© 2015, Wiley Periodicals, Inc. DOI: 10.1111/joic.12179
STRUCTURAL HEART DISEASE Effectiveness of MitraClip Therapy in Patients with Refractory Heart Failure MARIANNA ADAMO, M.D., 1 MARCO BARBANTI, M.D., 2 SALVATORE CURELLO, M.D., 1 CLAUDIA FIORINA, M.D., 1 ERMANNA CHIARI, M.D., 1 GIULIANO CHIZZOLA, M.D., 1 DAVIDE CAPODANNO, M.D., P H .D., 2 CORRADO TAMBURINO, M.D., P H .D., 2 MARCO METRA, M.D., 1 and FEDERICA ETTORI, M.D. 1 From the 1Spedali Civili, Brescia, Italy; and 2Ferrarotto Hospital, Catania, Italy
Objectives: To assess outcomes for MitraClip therapy in patients with refractory heart failure (HF) and mitral regurgitation (MR) 3þ. Background: The beneficial role of Mitraclip also in patients with severe HF has been reported. Methods: Out of 45 patients undergoing MitraClip implantation at our institute, 16 were on refractory HF defined as diuretics and/or inotropics infusion and/or IABP dependence (group A) or labile haemodynamic balance (group B). Results: Patients were aged 69 13 years and 75% were males. Group A (8 patients) had a mean hospitalization length before MitraClip procedure of 5333 days. Group B (8 patients) had a mean rate of hospitalization, in the last 50 days before procedure, of 254 days. Acute procedural success was observed in 94% of patients. All but one patients of group A were quickly weaned from pharmacologic and/or mechanical supports within 5 3 days from procedure and discharged at 2010 days. All patients of group B were discharged after 108 days from MitraClip. At 1 year: a) cumulative survival rate was 78%; b) all patients were in NYHA functional class II; c) residual MR 2 was observed in 90%; d) systolic pulmonary arterial pressure was significantly reduced compared to the baseline (from 5410 to 398; p ¼ 0,008); e) significant reduction of cumulative HF hospitalization days in the postprocedure year (10 days) compared to the pre-implantation year (280 days; p ¼ 0.023) was observed. Conclusions: In patients with refractory HF and MR 3þ, MitraClip implantation resulted in acute and persistent clinical benefit and net reduction of HF re-hospitalization. (J Interven Cardiol 2015;28:61–68)
Introduction Mitral regurgitation (MR), regardless of its etiology, is associated with a poor prognosis in patients with systolic heart failure (HF).1 Surgical mitral valve repair/replacement is the gold standard for treatment of symptomatic patients with severe MR on the basis of current guidelines.2,3 However, most of these patients have prohibitively high surgical risk due to left ventricular systolic dysfunction or significant comor-
Disclosure statement: The authors have no conflicts of interest to disclose. Address for reprints: Salvatore Curello, M.D., Piazzale Spedali Civili, 1 – Spedali Civili –25100– Brescia, Italy. Fax: þ39030399582; e-mail: [email protected]
Vol. 28, No. 1, 2015
bidities.4 The MitraClip technique appears to be safe, with high procedural success rate and low procedural mortality, and effectiveness with significant improvement of functional outcomes, such as New York Heart Association (NYHA) class, 6-minutes-walk distance and quality of life scores, either in low and high patients.5,6 Some studies have shown a beneficial role of such procedure also in patients with functional MR and severe or end-stage HF.7,8 In addition, few case reports described the use of MitraClip therapy as rescue therapy in terminally ill patients whose clinical course would otherwise unlikely be changed.9–11 This tends to support a possible role of MitraClip in patients who have no other therapeutic options in presence of elevated hospitalization costs. The aim of this study was to assess the acute-, early-, mid- and long-term
Journal of Interventional Cardiology
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ADAMO, ET AL.
outcomes of patients with moderate to severe or severe MR and refractory HF who underwent MitraClip implantation at our institution.
Materials And Methods Study Population. Patient population comprises all patients undergoing MitraClip procedure with refractory HF, defined as (1) dependence on diuretics and/or inotropic drugs infusion and/or intraaortic balloon pump (IABP) (group A) or (2) labile hemodynamic balance (group B). Dependence on diuretic and/or inotropic drugs continuous infusion and/or IABP was defined as inability to wean from these supports without worsening of HF symptoms and/or oligo-anuria and/ or symptomatic hypotension. Labile hemodynamic balance was defined as recent (50 days prior to hospital admission for MitraClip implantation) and frequent or prolonged (at least 20 days in total) hospitalization due to acute HF, despite optimal medical oral therapy, requiring intravenous diuretics. Drugs used were: furosemide as diuretic and dopamine, dobutamine and/or enoximone as inotropic. Preimplantation time, for group A, was defined as length (days) of in-hospital stay on refractory HF between admission and MitraClip implantation. Recent-hospitalization-time, for group B, was defined as number of days of HF hospitalization during the last 50 days before the admission for MitraClip implantation. All patients were on optimal medical therapy, included cardiac resynchronization therapy (CRT) if indicated, according to current guidelines on management of HF.12 They were evaluated by a multidisciplinary team of HF specialist, interventional cardiologist, echocardiographer, cardiac surgeon and anesthesiologist and after receiving a complete oral and written explanation of the issues surrounding MitraClip implantation, they gave a written consent for the procedure and data collection. Echocardiographic Measurements. Prior to MitraClip implantation, all patients underwent transthoracic (TTE) and transesophageal echocardiography (TEE) to quantify mitral valve regurgitation and to judge morphologic suitability for MitraClip implantation. At discharge and during the follow up, only TTE was performed. The severity of MR was classified into 4 grades using semiquantitative manner with color Doppler (color flow mapping) and quantified by the
62
vena contracta width and the proximal isovelocity surface area method according to American Association of Echocardiography recommendations.13 Other echocardiographic parameters included: left ventricular ejection fraction (LVEF), left ventricular enddiastolic diameter (LVEDD), left atrium diameter (LAD) and systolic pulmonary artery pressure (SPAP). LVEF was assessed using biplane and Simpson’s method, LVEDD and LAD by M-Mode method and SPAP using tricuspid regurgitation flow velocity. MitraClip Procedure. The MitraClip System procedure has been previously described.14,15 Briefly, MitraClip is a catheter-based system consisting of a steerable 24 Fr guide catheter and a clip delivery system. The clip device system is delivered to the left atrium (LA) via a transeptal puncture advanced into the left ventricle (LV) and then retracted during systole, grasping the mitral valve leaflets. This results in permanent leaflet coaptation and a double orifice valve that is similar in effect to the surgical Alfieri technique. If necessary, the device can be reopened, the leaflets released and the MitraClip device repositioned. A second clip device was placed at operator discretion to obtain additional MR reduction. The procedure was performed under general anesthesia and both fluoroscopic and TEE (Two and three-dimensional) guidance. Procedural success was defined as implantation of at least one clip resulting in a MR 2þ. Acute Outcomes and Follow Up. Weaning-time, for group A, was defined as the interval (days) between MitraClip implantation and weaning from pharmacological and/or mechanical supports described above. For all 2 groups, discharge-time was defined as the interval (days) between MitraClip implantation and discharge from hospital. Back-at-home time was defined as summary of discharge time and the length (days) of rehabilitation period. Rehospitalization time, for group B, was defined as the number of days of HF hospitalization during the 50 days after back at home. TEE and NYHA functional class assessment were performed at 30 days, 6 months and 1 year and then yearly thereafter. Assessment of HF hospitalization at 1 year from index procedure included the number of days of hospitalization for HF during the year after back at home post MitraClip implantation, hence excluding back at home time. HF hospitalization at 1 year was compared to days of hospitalization due to HF in the preimplantation year excluding days of hospitalization before MitraClip implantation, from admission to index procedure.
Journal of Interventional Cardiology
Vol. 28, No. 1, 2015
MITRACLIP IN REFRACTORY HEART FAILURE Table 1. Baseline Characteristics Group A
Age (years)
Gender
LES
ESII
STS score
STSc
NYHA class
Etiology
MR degree
SPAP (mmHg)
LAD (mm)
LVEDD (mm)
LVEF (%)
1 2 3 4 5 6 7 8
77 78 76 82 72 74 73 71
M F M F M F M M
60.6 28 8.4 25.8 22.8 14.5 35.5 9.2
30.1 15.7 10.4 10.6 16.3 9.8 21.,4 4.7
10.3 7.1 7.0 17.8 4.8 4.0 9.9 1.9
49.3 42.3 34.4 51.0 29.9 28.4 59.7 17.4
4 4 4 4 4 4 4 4
FIS FIS ORG ORG FIS FIS FIS FID
3 4 4 4 4 4 4 4
70 45 40 46 40 46 55 48
45 42 38 44 55 42 55 60
64 62 58 70 84 52 75 78
30 32 50 65 19 38 7 18
Group B
Age (years)
Gender
LES
ESII
STS score
STSc
NYHA class
Etiology
MR degree
SPAP (mmHg)
LAD (mm)
LVEDD (mm)
LVEF (%)
9 10 11 12 13 14 15 16
41 45 70 72 70 44 84 75
M M M M M M F M
4.4 8.9 48.9 18.9 7 13.9 25.2 26.5
3.5 5.6 25.3 4.2 7.4 2.9 12.1 29.8
0.6 1.4 12.6 1.9 1.6 1.2 7.7 9.7
13.7 28.5 57.7 17.5 17.0 24.2 34.3 51.7
4 4 4 3 4 4 4 4
FIS FID FIS FID FIS FIS FID FIS
4 4 4 4 4 4 4 4
55 70 60 68 55 70 50 55
49 45 55 50 57 57 40 49
70 71 68 70 83 68 75 76
15 20 35 33 21 25 27 25
ESII, Euroscore II; FID, functional idiopathic; FIS, functional ischemic; LAD, left atrium diameter; LES, Logistic Euroscore; LVEDD, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction; MR, mitral regurgitation; ORG, organic; SPAP, systolic pulmonary artery pressure; STS, Society of thoracic surgeons score of mortality; STSc, STS mortality and morbility
Statistical Analysis. Continuous variables are reported as mean standard deviation (SD). HF hospitalizations in the pre and postimplantation year are reported as amount of days. All continuous parameters are compared using the t-test. Categorical data were expressed as counts and percentage and differences between groups were examined with Chi Square test. The cumulative survival rate at 1 year was estimated using the Kaplan–Meier method. For all analysis, a 2 slides P value
STRUCTURAL HEART DISEASE Effectiveness of MitraClip Therapy in Patients with Refractory Heart Failure MARIANNA ADAMO, M.D., 1 MARCO BARBANTI, M.D., 2 SALVATORE CURELLO, M.D., 1 CLAUDIA FIORINA, M.D., 1 ERMANNA CHIARI, M.D., 1 GIULIANO CHIZZOLA, M.D., 1 DAVIDE CAPODANNO, M.D., P H .D., 2 CORRADO TAMBURINO, M.D., P H .D., 2 MARCO METRA, M.D., 1 and FEDERICA ETTORI, M.D. 1 From the 1Spedali Civili, Brescia, Italy; and 2Ferrarotto Hospital, Catania, Italy
Objectives: To assess outcomes for MitraClip therapy in patients with refractory heart failure (HF) and mitral regurgitation (MR) 3þ. Background: The beneficial role of Mitraclip also in patients with severe HF has been reported. Methods: Out of 45 patients undergoing MitraClip implantation at our institute, 16 were on refractory HF defined as diuretics and/or inotropics infusion and/or IABP dependence (group A) or labile haemodynamic balance (group B). Results: Patients were aged 69 13 years and 75% were males. Group A (8 patients) had a mean hospitalization length before MitraClip procedure of 5333 days. Group B (8 patients) had a mean rate of hospitalization, in the last 50 days before procedure, of 254 days. Acute procedural success was observed in 94% of patients. All but one patients of group A were quickly weaned from pharmacologic and/or mechanical supports within 5 3 days from procedure and discharged at 2010 days. All patients of group B were discharged after 108 days from MitraClip. At 1 year: a) cumulative survival rate was 78%; b) all patients were in NYHA functional class II; c) residual MR 2 was observed in 90%; d) systolic pulmonary arterial pressure was significantly reduced compared to the baseline (from 5410 to 398; p ¼ 0,008); e) significant reduction of cumulative HF hospitalization days in the postprocedure year (10 days) compared to the pre-implantation year (280 days; p ¼ 0.023) was observed. Conclusions: In patients with refractory HF and MR 3þ, MitraClip implantation resulted in acute and persistent clinical benefit and net reduction of HF re-hospitalization. (J Interven Cardiol 2015;28:61–68)
Introduction Mitral regurgitation (MR), regardless of its etiology, is associated with a poor prognosis in patients with systolic heart failure (HF).1 Surgical mitral valve repair/replacement is the gold standard for treatment of symptomatic patients with severe MR on the basis of current guidelines.2,3 However, most of these patients have prohibitively high surgical risk due to left ventricular systolic dysfunction or significant comor-
Disclosure statement: The authors have no conflicts of interest to disclose. Address for reprints: Salvatore Curello, M.D., Piazzale Spedali Civili, 1 – Spedali Civili –25100– Brescia, Italy. Fax: þ39030399582; e-mail: [email protected]
Vol. 28, No. 1, 2015
bidities.4 The MitraClip technique appears to be safe, with high procedural success rate and low procedural mortality, and effectiveness with significant improvement of functional outcomes, such as New York Heart Association (NYHA) class, 6-minutes-walk distance and quality of life scores, either in low and high patients.5,6 Some studies have shown a beneficial role of such procedure also in patients with functional MR and severe or end-stage HF.7,8 In addition, few case reports described the use of MitraClip therapy as rescue therapy in terminally ill patients whose clinical course would otherwise unlikely be changed.9–11 This tends to support a possible role of MitraClip in patients who have no other therapeutic options in presence of elevated hospitalization costs. The aim of this study was to assess the acute-, early-, mid- and long-term
Journal of Interventional Cardiology
61
ADAMO, ET AL.
outcomes of patients with moderate to severe or severe MR and refractory HF who underwent MitraClip implantation at our institution.
Materials And Methods Study Population. Patient population comprises all patients undergoing MitraClip procedure with refractory HF, defined as (1) dependence on diuretics and/or inotropic drugs infusion and/or intraaortic balloon pump (IABP) (group A) or (2) labile hemodynamic balance (group B). Dependence on diuretic and/or inotropic drugs continuous infusion and/or IABP was defined as inability to wean from these supports without worsening of HF symptoms and/or oligo-anuria and/ or symptomatic hypotension. Labile hemodynamic balance was defined as recent (50 days prior to hospital admission for MitraClip implantation) and frequent or prolonged (at least 20 days in total) hospitalization due to acute HF, despite optimal medical oral therapy, requiring intravenous diuretics. Drugs used were: furosemide as diuretic and dopamine, dobutamine and/or enoximone as inotropic. Preimplantation time, for group A, was defined as length (days) of in-hospital stay on refractory HF between admission and MitraClip implantation. Recent-hospitalization-time, for group B, was defined as number of days of HF hospitalization during the last 50 days before the admission for MitraClip implantation. All patients were on optimal medical therapy, included cardiac resynchronization therapy (CRT) if indicated, according to current guidelines on management of HF.12 They were evaluated by a multidisciplinary team of HF specialist, interventional cardiologist, echocardiographer, cardiac surgeon and anesthesiologist and after receiving a complete oral and written explanation of the issues surrounding MitraClip implantation, they gave a written consent for the procedure and data collection. Echocardiographic Measurements. Prior to MitraClip implantation, all patients underwent transthoracic (TTE) and transesophageal echocardiography (TEE) to quantify mitral valve regurgitation and to judge morphologic suitability for MitraClip implantation. At discharge and during the follow up, only TTE was performed. The severity of MR was classified into 4 grades using semiquantitative manner with color Doppler (color flow mapping) and quantified by the
62
vena contracta width and the proximal isovelocity surface area method according to American Association of Echocardiography recommendations.13 Other echocardiographic parameters included: left ventricular ejection fraction (LVEF), left ventricular enddiastolic diameter (LVEDD), left atrium diameter (LAD) and systolic pulmonary artery pressure (SPAP). LVEF was assessed using biplane and Simpson’s method, LVEDD and LAD by M-Mode method and SPAP using tricuspid regurgitation flow velocity. MitraClip Procedure. The MitraClip System procedure has been previously described.14,15 Briefly, MitraClip is a catheter-based system consisting of a steerable 24 Fr guide catheter and a clip delivery system. The clip device system is delivered to the left atrium (LA) via a transeptal puncture advanced into the left ventricle (LV) and then retracted during systole, grasping the mitral valve leaflets. This results in permanent leaflet coaptation and a double orifice valve that is similar in effect to the surgical Alfieri technique. If necessary, the device can be reopened, the leaflets released and the MitraClip device repositioned. A second clip device was placed at operator discretion to obtain additional MR reduction. The procedure was performed under general anesthesia and both fluoroscopic and TEE (Two and three-dimensional) guidance. Procedural success was defined as implantation of at least one clip resulting in a MR 2þ. Acute Outcomes and Follow Up. Weaning-time, for group A, was defined as the interval (days) between MitraClip implantation and weaning from pharmacological and/or mechanical supports described above. For all 2 groups, discharge-time was defined as the interval (days) between MitraClip implantation and discharge from hospital. Back-at-home time was defined as summary of discharge time and the length (days) of rehabilitation period. Rehospitalization time, for group B, was defined as the number of days of HF hospitalization during the 50 days after back at home. TEE and NYHA functional class assessment were performed at 30 days, 6 months and 1 year and then yearly thereafter. Assessment of HF hospitalization at 1 year from index procedure included the number of days of hospitalization for HF during the year after back at home post MitraClip implantation, hence excluding back at home time. HF hospitalization at 1 year was compared to days of hospitalization due to HF in the preimplantation year excluding days of hospitalization before MitraClip implantation, from admission to index procedure.
Journal of Interventional Cardiology
Vol. 28, No. 1, 2015
MITRACLIP IN REFRACTORY HEART FAILURE Table 1. Baseline Characteristics Group A
Age (years)
Gender
LES
ESII
STS score
STSc
NYHA class
Etiology
MR degree
SPAP (mmHg)
LAD (mm)
LVEDD (mm)
LVEF (%)
1 2 3 4 5 6 7 8
77 78 76 82 72 74 73 71
M F M F M F M M
60.6 28 8.4 25.8 22.8 14.5 35.5 9.2
30.1 15.7 10.4 10.6 16.3 9.8 21.,4 4.7
10.3 7.1 7.0 17.8 4.8 4.0 9.9 1.9
49.3 42.3 34.4 51.0 29.9 28.4 59.7 17.4
4 4 4 4 4 4 4 4
FIS FIS ORG ORG FIS FIS FIS FID
3 4 4 4 4 4 4 4
70 45 40 46 40 46 55 48
45 42 38 44 55 42 55 60
64 62 58 70 84 52 75 78
30 32 50 65 19 38 7 18
Group B
Age (years)
Gender
LES
ESII
STS score
STSc
NYHA class
Etiology
MR degree
SPAP (mmHg)
LAD (mm)
LVEDD (mm)
LVEF (%)
9 10 11 12 13 14 15 16
41 45 70 72 70 44 84 75
M M M M M M F M
4.4 8.9 48.9 18.9 7 13.9 25.2 26.5
3.5 5.6 25.3 4.2 7.4 2.9 12.1 29.8
0.6 1.4 12.6 1.9 1.6 1.2 7.7 9.7
13.7 28.5 57.7 17.5 17.0 24.2 34.3 51.7
4 4 4 3 4 4 4 4
FIS FID FIS FID FIS FIS FID FIS
4 4 4 4 4 4 4 4
55 70 60 68 55 70 50 55
49 45 55 50 57 57 40 49
70 71 68 70 83 68 75 76
15 20 35 33 21 25 27 25
ESII, Euroscore II; FID, functional idiopathic; FIS, functional ischemic; LAD, left atrium diameter; LES, Logistic Euroscore; LVEDD, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction; MR, mitral regurgitation; ORG, organic; SPAP, systolic pulmonary artery pressure; STS, Society of thoracic surgeons score of mortality; STSc, STS mortality and morbility
Statistical Analysis. Continuous variables are reported as mean standard deviation (SD). HF hospitalizations in the pre and postimplantation year are reported as amount of days. All continuous parameters are compared using the t-test. Categorical data were expressed as counts and percentage and differences between groups were examined with Chi Square test. The cumulative survival rate at 1 year was estimated using the Kaplan–Meier method. For all analysis, a 2 slides P value
