve surgery at the time of left ventricular assist device insertion on postoperative outcomes . ASAIO J 2015 ; 61 : 15 – 20 . Google Scholar CrossRef Search ADS PubMed © The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

Journal

European Journal of Cardio-Thoracic SurgeryOxford University Press

Published: Jan 16, 2018

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