European Journal of Heart Failure (2012) 14, 939–945 doi:10.1093/eurjhf/hfs069
Acute effect of percutaneous MitraClip therapy in patients with haemodynamic decompensation Simon Biner1,2†, Robert J. Siegel1*†, Ted Feldman3, Asim M. Rafique1, Alfredo Trento1, Patrick Whitlow4, Jason Rogers 5, Marc Moon 6, Brian Lindman 6, Alan Zajarias 6, Donald Glower 7, and Saibal Kar 1 on behalf of the EVEREST investigators 1 Cedars-Sinai Heart Institute, Los Angeles, CA 90048, USA; 2Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; 3Evanston Hospital, Evanston, IL, USA; 4The Cleveland Clinic, Cleveland, OH, USA; 5University of California Davis Medical Center, Sacramento, CA, USA; 6Washington University School of Medicine, Saint Louis, MO, USA; and 7Duke University Medical Center, Durham, NC, USA
Received 31 January 2012; revised 26 March 2012; accepted 30 March 2012; online publish-ahead-of-print 14 May 2012
Aims
To evaluate the haemodynamic effect of acute procedural success (APS) after MitraClip therapy in patients with haemodynamic decompensation. ..................................................................................................................................................................................... Methods Of 107 patients, 79 achieved APS after MitraClip implantation. The increase in cardiac index (CI) was primarily and results detected in patients with a low baseline CI (2.0 + 0.5 to 2.5 + 5 L/min/m2, P , 0.001). There was a decrease in left ventricular end-diastolic pressure (LVEDP) (20 + 5 to 13 + 5 mmHg, P ¼ 0.002) and mean pulmonary capillary wedge pressure (PCWPm) (20 + 4 to 16 + 5 mmHg, P ¼ 0.001) in patients with values .15 mmHg at baseline, and a decrease in mean pulmonary artery systolic (PAPm) (36 + 4 to 29 + 7 mmHg P ¼ 0.003) in those with values .30 mmHg before the MitraClip procedure. Patients with decompensation compared with patients with compensation experienced significant reduction in LVEDP (–8.3 + 11.9 mmHg vs. –0.2 + 4.5 mmHg, P ¼ 0.009), a reduction in PCWPm ( –3.5 + 5.6 mmHg vs. 1.9 + 4.7 mmHg, P , 0.001), and a reduction in PAPm ( –8 + 9 mmHg vs. 3 + 6 mmHg, P , 0.001). ..................................................................................................................................................................................... Conclusion The favourable haemodynamic effects of MitraClip therapy on CI were primarily detected in patients with low CI before the procedure, and improvements in left-sided filling pressure and PAP were primarily seen in those with elevated values at baseline.
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Mitral regurgitation † MitraClip † Haemodynamics
Introduction Percutaneous mitral valve (MV) repair with the MitraClip device is an important advance in the treatment of patients with mitral regurgitation (MR). The Endovascular Valve Edge-to-Edge Repair Study (EVEREST II), a randomized controlled comparison of percutaneous mitral repair and MV surgery, compared the efficacy and safety of percutaneous MV repair with conventional surgical repair or replacement. EVEREST II demonstrated that percutaneous MV repair was less effective at reducing MR than surgery; however, the procedure was safer and provided similar improvement in clinical outcomes.1 Subsequently, MitraClip therapy has
been shown to be an effective treatment modality in patients with MR and advanced heart failure.2 – 4 We recently reported the acute haemodynamic effects of percutaneous MV repair with the MitraClip device in a nonrandomized cohort of patients, 80% of whom had degenerative MR.5 MitraClip therapy was associated with an increase in forward stroke volume and cardiac index (CI), and a decrease in left ventricular end-diastolic pressure (LVEDP). Subsequently it has been shown that MitraClip valve repair results in enhanced forward ejection in functional MR.6 In addition, the type of endovascular repair results in a reduction in pulmonary capillary wedge pressure (PCWP) and pulmonary artery pressure (PAP).6
†These authors contributed equally to this work.
* Corresponding author. Tel: +1 310 423 3849, Fax: +1 310 423 8571, Email:
[email protected] Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2012. For permissions please email:
[email protected].
940 In patients with severe MR, low forward cardiac output and elevated left-sided filling pressure adversely affect the clinical course and prognosis.7 – 9 Pulmonary hypertension in the setting of MR may compromise short- and long-term survival even with surgical correction of MR.10,11 As patients with severe MR and haemodynamic decompensation are at high risk of cardiac events, it is important to evaluate the effect of the endovascular intervention in this population. The objective of this study was to assess the haemodynamic effect of successful MitraClip therapy in a subgroup of patients with haemodynamic decompensation.
Methods Patients We performed a post-hoc subgroup analysis of patients treated in the EVEREST phase I feasibility trial and in the roll-in phase of the EVEREST II pivotal trial.1,12,13 All patients had moderate to severe (3+) or severe (4+) MR according to the criteria of the American Society of Echocardiography.14 If patients were asymptomatic they were required to have abnormal LV systolic function (LV ejection fraction of ,60% or left ventricular end-systolic dimension .40 mm). The key anatomic inclusion criteria included: (i) for patients with functional MR, coaptation length of at least 2 mm and a coaptation depth of ,11 mm; and (ii) for patients with degenerative MR, leaflet flail, a flail gap ,10 mm, and a flail width ,15 mm. Patients were excluded if there was: (i) evidence of an acute myocardial infarction in the 12 weeks prior to the index procedure; (ii) need for any other cardiac surgery including surgery for coronary artery disease (CAD), atrial fibrillation, pulmonic, aortic, or tricuspid valve disease; or (iii) any endovascular therapeutic intervention or surgical procedure performed within 30 days prior to the index procedure.
Echocardiography Trans-thoracic echocardiograms were obtained by an identical echocardiographic protocol in all participating centres. Quantitative measurements [LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV internal diastolic dimension (LVIDd), LV internal systolic dimension (LVIDs), effective regurgitant orifice area (EROA), regurgitant volume (RV), regurgitant fraction (RF), forward stroke volume (FSV), as well as MR grade from 1+ to 4 +] were made at the core laboratory (University of California at San Francisco).1,13
Percutaneous mitral valve repair procedure The procedure was performed under general anaesthesia using transesophageal echocardiography guidance and fluoroscopy. The MitraClip device was advanced following an echo-guided transseptal catheterization to the left atrium and across the MV to the LV. The leaflets were grasped by pullback and the arms of the clip were closed. The adequate reduction of MR severity was assessed by Doppler echocardiography.1,13
Cardiac catheterization All haemodynamic evaluation was performed under general anaesthesia. Patients were studied prior to and within 15 min following attempted MitraClip device deployment. LVEDP was measured by a fluid-filled catheter advanced from the femoral artery. Left arterial (LA) pressure was obtained from the transseptal catheter placed in the left artery or by measurement of the PCWP. Systolic, diastolic,
S. Biner et al.
and mean PAP, as well as PCWP were obtained using a balloon-tipped Swan – Ganz catheter. The measurements were assessed at end expiration and were expressed as an average of five cardiac cycles. Cardiac output was determined by the Fick or the thermodilution method depending on the preference of the site.15
Haemodynamic subgroups Acute procedural success (APS) was defined as a reduction of MR to ≤ 2+ following MitraClip placement. Haemodynamic decompensation was defined as one of the following: baseline CI ,2.5 L/min/m2, LVEDP ≥ 15 mmHg, mean PCWP ≥ 15 mmHg, or systolic PAP .40 mmHg. We analysed patients with APS according to baseline CI: low (,2.5 L/min/m2), normal (2.5– 3.6 L/min/m2), or high (.3.6 L/min/m2). Patients were also subdivided into groups with normal LVEDP ( ≤ 15 mmHg) vs. those with an elevated LVEDP (.15 mmHg), and normal or near normal PCWP ( ≤ 15 mmHg) vs. those with elevated mean PCWP (.15 mmHg). Similarly those with normal to mild elevations of systolic PAP (,40 mmHg) and mean (,30 mmHg) PAP were compared with those with elevated systolic PAP ( ≥ 40 mmHg) and mean ( ≥ 30 mmHg) PAP.16
Statistical analysis Analysis was performed with the use of the statistical software program SPSS V.18.0. Continuous variables are presented as mean + SD. Categorical data are presented as absolute numbers or percentages. Haemodynamic data prior to and following MitraClip deployment were compared using paired t-test. Comparisons between groups were performed using independent t-test. Levene’s test was performed to assess the homogeneity of variance. The x2 test was done for the comparison of categorical data. Pearson’s correlation was used to determine possible linear relationships between variables. A correlation coefficient r ≥ 0.2 was considered substantial and was further assessed for significance. A P-value of , 0.05 was considered statistically significant.
Results The MitraClip device was implanted in 96 (90%) of the patients in whom it was attempted. APS was achieved in 79 (74%) patients. Clinical, echo Doppler, and invasive haemodynamic characteristics for the entire cohort as well as those with APS are presented in Table 1. As shown in Table 2, in patients with APS, there was a significant increase in CI and a significant reduction in LVEDP. In addition there was an insignificant trend to a reduction of PCWP V waves, and no significant change in mean PCWP and systolic, diastolic, and mean PAP (Table 2). In contrast, for patients with no APS, there was no significant change in CI, PCWP V wave, or mean PCWP (P . 0.1). In addition, in patients with no APS, there was an insignificant trend towards an increase in systolic, diastolic, and mean PAP.
Correlation between baseline invasive and echo Doppler variables Further analysis was done on the patients with APS to assess the correlation between multiple invasive haemodynamic variables and LV dimensions and volumes (i.e. FSV, EDV, ESV, LVIDd, and LVIDs) obtained by echo Doppler. As shown in Table 3, there was a trend to a weak correlation between FSV and cardiac output (P ¼ 0.05). LVESV correlated significantly with LVEDP
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MitraClip therapy in patients with haemodynamic decompensation
Table 1 Baseline patient characteristics All patients (n 5 107)
Patients with APS (n 5 79)
............................................................................................................................................................................... Age (mean)
67 + 14
68 + 15
≥70 years NYHA functional class III–IV
53% 46%
56% 53%
Degenerative MR
84 (79%)
76%
MR grade (+) Ischaemic/dilated
3.3 + 0.7 23 (21%)
3.2 + 0.7 24%
LVIDd (cm)
5.6 + 0.6
5.6 + 0.6
LVIDs (cm) LVEDV (mL)
3.5 + 0.8 172 + 38
3.5 + 0.8 169 + 38
LVESV (mL)
70 + 25
69 + 27
LVEF (%) TR grade (+)
57 + 10 1.0 + 0.5
60 + 9 –
CI (L/min/m2) LVESP (mmHg) LVEDP (mmHg)
2.7 + 1.0
2.7 + 1.0
105 + 23 10.5 + 8.5
107 + 23 11 + 8.9
PCWP V wave (mmHg)
20.5 + 12.8
20.4 + 13.4
Mean PCWP (mmHg) Systolic PAP (mmHg)
14.8 + 6.3 34 + 12
14.8 + 5.8 35 + 11
Diastolic PAP (mmHg)
15 + 7
15 + 7
Mean PAP (mmHg) Systolic SAP (mmHg)
24 + 11 107 + 23
23 + 9 109 + 24
Diastolic SAP (mmHg) Mean SAP (mmHg) SVR (dyne/s/cm5) PVR (dyne/s/cm5)
57 + 15
57 + 15
75 + 17 1222 + 551
76 + 12 1239 + 504
161 + 209
155 + 112
APS, acute procedural success; CI, cardiac index; LVEDP, left ventricular end-diastolic pressure; LVEDV, left ventricular end-diastolic volume; LVEF, left ventricular ejection fraction; LVESP, left ventricular end-systolic pressure; LVESV, left ventricular end-systolic volume; LVIDd, left ventricular end-diastolic dimension; LVIDs, left ventricular end-systolic dimension; MR, mitral regurgitation; NYHA, New York Heart Association functional class; PAP, pulmonary artery pressure; PCWP, pulmonary capillary wedge pressure; PVR, pulmonary vascular resistance; SAP, systemic arterial pressure; SVR, systemic vascular resistance; TR, tricuspid regurgitation.
(P ¼ 0.034), mean PCWP (P ¼ 0.01), systolic PAP (P , 0.001), diastolic PAP (P , 0.001), and mean PAP (P ¼ 0.001). There was a weak positive correlation between LVIDs and systolic PAP (P ¼ 0.001), diastolic PAP (P ¼ 0.001), and mean PAP (P , 0.001). However, there was no significant correlation found between enddiastolic echo variables (LVEDV and LVIDd) and invasive parameters.
Correlation between baseline and post-MitraClip haemodynamic variables To better understand the haemodynamic response to successful MitraClip therapy, we evaluated the correlation between the baseline values of individual variables and the magnitude of the change in the same variable as a result of APS. We found a moderate inverse correlation between baseline CI and the absolute change in CI after MitraClip insertion (r ¼ –0.5, P , 0.001), wherein a lower baseline CI was associated with greater improvement in CI. Similarly, an inverse correlation was observed between baseline filling pressures and the change in these parameters after MitraClip insertion: mean PCWP (r ¼ –0.58), systolic PAP (r ¼ –0.59), diastolic PAP (r ¼ –0.53), LVEDP (r ¼ –0.77), and PCWP V wave
(r ¼ –0.81). Higher filling pressures at baseline were associated with a larger decrease in filling pressures after the procedure. In addition, there was an inverse correlation between baseline values and the change in systemic vascular resistance (SVR) (r ¼ – 0.63) and pulmonary vascular resistance (PVR) (r ¼ –0.80), namely the higher the resistance the greater the decrease in SVR and PVR after APS. No significant correlation was observed between mean PAP and the reduction in MR.
Correlation between baseline left ventricular volumes and the haemodynamic response to MitraClip implantation Table 4 demonstrates correlation analysis between pre- and postprocedural invasive haemodynamic changes and baseline LV enddiastolic and LV end-systolic volumes in patients with APS. There was a weak positive correlation between baseline LVEDV and change in CI (P ¼ 0.07), and a weak negative correlation between baseline LVEDV and change in diastolic PAP (P ¼ 0.01). There was no substantial correlation between baseline LVEDV and changes in other haemodynamic variables.
942
S. Biner et al.
Table 2 Haemodynamic effect of MitraClip implantation in patients with acute procedural success vs. those without acute procedural success APS
. . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . Pre
P- value
Post
No APS
. . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . .
Pre
Post
P- value
............................................................................................................................................................................... CI (L/min/m2)
2.7 + 1.0
3.1 + 1.0
0.002
2.5 + 1.0
2.6 + 0.9
0.56
LVEDP (mmHg)
11 + 8.9
9 + 5.8
0.015
9+6
11 + 7
0.24
17.5 + 7.5 14.4 + 5.3
0.078 0.42
18 + 9 13 + 7
18 + 8 15 + 11
0.87 0.44
20.4 + 13.4 14.8 + 5.8
PCWP v wave (mmHg) PCWP mean (mmHg) Systolic PAP (mmHg)
35 + 11
35 + 9
0.51
30 + 9
46 + 12
0.1
Diastolic PAP (mmHg) Mean PAP (mmHg)
15 + 7 23 + 9
14 + 6 23 + 7
0.89 0.6
13 + 6 21 + 7
20 + 8 27 + 10
0.24 0.88
Values are given as mean + SD. APS, acute procedural success; CI, cardiac index; LVEDP, left ventricular end-diastolic pressure; PAP, pulmonary artery pressure; PCWP, pulmonary capillary wedge pressure.
Table 3 Correlation between initial echo Doppler and haemodynamic variables
Table 4 Correlation between baseline left ventricular volumes and the haemodynamic response to MitraClip implantation
FSV (mL) LVESV (mL) LVIDs (cm)
................................................................................ DCO (L/min)
0.20
NS
NS
DLVEDP (mmHg)
NS
0.22
NS
DPCWP V wave (mmHg) NS DMean PCWP (mmHg) NS
0.20 0.29
NS NS
DSystolic PAP (mmHg)
NS
0.36
0.30
DDiastolic PAP (mmHg) DMean PAP (mmHg)
NS NS
0.38 0.35
0.4 0.32
Non-significant (NS) ,0.20. APS, acute procedural success; CO, cardiac output; LVESV, left ventricular end-systolic volume; LVIDs, left ventricular end-systolic dimension; PAP, pulmonary artery pressure; PCWP, pulmonary capillary wedge pressure.
There was a weak positive correlation between baseline LVESV and change in LVEDP and diastolic PAP (P ¼ 0.002). There was weak negative correlation between baseline LVESV and change in LVSP (P ¼ 0.49), systolic PAP (P ¼ 0.034), and mean PAP (P ¼ 0.003). There was moderate negative correlation between baseline LVESV and diastolic PAP (P , 0.001).
Subgroup analysis The effects of the successful MitraClip therapy in patients with compensated and decompensated haemodynamic parameters are shown in Table 5. The patients with decompensated baseline parameters experienced favourable changes in most of the individual haemodynamic variables including indices of LV systolic function, LA and LV filling pressures, and PA pressure. In contrast, in those patients with compensated haemodynamics there was no significant change in CI, LVEDP, and PCWP V wave. Moreover, in the compensated subgroup, there was a significant increase in mean PCWP, as well as systolic, diastolic, and mean PAP.
Change
Correlation coefficient
...........................
LVEDV (mL)
LVESV (mL)
0.03 0.01
0.02 0.02
............................................................................... CO (L/min) CI (L/min/m2)
0.8 + 1.9 0.4 + 0.0
SVR (dyne/s/cm5)
–239 + 485
–0.16
–0.17
LVESP (mmHg) LVEDP (mmHg)
– 2 + 22 –2 + 6
–0.2 0.23
–0.21 0.34
PCWP V wave (mmHg)
–3 + 5
–0.13
–0.21
Mean PCWP (mmHg) Systolic PAP (mmHg)
0+1 0+2
0.15 –0.1
0.22 –0.22
Diastolic PAP (mmHg)
–1 + 0
–0.28
–0.41
0+8
–0.19
–0.32
Mean PAP (mmHg)
CI, cardiac index; CO, cardiac output; LVEDP, left ventricular end-diastolic pressure; LVEDV, left ventricular end-diastolic volume; LVESP, left ventricular end-systolic pressure; LVESV, left ventricular end-systolic volume; PAP, pulmonary artery pressure; PCWP, pulmonary capillary wedge pressure; SVR, systemic vascular resistance.
The comparison of the haemodynamic changes secondary to MitraClip treatment between MR patients with decompensated and compensated haemodynamic variables is shown in Table 6. The MR patients with decompensated haemodynamic variables demonstrated a significantly greater reduction in LVEDP, PCWP, and systolic, diastolic, and mean PAP. Sixty (76%) patients with APS had degenerative aetiology. There was no significant difference in haemodynamic response to MitraClip treatment between patients with degenerative and functional MR. To evaluate the effect of severity of symptoms on change in haemodynamic parameters after MitraClip, the patients with New York Heart Association (NYHA) functional class I– II
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MitraClip therapy in patients with haemodynamic decompensation
Table 5 Haemodynamic effects of MitraClip therapy in patients with compensated and decompensated haemodynamic variables Compensated
Decompensated
............................................................... n
Pre
Post
CI (L/min/m2)
33
3.4 + 1.0
3.7 + 1.1
LVEDP (mmHg)
49
7+4
7+5
PCWP V wave (mmHg) Mean PCWP (mmHg)
52 41
15 + 6 11 + 3
15 + 7 12 + 4
Systolic PAP (mmHg)
54
28 + 6
Diastolic PAP (mmHg) Mean PAP (mmHg)
53 49
8+3 19 + 5
...............................................................
P-value
n
Pre
Post
P-value
0.3
34
2.0 + 0.3
2.5 + 0.5
,0.001
0.8
17
20 + 5
13 + 5
0.002
0.7 0.016
16 32
37 + 17 20 + 4
23 + 6 16 + 5
0.01 0.001
32 + 8
,0.001
21
49 + 7
40 + 9
0.004
7+3 21 + 5
0.09 0.002
17 15
20 + 5 36 + 4
16 + 4 28 + 7
0.22 0.003
...............................................................................................................................................................................
CI, cardiac index; LVEDP, left ventricular end-diastolic pressure; PAP, pulmonary artery pressure; PCWP, pulmonary capillary wedge pressure.
Table 6 Comparison of response to MitraClip therapy between the patients with decompensated and compensated haemodynamic variables N
Compensated
N
Decompensated
P-value
............................................................................................................................................................................... DCI (L/min/m2)
33
0.3 + 1.4
34
0.6 + 0.5
DLVEDP (mmHg)
49
– 0.2 + 4.5
17
–8.3 + 11.9
0.009
DPCWP V wave (mmHg) DPCWP mean (mmHg)
52 41
0.5 + 7.7 1.9 + 4.7
16 32
– 11.8 + 16.3 –3.5 + 5.6
0.01 ,0.001
DSystolic PAP (mmHg)
54
4+7
21
–7 + 9
,0.001
DDiastolic PAP (mmHg) DMean PAP (mmHg)
53 49
1+3 3+6
17 15
22 + 6 28 + 9
0.07 ,0.001
0.2
CI, cardiac index; LVEDP, left ventricular end diastolic pressure; PAP, pulmonary artery pressure; PCWP, pulmonary capillary wedge pressure.
(n ¼ 58) and III –IV (n ¼ 49) were compared. There was a significantly greater reduction in MR in patients with NYHA class III – IV symptoms compared with NYHA class I– II symptoms (– 1.77 + 0.93 vs. –1.38 + 0.96, P ¼ 0.045). There was no significant difference in haemodynamic response to MitraClip treatment between patients with NYHA class III – IV symptoms compared with NYHA class I– II symptoms.
Discussion This is the first report to evaluate the haemodynamic response to successful MitraClip treatment in various haemodynamic subgroups. Patients with haemodynamic decompensation prior to the MitraClip experienced the greatest improvement, while the patients with normal or mildly abnormal baseline haemodynamic disturbances showed modest or insignificant change in their baseline values. An increase in CI was only observed in patients with a low CI at baseline. The combined group of patients with a normal or high baseline CI value had no significant change in CI. In patients with elevated filling pressures (PCWP, PCWP V wave, as well as LVEDP .15 mmHg) and elevated systolic PAP ( ≥ 40 mmHg), there was a significant decrease in filling pressures after successful MitraClip therapy. Moreover, the decrease in systolic PAP correlated with the drop in mean PCWP and the PCWP V wave.
The cardiovascular response to severe MR typically is characterized by volume overload and eccentric LV remodelling. Initially, changes in cardiac geometry allow accommodation of the regurgitant volume at low filling pressures. In the compensatory phase, an increased preload and low afterload (provided by the unloading of the LV and low impedance in the LA) facilitate LV ejection, leading to an increased total CI and maintenance of a normal forward CI. Chronic volume overload eventually induces LV systolic dysfunction. At this stage normal CI is maintained at the expense of elevated left-sided filling pressures. If the MR is left uncorrected there may be impairment of forward CI and additional elevation of the PCWP and PAP. Advanced age co-existent hypertension (i.e. increased systemic vascular resistance),17,18 LV systolic dysfunction (i.e. ischaemic cardiomyopathy or non-ischaemic dilated cardiomyopathy), as well as LV diastolic dysfunction associated with ageing and hypertension18 are additional cardiovascular abnormalities contributing to impaired cardiac output and elevated filling pressures in the setting of chronic, severe MR. In our study, 53% of the patients were 70 years of age or older, 69% had a history of hypertension, 21% had ischaemic cardiomyopathy, and 46% suffered from advanced congestive heart failure symptoms (NYHA functional class III –IV). The high proportion of elderly patients with multiple cardiovascular abnormalities appears to be the reason for low pre-procedural CI in 48% of
944 patients and the elevated mean PCWP and elevated systolic PAP in 46% and 51%, respectively. Mitral valve surgery in the elderly with advanced heart failure is associated with a high operative risk. Further haemodynamic deterioration and a low CI state in this setting is a common clinical concern. Uncertainty over treatment decisions often arises as the patient with MR may have such advanced disease that the risk of valve surgery is greater than the benefit of the procedure.19 Based on the aetiology of MR (i.e. functional or degenerative), operative treatment may include restrictive mitral annuloplasty, MV repair, or MV replacement with preservation of chordae tendineae. While surgery is generally effective in patients with severe MR, in patients with advanced haemodynamic disturbances the optimal treatment strategy is controversial.7,8 Our study shows that in patients with MR and haemodynamic decompensation, percutaneous MR reduction results in immediate haemodynamic improvement by increasing forward CI and unloading the left ventricle and left artery without increasing the risk of periprocedural deterioration.
Limitations The major limitation of our study is that this is a post-hoc analysis, and therefore the results should be considered hypothesis generating. All haemodynamic and cardiac output data were obtained under general anaesthesia before and after MitraClip placement. It is impossible to separate the effects of anaesthesia from the effects of MitraClip implantation on the haemodynamics. The role of intravenous hydration during this procedure on fasting patients who may have become relatively hypovolaemic at the beginning of the procedure is uncertain. Inotropic medications may have been administered over the course of the procedure and affected some of the haemodynamic variables. However, no patient developed low cardiac output (i.e. systolic blood pressure ,90 mmHg, and CI ,1.4 L/min/m2) that required inotropic support after MitraClip placement.
Conclusion Percutaneous MV repair with the MitraClip device leads to favourable haemodynamic changes in those patients with MR who are in a decompensated state. The improvements in haemodynamics were primarily observed in those patients with reduced CI and/ or elevated filling pressure prior to the clip placement.
S. Biner et al.
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Conflict of interest: R.J.S. is a speaker for Philips Ultrasound and a consultant for Abbott. T.F receives research support and is a consultant to Abbott, Edwards, Boston Scientific and Edwards Lifesciences. P.W. receives research support from Evalve. S.K. receives research grants and honoraria from and is a consultant to Abbott Vascular. All other authors have no relationships to disclose.
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References 1. Feldman T, Foster E, Glower DG, Kar S, Rinaldi MJ, Fail PS, Smalling RW, Siegel R, Rose GA, Engeron E, Loghin C, Trento A, Skipper ER, Fudge T, Letsou GV,
16.
Massaro JM, Mauri L; EVEREST II Investigators. Percutaneous repair or surgery for mitral regurgitation. N Engl J Med 2011;364:1395 – 1406. Franzen O, van der Heyden J, Schlu¨ter M, Baldus S, Schillinger W, Butter C, Hoffmann R, Corti R, Pedrazzini G, Swaans MJ, Neuss M, Gru¨nenfelder J, Eulenburg C, Reichenspurner H, Meinertz T, Auricchio A. MitraClip therapy in patients with end-stage systolic heart failure. Eur J Heart Fail 2011;13:569–576. Schillinger W, Athanasiou T, Weicken N, Berg L, Tichelba¨cker T, Puls M, Hu¨nlich M, Wachter R, Helms HJ, Seipelt R, Scho¨ndube FA, Hasenfuss G. Impact of the learning curve on outcomes after percutaneous mitral valve repair with MitraClip and lessons learned after the first 75 consecutive patients. Eur J Heart Fail 2011;13:1331 –1339. Auricchio A, Schillinger W, Meyer S, Maisano F, Hoffmann R, Ussia GP, Pedrazzini G, van der Heyden J, Fratini S, Klersy C, Komtebedde J, Franzen O. on behalf of the PERMIT-CARE investigators. Correction of mitral regurgitation in non-responders to cardiac resynchronization therapy by MitraClip improves symptoms and promotes reverse remodeling. J Am Coll Cardiol 2011;58: 2183 –2189. Siegel RJ, Biner S, Rafique AM, Rinaldi M, Lim S, Fail P, Hermiller J, Smalling R, Whitlow PL, Herrmann HC, Foster E, Feldman T, Glower D, Kar S; EVEREST Investigators. The acute hemodynamic effects of MitraClip therapy. J Am Coll Cardiol 2011;57:1658 –1665. Gaemperli O, Moccetti M, Surder D, Biaggi P, Hurlimann D, Kretschmar O, Buehler I, Bettex D, Felix C, Luscher TF, Falk V, Grunenfelder J, Corti R. Acute haemodynamic changes after percutaneous mitral valve repair: relation to mid-term outcomes. Heart 2012;98:126 – 132. Bonow RO, Carabello BA, Chatterjee K, de Leon AC Jr, Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O’Gara PT, O’Rourke RA, Otto CM, Shah PM, Shanewise JS; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2008 focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1998 guidelines for the management of patients with valvular heart disease). Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2008;52:e1 –142. Vahanian A, Baumgartner H, Bax J, Butchart E, Dion R, Filippatos G, Flachskampf F, Hall R, Iung B, Kasprzak J, Nataf P, Tornos P, Torracca L, Wenink A; Task Force on the Management of Valvular Hearth Disease of the European Society of Cardiology; ESC Committee for Practice Guidelines. Guidelines on the management of valvular heart disease: the Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology. Eur Heart J 2007;28:230 –268. Tribouilloy CM, Enriquez-Sarano M, Schaff HV, Orszulak TA, Bailey KR, Tajil AJ, Frye RL. Impact of preoperative symptoms on survival after surgical correction of organic mitral regurgitation: rationale for optimizing surgical indications. Circulation 1999;99:400 –405. Ghoreishi M, Evans CF, DeFilippi CR, Hobbs G, Young CA, Griffith BP, Gammie JS. Pulmonary hypertension adversely affects short- and long-term survival after mitral valve operation for mitral regurgitation: implications for timing of surgery. J Thorac Cardiovasc Surg 2011;142:1439 –1452. Feldman T, Wasserman HS, Herrmann HC, Gray W, Block PC, Whitlow P, St Goar F, Rodriguez L, Silvestry F, Schwartz A, Sanborn TA, Condado JA, Foster E. Percutaneous mitral valve repair using the edge-to-edge technique: sixmonth results of the EVEREST Phase I Clinical Trial. J Am Coll Cardiol 2005;46: 2134 –2140. Glover D, Young N, Alexander J, Gangahar D, Skipper E, Cleveland J, Trento A, Feldman T, on behalf of the EVEREST II investigators. EVEREST II randomized clinical trial: a clinical assessment of anatomical predictors of de novo mitral valve replacement or following MitraClip procedure. J Am Coll Cardiol 2010;56;B24. Zoghbi WA, Enriquez-Sarano M, Foster E, Grayburn PA, Kraft CD, Levine RA, Nihoyannopoulos P, Otto CM, Quinones MA, Rakowski H, Stewart WJ, Waggoner A, Weissman NJ; American Society of Echocardiography. Recommendations for evaluation of the severity of native valvular regurgitation with twodimensional and Doppler echocardiography. J Am Soc Echocardiogr 2003;16: 777 –802. Ganz W, Donoso R, Marcus HS, Forrester JS, Swan HJ. A new technique for measurement of cardiac output by thermodilution in man. Am J Cardiol 1971; 27:392 – 396. Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson LJ. Harrison’s Principles of Internal Medicine. 16th ed. New Yok: McGraw-Hill; 2005. Lakatta EG. Cardiovascular regulatory mechanisms in advanced age. Physiol Rev 1993;73:413 –467.
MitraClip therapy in patients with haemodynamic decompensation
17. Borlaug BA, Olson TP, Lam CS, Flood KS, Lerman A, Johnson BD, Redfield MM. Global cardiovascular reserve dysfunction in heart failure with preserved ejection fraction. J Am Coll Cardiol 2010;56:845 –854. 18. Mirabel M, Iung B, Baron G, Messika-Zeitoun D, De´taint D, Vanoverschelde JL, Butchart EG, Ravaud P, Vahanian A. What are the characteristics of patients
945 with severe, symptomatic, mitral regurgitation who are denied surgery? Eur Heart J 2007;28:1358 – 1365. 19. Enriquez-Sarano M, Loulmet DF, Burkhoff D. The conundrum of functional mitral regurgitation in chronic heart failure. J Am Coll Cardiol 2008;51: 487 – 489.
