Canadian Journal of Cardiology 29 (2013) 1422e1428
Clinical Research
Percutaneous Paravalvular Leak Reduction: Procedural and Long-term Clinical Outcomes Stephane Noble, MD,a,b E. Marc Jolicoeur, MD, MSc, MHS,a Arsène Basmadjian, MD, MSc,a Sylvie Levesque, MSc,a Anna Nozza, MSc,a Jeannot Potvin, MD,a Jacques Crepeau, MD,a and Reda Ibrahim, MDa a
From the Department of Medicine, Montreal Heart Institute, Universite de Montre al, Montreal, Que bec, Canada b
From the Department of Medical Specialties, Cardiology Division, Universite de Genève, Geneva, Switzerland
ABSTRACT
RESUM E
Background: Significant paravalvular leak (PVL) after prosthetic replacement can result in hemolysis and/or congestive heart failure (CHF). Percutaneous PVL reduction (PPVR) represents an alternative to repeat surgery for a selected population. The purpose of this study was to assess the procedural and long-term clinical efficacy of percutaneous PPVR and its effect on survival free of rehospitalization for CHF, surgical reintervention, and death. Methods: We analyzed a cohort of 56 consecutive patients who underwent 61 PPVRs in our institution between June 2001 and December 2010. Procedural success was defined as a reduction in regurgitation severity free from procedural complications. Patients were followed-up for vital status, clinical events, and symptoms. Results: Patients were aged 65 11 years, with an average logistic EuroSCORE of 19 14%. Indications for PPVR included CHF (61%), hemolysis (9%), or both (30%), caused by mitral (n ¼ 44) or aortic (n ¼ 12) PVL. Procedural success was achieved in 75% of cases. Three major complications, including 2 deaths, occurred during the initial 30-day follow-up in the 42 patients who were treated with a device. After adjusting for the logistic EuroSCORE, prosthesis type (mitral vs aortic), and time interval since the last valve surgery,
Introduction : Une fuite paravalvulaire (FPV) significative après un tique peut entraîner une he molyse de l’insuffisremplacement prothe duction percutane e ance cardiaque congestive (ICC), ou les deux. La re sente une alternative à la reprise chirurgicale de la FPV (RPFPV) repre lectionne s. Le but de cette e tude e tait d’e valuer le pour des patients se clinique à long terme de succès technique de l’intervention et l’efficacite hospitalisation pour ICC, la RPFPV et son effet sur la survie sans re intervention chirurgicale et mortalite . re thodes : Nous avons analyse une cohorte de 56 patients conse cutifs Me tablissement entre juin 2001 et qui ont subi 61 RPFPV dans notre e cembre 2010. Le succès de l’intervention a e te de fini par une dimide de re gurgitation en l’absence de complications lie es à nution du degre dure. Les patients ont eu un suivi de leur statut vital, des la proce ve nements cliniques et de leurs symptômes. e sultats : Les patients e taient âge s de 65 11 ans et avaient un Re EuroSCORE logistique moyen de 19 14 %. Les indications de RPFPV molyse (9 %) ou les deux (30 %), cause es incluaient l’ICC (61 %), l’he par la FPV mitrale (n ¼ 44) ou aortique (n ¼ 12). Le succès de l’in te atteint dans 75 % des cas. Trois (3) complications tervention a e cès, sont apparues durant le suivi initial de majeures, incluant 2 de
Paravalvular leak (PVL) after surgical mitral or aortic valve replacement is the most common cause of nonstructural prosthetic heart valve dysfunction, and it is usually associated with extensive annular calcification, tissue friability, or endocarditis.1 Immediate postoperative PVL is present in 6% to 18% of patients with aortic and in 23% to 32% with mitral valve replacement.2,3 Clinical repercussions of PVL vary from absence of symptoms to congestive heart failure (CHF) and/or significant hemolytic anemia requiring multiple transfusions.4
It is estimated that 3% to 12% of patients undergoing mitral or aortic valve replacement will develop clinically relevant PVL.5 Traditionally, repeat open heart surgery has been the only corrective option for PVL, despite being associated with mortality rates ranging from 4% to 13%.1,6-8 There is also an increased risk of residual or recurrent PVL after repeat surgery because the initial underlying tissue fragility usually persists.1 Percutaneous PVL reduction (PPVR), a less invasive technique, has emerged as an alternative to medical therapy and repeat surgery.9-15 The reported experience with PPVR to date is limited and long-term follow-up is sparse.9,13-18 The present study sought to assess the procedural and long-term clinical efficacy (ie, survival free of rehospitalization for CHF, surgical reintervention, and death) and safety of PPVR in patients with symptomatic PVL anatomically suitable for a percutaneous approach.
Received for publication April 23, 2013. Accepted July 29, 2013. Corresponding author: Dr Reda Ibrahim, Montreal Heart Institute, 5000 Belanger St E, Montreal, Quebec H1T 1C8, Canada. Tel.: þ1-514-376-3330 3800; fax: þ1-514-593-2158. E-mail: [email protected] See page 1427 for disclosure information.
0828-282X/$ - see front matter Ó 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.cjca.2013.07.800
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a successful PPVR was associated with a better survival free of rehospitalisation for CHF, need for surgical reintervention, and death compared with patients with a failed PPVR. (hazard ratio ¼ 0.34; 95% confidence interval, 0.17-0.71). Conclusions: PPVR is associated with a reasonable rate of procedural success and favourable cardiovascular outcomes, and represents an appropriate option when technically possible.
te implante . 30 jours chez les 42 patients chez qui un dispositif a e Après l’ajustement de l’EuroSCORE logistique, du type de prothèse (mitrale vs aortique) et de l’intervalle de temps depuis la dernière te associe à une meilchirurgie valvulaire, le succès de la RPFPV a e hospitalisation pour ICC, ne cessite de leure survie sans re intervention chirurgicale et mortalite comparativement aux patients re chec de la RPFPV (rapport de risque ¼ 0,34; intervalle de ayant eu un e confiance à 95 %, 0,17-0,71). e à un taux raisonnable de succès Conclusions : La RPFPV est associe sultats cardiovasculaires favorables, et interventionnel et à des re sente une option approprie e lorsqu’elle est techniquement repre possible.
Methods
prosthesis, diagnosed using Doppler echocardiography. Preprocedural transthoracic and transesophageal echocardiography (TEE) were performed to describe the size, severity, shape, and precise location of the PVL. Prosthetic regurgitation was assessed according to published practice guidelines.19 Severity of regurgitation assessed using echocardiography before publication of theses guidelines used an integrative approach and criteria similar to those later published in the guidelines based on structural 2-dimensional and Doppler data.20 Prosthetic valve function was also evaluated using the American Society of Echocardiography guidelines.19,20 The location of the leak was described according to the clock face approach adapted from the operating room to the catheterization laboratory.21 Procedural complications included death, stroke, tamponade, device embolization, impaired prosthetic function, vascular access site bleeding requiring intervention, and any untoward medical event requiring urgent conversion to open chest surgery occurring within the first 48 hours after the procedure. Procedural success was defined as a device implantation resulting in a PVL reduction of 1 grade, quantified using echocardiographic methods and free of procedural complications assessed using TEE and fluoroscopy. Clinical success was defined as NYHA functional class < III and/or no significant hemolysis, and survival free of reintervention or rehospitalization for CHF. CHF was defined as symptoms corresponding to NYHA functional class grade III. Significant hemolysis was defined as hemolytic anemia requiring > 2 units of blood transfusion within 90 days without any objective bleeding.
Patient population Between June 2001 and December 2010, 56 consecutive patients underwent 61 percutaneous procedures of aortic or mitral PVL reduction in our institution. Patients had to be symptomatic (dyspnea, New York Heart Association [NYHA] 3 despite optimal medical therapy and/or clinically significant hemolytic anemia requiring transfusions) and at high risk for repeat surgery or without surgical options. PPVR was attempted provided that an echocardiographic assessment revealed a PVL anatomically suitable for percutaneous reduction. Patients with active endocarditis or an unstable valve (large dehiscence involving > 40% of the valve circumference or obvious prosthesis rocking) were not considered candidates for the procedure. Data collection and follow-up Baseline demographic characteristics, medical history, cardiac catheterization data, and in-hospital outcomes were collected from medical charts and procedural reports. Risk stratification for surgical reintervention was performed using the logistic EuroSCORE, the Society of Thoracic Surgeons (STS) score, and the Parsonnet score. The logistic EuroSCORE does not take into account the number of previous reinterventions, whereas the STS score and the Parsonnet score do take into account the precise number of repeat surgeries in the risk calculation. Follow-up information and vital status were collected from medical charts, dedicated clinical visits, and by a mailed questionnaire or phone calls when required. Collected information included vital status, need for percutaneous or surgical reintervention related to PVL, NYHA functional class, need for red blood cell transfusion, and rehospitalization for CHF. The national death index was used to determine vital status for nonresponders. Follow-up was 100% complete for the composite outcomes of survival free of rehospitalization for CHF, surgical reintervention, and death at 1 year. All patients were informed of the procedural risks and options, and signed the informed consent for the intervention. The present study was approved by the Institutional Review Board. Clinical definitions PVL corresponds to a regurgitant jet located between the native tissue around the valve and the outer margin of the
PPVR reduction technique Most procedures were performed using general anaesthesia with fluoroscopic and TEE guidance. Antibiotic prophylaxis was administered 30 minutes before the procedure. Unfractioned heparin was administered to maintain an activated clotting time greater than 250 seconds. Briefly, aortic PVLs were performed using a retrograde (retroaortic) approach whereas mitral PVLs were treated using a transseptal antegrade technique. No transapical approach was attempted. Various Amplatzer occluder devices (St Jude Medical, Plymouth, MN) were used during the study period. We initially performed PPVR using exclusively the Amplatzer Duct I (PDA) Occluder device. Between 2005 and 2008, we switched to the Amplatzer Muscular Ventricular Septal Defect (VSD) Occluder device. Since 2008, we have been using either the
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Amplatzer Muscular VSD Occluder device or the Amplatzer Vascular Plug (AVP) III according to the anatomy of the defect. The oval design of the AVP III device makes it the preferred device for the common crescent-shaped leaks whereas the Amplatzer VSD occluder is preferred for circular defects. Before final device release, the absence of interference with the valve prosthesis was evaluated using fluoroscopy and echocardiography. Statistical analysis and modelling of outcomes Continuous variables are described using means SD or medians with interquartile range as appropriate and compared using Wilcoxon rank sum tests. Categorical variables are presented as numbers (percentages), and compared using either c2 or Fisher’s exact tests. Kaplan-Meier methods were used to illustrate the survival free of rehospitalization for CHF, surgical reintervention, and death for patients who did and did not undergo a successful PPVR (primary objective and end point). To adjust for known or expected confounding variables, a multivariable Cox proportional hazards regression was developed. Candidate predictor variables thought to be clinically important were prespecified and included: (1) successful vs failed PPVR; (2) the logistic EuroSCORE; (3) mitral vs aortic PPVR; and (4) time interval between the last valve replacement and the PPVR. The baseline model’s discrimination was evaluated using the c-index.22 No data imputation was performed. Statistical significance was determined at the 2-sided a ¼ 0.05 level. Data analyses were performed using the SAS software package (version 9.2, SAS Institute, Cary, NC). Results
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(Fig. 1). The procedural success rate was 40% (2 of 5 patients) when significant hemolysis was the only indication for PPVR, and it was 78.4% (40 of 51 patients) when the indication involved heart failure with or without hemolysis. Five patients underwent a second percutaneous intervention because of initial failure (n ¼ 1 at 59 days) and persistent or additional symptomatic leaks (n ¼ 4 at 20, 48, 113, and 321 days). For the 61 procedures, the rate of success was 75.4% (46 of 61). Reasons for failed device implantation are listed in Table 2. In 5 patients (9.8%), 2 occluder devices were required to achieve an appropriate PVL reduction. No complications were caused by transseptal puncture. Two patients had transient prosthetic leaflet impingement during attempted implantation precluding the release of any device. Three major periprocedural complications were recorded. In 1 patient, at day 3 the PDA occluder embolized from the mitral position into the aortic bileaflet mechanical prosthesis resulting in rapid death. A second patient developed an early severe hemolytic syndrome, which led to an urgent successful surgical removal of the muscular ventricular septal defect device followed by a surgical repair at day 5 after implantation. A third patient died from renal bleeding 12 days after the implantation without any clear explanation. Mortality rate at 30 days was 8.9% (n ¼ 5) overall, 4.8% (2 of 42) in the group of successful PPVR, and 21.4% (3 of 14) in the group of procedural failure. In the latter group, 1 patient died of a stroke (day 20) and 2 of CHF while in palliative care. At discharge, 81.0% (34 of 42) of the patients with a procedural success were in functional class I and II, whereas 88.1% of them were in functional class > III before the intervention (37 of 42). Hemolysis before and after the procedure is described in Supplemental Table S2 for patients who had a device implanted.
Baseline characteristics From June 2001 to December 2010, 56 consecutive patients underwent 61 PPVRs (Fig. 1). Baseline characteristics are presented in Supplemental Table S1. All patients were symptomatic with heart failure and/or hemolytic anemia requiring repetitive transfusions. Heart failure alone or associated with hemolysis was the most common indication for PPVR (91%). PVL localization was more often mitral (78.6%) than aortic (21.4%). For mitral patients, the most frequent PVL locations were lateral and septal in 21 (47.8%), and 16 patients (36.4%), respectively. On average, patients had undergone 2.4 1.3 thoracotomies (up to 7) with a median time interval between the last surgery and the PPVR of 80.7 (range, 21.9-125.6) months. Significant comorbidities were present in the study population as shown by the elevated logistic EuroSCORE, STS, and Parsonnet scores. Procedural characteristics are listed in Table 1. Initially 1 of the 2 different operators performed procedures using local anaesthesia without TEE guidance (14.8%), corresponding respectively to 38.5% and 10.5% of the aortic and mitral procedures. Procedural in-hospital complications and 30-day outcomes Table 1 also lists the procedural results. Procedural success was achieved in 42 patients in the overall cohort (75.0%)
Mid- to long-term outcomes Patients were followed for an average of 29 27 months and a median of 30 months, providing a total of 156.7 patient-years of information available for the survival analysis. Follow-up information beyond 1 year was available for all patients. Supplemental Table S3 compares the incidence of rehospitalization for CHF, surgical reintervention, and death between patients who did and did not undergo a successful PPVR. The unadjusted survival was statistically nonsignificant (50% vs 57%; hazard ratio, 0.60; 95% confidence interval, 0.27-1.31) between patients with successful and failed PPVR, respectively. During the follow-up period, 21 of 42 (50%) patients with a successful PPVR died and 62% (13 of 21) of these deaths occurred after the first year. Clinical success at 3 months and 1 year were respectively achieved in 69.0% (29 of 42) and 54.8% (23 of 42) of the patients with an initial procedural success. Seven patients (16.7%) required repeat valve surgery despite a successful initial PPVR (at day 5, 32, 148, 229, 435, 757, and 1022). Indications for the surgical reintervention were significant hemolysis in 3 patients (at day 5, 148, and 757) and progression of PVL in 4 patients. The patient who required a surgical reintervention at 32 days had an initial PVL reduction from grade IV to II, but he reported no symptomatic improvement at 30 days and the leak had
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Figure 1. Patient flow chart. PPVR, percutaneous paravalvular leak reduction.
progressed on both sides of the 6-mm VSD device according to echocardiography performed after discharge. The aetiology for this further degradation of the valve attachment was the underlying tissue and suture fragility because of a nondiagnosed culture-negative endocarditis. Out of the 14 patients with initial failed PPVR, 6 patients (43%) required a repeat valve surgery, all of which were performed in the following year. Table 1. Procedural characteristics
Characteristic General anaesthesia TEE guidance Retrograde approach Transseptal approach Transapical approach Procedures with device implanted Device implanted, total n Procedures with 2 devices Occluder devices used PDA occluder mVSD occluder Vascular plug III Two different devices Device not implanted Procedural time, min Fluoroscopic time, min Contrast used (range), mL Residual regurgitation grade 2 Residual regurgitation grade 3 Procedural success with residual regurgitation 2
Aortic and mitral (n ¼ 56) 47 (83.9) 47 (83.9)
42 (75.0) 49 5 (8.9)
Aortic (n ¼ 12)
Mitral (n ¼ 44)
7 (58.3) 7 (58.3) 12 (100) 0 0 7 (58.3) 9 2 (16.7)
40 (90.1) 40 (90.1) 0 44 (100) 0 35 (79.5) 40 3 (6.8)
14 (25.0) 5 (41.7) 22 (39.3) 2 (16.7) 5 (8.9) 0 1 (1.8) 0 14 (25.0) 5 (41.7) 127 46 113 49 50 24 42 24 34 (0-300) 76 (0-300) 22 (39.3) 5 (41.7) 6 (10.7) 1 (8.3) 36 (64.3) 6 (50)
9 (20.4) 20 (45.4) 5 (11.4) 1 (2.3) 9 (20.4) 131 45 53 24 21 (0-255) 17 (38.6) 5 (11.4) 30 (68.2)
Data are presented as mean SD or n (%), unless otherwise indicated. mVSD, muscular ventricular septal defect; PDA, patent ductus arteriosus; TEE, transesophageal echocardiography.
During the follow-up period, 15 patients (35.7%) with successful PPVR were readmitted for symptoms of worsening heart failure (n ¼ 13) and/or significant hemolysis (n ¼ 2). Association between a successful PPVR reduction and long-term outcomes After multivariable adjustment, a successful PPVR was strongly associated with a better survival free of rehospitalization for CHF, surgical reintervention, and death (hazard ratio, 0.34; 95% confidence interval, 0.17-0.71) (Fig. 2). The other candidate predictors (logistic EuroSCORE, left ventricular ejection fraction, and the time interval between the last surgery and the PVL reduction) were not associated with the primary end point (Table 3). We performed sensitivity analyses to assess the robustness of our findings in varying clinical scenarios. Indeed, a successful PPVR remained associated with improved outcomes even when the definition of Table 2. Reasons for failed device implantation Reason Inability to cross with guide wire Inability to cross with catheter Instability of occluder device Inability to size the defecty Prosthetic leaflet impingement
Aortic and mitral (n ¼ 15)* 9 2 1 1 2
(60.0)* (13.3) (6.6) (6.6) (13.3)
Aortic (n ¼ 6)
Mitral (n ¼ 9)
4 (66.6)* 0 0 1 (16.6) 1 (16.6)
5 (55.5) 2 (22.2) 1 (11.1) 0 1 (11.1)
Data are presented as n (%). PVL, paravalvular leak. * Fourteen patients had a failed device implantation including a patient with an aortic PVL having 2 failed procedures caused by the inability to cross the defect with the guide wire. y Before the 3-dimensional era, size and shape of the PVL could be difficult to assess.
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procedural success was modified to include only patients with a final leak of less than Grade 3, or when the study end point was modified to include the need for repeated percutaneous PPVR (Table 3). In all cases the c-indices associated with the models remained greater than 0.80, therefore indicating a good model discrimination. Discussion Until recently, surgical reintervention was the only option to treat PVL. Because of pioneer experience from different centres with encouraging results, PPVR has emerged as an attractive alternative. Our study demonstrates that a successful PPVR compared with a failed procedure is associated with better cardiovascular outcomes, mainly by reducing the number of rehospitalizations for CHF and the need for further reintervention. Considering the relatively high procedural success rate in the hands of a trained interventionalist, PPVR can be considered as a reasonable option in patients at high risk for surgical reintervention. Our cohort of mitral and aortic PPVR represents one of the largest series reported to date permitting the investigation of the feasibility, safety, and short- and long-term clinical outcome of PPVR. To the best of our knowledge, this represents the series with the longest follow-up to date. Procedural success was achieved in 75% and clinical success at 3 months was 69% after a successful device implantation. Our results are concordant with the 3 largest series published to date,14,16,23,24 which show successful implantation rates between 63% and 91% with a concomitant clinical improvement in 51%-89% of patients when a device could be implanted. Despite the very high-risk profiled46%
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of our patients had 3 previous cardiac surgeriesdthe procedural complication rate seems acceptable with only 1 device-related death and 1 early urgent surgical reintervention because of severe hemolysis, induced by the device. Over the years, the procedure has greatly evolved in relation to improvements in imaging, material, and catheterization techniques.24 This has led to an increase in procedural success rates and safety and also a decrease in procedural time. The availability of a steerable transseptal sheath (ie, Agilis catheter, St Jude Medical) has undoubtedly facilitated the mitral PVL approach, particularly when the leak is in a septal location. A major breakthrough was also the availability of hydrophilic and braided delivery sheaths (TorqVue from St Jude Medical, Flexor/Shuttle from Cook, and Destination from Terumo) to cross serpiginous and calcified leaks. Nowadays, 3-dimensional echocardiographyd not available in this seriesdprovides great help to assess the size and shape of the defect and the distance between the defect and the valve prosthesis to select the appropriate device size and type. The inability to size the defect in 1 patient would have probably been solved with the use of 3-dimensional echocardiography. Since the fatal embolization of a PDA device in our series, we are reluctant to use this device, which has only 1 retention disk and a higher risk of embolization.4,25 We believe that 2-disk devices, such as the muscular VSD device, the AVP III device (available in Europe and Canada since 2008 and not available in the United States), or the AVP II device (used in the United States instead of the AVP III),16,23 carry less risk of embolization. We also noticed that the AVP devices are typically easier to position in the defect and provide a better occlusion rate. This led to a significant evolution of the
Figure 2. Adjusted Kaplan-Meier survival curve for combined outcome (survival free of rehospitalization for CHF, need for surgical reintervention, and death). CHF, congestive heart failure; CI, confidence interval; HR, hazard ratio; PPVR, percutaneous paravalvular leak reduction.
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Table 3. Cox proportional hazards regression for the survival free of rehospitalization for CHF, surgical reintervention, and death for patients with and without a successful PPVR Hazard ratio (95% confidence interval) Candidate predictor Successful PVL reductionz EuroSCORE (per 1% increase) Interval from surgery to PPVR (per year increase) Aortic vs mitral PVL C-index
c2
Principal analysis
Sensitivity analysis I*
Sensitivity analysis IIy
8.36 1.63 0.08
0.34 (0.17-0.71) 1.02 (0.99-1.04) 1.01 (0.98-1.03)
0.43 (0.21-0.88) 1.02 (0.99-1.04) 0.99 (0.97-1.02)
0.41 (0.19-0.86) 1.03 (0.99-1.05) 1.00 (0.98-1.03)
1.06
1.50 (0.70-3.23) 0.83
1.42 (0.66-3.06) 0.84
1.48 (0.69-3.17) 0.83
CHF, congestive heart failure; PPVR, percutaneous paravalvular leak reduction; PVL, paravalvular leak. * In this sensitivity analysis, the procedural success was redefined as a successful prosthesis implantation, with a PVL reduction 1 and a final residual PVL < 3. y In this sensitivity analysis, the need for repeat percutaneous PPVR was added to the principal model’s outcome of rehospitalization for CHF, need for cardiac surgery, and death. z Procedural success in the principal analysis was defined as a PVL reduction of 1 grade without procedural complications.
technique in which more devices can be placed with a greater reduction of the leak. Multivariate analysis showed that a successful PPVRddefined as a successful device implantation and a PVL reduction of at least 1 grade without procedural complicationsdwas associated with an improved survival free of rehospitalization for CHF, surgical reintervention, and death, compared with patients with a failed procedure. Genoni et al. reported in a surgical series that the overall 3-year mortality was higher in a medically treated group than in a surgical group (26% vs 12%) in whom the indication for a surgical reintervention was based on the clinician’s preference. Patients who received surgery were significantly more symptomatic (functional class III and IV) and had lower hemoglobin levels.5 The only other reported series with mid- to long-term follow-up (median follow-up of 11 months, mean follow-up 17 17 months) is the Mayo Clinic experience.23 They showed that long-term clinical efficacy was dependent on residual regurgitation. Indeed, the only patients to report improved symptoms were those with no or mild residual regurgitation. The objective was to reduce PVL as much as possible; a stepwise approach with multiple procedures, or the use of multiple smaller devices to address larger leaks is the strategy we have recently adopted to improve results.26 The long-term mortality rate remains however high, attesting to the very high-risk profile of these patients with PVL who have many comorbidities, including old age, frailty, high prevalence of rheumatic heart disease, multiple previous cardiac surgeries, and deconditioning related to heart failure and/or hemolysis. Limitations The retrospective nature of the study is associated with inherent limitations. Our series is a single-centre experience without systematic serial echocardiographic follow-up and it covers a long period of time over which our understanding and management of leaks was significantly improved. The patients included were very sick with advanced cardiac disease and poor tissue quality because of the number of previous valve surgeries. However, this is a cohort made of consecutive patients in a centre with a dedicated structural intervention program. Because of the limited number of procedures, it was not possible to determine if any particular type of Amplatzer
closure device permits a better outcome. The small number of aortic PVLs precludes comparison between outcome for mitral vs aortic PVL reduction. Similarly, the limited number of bioprosthetic valves (6 patients corresponding to 10.7% of the cohort) precludes comparison between outcome for the different valve types. Finally, there was no systematic brain natriuretic peptide dosage and complete hemolysis blood tests were not routinely performed after discharge. However, significant hemolysis defined as hemolytic anemia requiring > 2 units of blood transfusion within 90 days without any objective bleeding could be assessed during follow-up. Conclusion The procedure is safe with an acceptable complication rate. Successful PPVR is achieved in a reasonable number of patients and is associated with a long-term reduction in the combined end point of rehospitalization for CHF, surgical reintervention, and death. Moreover, failure of a percutaneous attempt does not preclude subsequent surgery as an alternative treatment. Therefore a stepwise approach might represent an attractive strategy for the clinical challenge of PVL. Acknowledgements The authors thank the research nurses, Maude Bergeron and Anna Proietti, for their hard work in the clinical follow-up of this patient cohort. Disclosures Dr R. Ibrahim reports to be a consultant for St Jude Medical. St Jude Medical had no role in the design, subject recruitment or preparation of this report. The other authors have no conflicts of interest to disclose. References 1. Akins CW, Bitondo JM, Hilgenberg AD, Vlahakes GJ, Madsen JC, MacGillivray TE. Early and late results of the surgical correction of cardiac prosthetic paravalvular leaks. J Heart Valve Dis 2005;14:792-9. 2. O’Rourke DJ, Palac RT, Malenka DJ, Marrin CA, Arbuckle BE, Plehn JF. Outcome of mild periprosthetic regurgitation detected by intraoperative transesophageal echocardiography. J Am Coll Cardiol 2001;38:163-6.
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3. Ionescu A, Fraser AG, Butchart EG. Prevalence and clinical significance of incidental paraprosthetic valvar regurgitation: a prospective study using transoesophageal echocardiography. Heart 2003;89:1316-21.
18. Shapira Y, Hirsch R, Kornowski R, et al. Percutaneous closure of perivalvular leaks with Amplatzer occluders: feasibility, safety, and short-term results. J Heart Valve Dis 2007;16:305-13.
4. Rihal CS, Sorajja P, Booker JD, Hagler DJ, Cabalka AK. Principles of percutaneous paravalvular leak closure. JACC Cardiovasc Interv 2012;5: 121-30.
19. Zoghbi WA, Chambers JB, Dumesnil JG, et al. Recommendations for evaluation of prosthetic valves with echocardiography and doppler ultrasound: a report From the American Society of Echocardiography’s Guidelines and Standards Committee and the Task Force on Prosthetic Valves, developed in conjunction with the American College of Cardiology Cardiovascular Imaging Committee, Cardiac Imaging Committee of the American Heart Association, the European Association of Echocardiography, a registered branch of the European Society of Cardiology, the Japanese Society of Echocardiography and the Canadian Society of Echocardiography, endorsed by the American College of Cardiology Foundation, American Heart Association, European Association of Echocardiography, a registered branch of the European Society of Cardiology, the Japanese Society of Echocardiography, and Canadian Society of Echocardiography. J Am Soc Echocardiogr 2009;22:975-1014.
5. Genoni M, Franzen D, Vogt P, et al. Paravalvular leakage after mitral valve replacement: improved long-term survival with aggressive surgery? Eur J Cardiothorac Surg 2000;17:14-9. 6. Leontyev S, Borger MA, Davierwala P, et al. Redo aortic valve surgery: early and late outcomes. Ann Thorac Surg 2011;91:1120-6. 7. Potter DD, Sundt TM, Zehr KJ. Risk of repeat mitral valve replacement for failed mitral valve prostheses. Ann Thorac Surg 2004;78:67-72. 8. Echevarria JR, Bernal JM, Rabasa JM, Morales D, Revilla Y, Revuelta JM. Reoperation for bioprosthetic valve dysfunction. A decade of clinical experience. Eur J Cardiothorac Surg 1991;5:523-6. 9. Hein R, Wunderlich N, Robertson G, Wilson N, Sievert H. Catheter closure of paravalvular leak. EuroIntervention 2006;3:318-25. 10. Sorajja P, Cabalka AK, Hagler DJ, et al. Successful percutaneous repair of perivalvular prosthetic regurgitation. Catheter Cardiovasc Interv 2007;70:815-23. 11. Cortes M, Garcia E, Garcia-Fernandez MA, Gomez JJ, Perez-David E, Fernandez-Aviles F. Usefulness of transesophageal echocardiography in percutaneous transcatheter repairs of paravalvular mitral regurgitation. Am J Cardiol 2008;101:382-6. 12. Lang N, Kozlik-Feldmann R, Dalla Pozza R, et al. Hybrid occlusion of a paravalvular leak with an Amplatzer Septal Occluder after mechanical aortic and mitral valve replacement. J Thorac Cardiovasc Surg 2010;139: 221-2. 13. Nietlispach F, Johnson M, Moss RR, et al. Transcatheter closure of paravalvular defects using a purpose-specific occluder. JACC Cardiovasc Interv 2010;3:759-65. 14. Ruiz CE, Jelnin V, Kronzon I, et al. Clinical outcomes in patients undergoing percutaneous closure of periprosthetic paravalvular leaks. J Am Coll Cardiol 2011;58:2210-7. 15. Swaans MJ, Post MC, van der Ven HA, Heijmen RH, Budts W, ten Berg JM. Transapical treatment of paravalvular leaks in patients with a logistic EuroSCORE of more than 15%: acute and 3-month outcomes of a “proof of concept” study. Catheter Cardiovasc Interv 2012;79:741-7. 16. Sorajja P, Cabalka AK, Hagler DJ, Rihal CS. Percutaneous repair of paravalvular prosthetic regurgitation: acute and 30-day outcomes in 115 patients. Circ Cardiovasc Interv 2011;4:314-21. 17. Pate GE, Al Zubaidi A, Chandavimol M, Thompson CR, Munt BI, Webb JG. Percutaneous closure of prosthetic paravalvular leaks: case series and review. Catheter Cardiovasc Interv 2006;68:528-33.
20. Zoghbi WA, Enriquez-Sarano M, Foster E, et al. Recommendations for evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler echocardiography. J Am Soc Echocardiogr 2003;16:777-802. 21. Mahjoub H, Noble S, Ibrahim R, et al. Description and assessment of a common reference method for fluoroscopic and transesophageal echocardiographic localization and guidance of mitral periprosthetic transcatheter leak reduction. JACC Cardiovasc Interv 2011;4: 107-14. 22. Pencina MJ, D’Agostino RB. Overall C as a measure of discrimination in survival analysis: model specific population value and confidence interval estimation. Stat Med 2004;23:2109-23. 23. Sorajja P, Cabalka AK, Hagler DJ, Rihal CS. Long-term follow-up of percutaneous repair of paravalvular prosthetic regurgitation. J Am Coll Cardiol 2011;58:2218-24. 24. Garcia-Fernandez MA, Cortes M, Garcia-Robles JA, Gomez de Diego JJ, Perez-David E, Garcia E. Utility of real-time three-dimensional transesophageal echocardiography in evaluating the success of percutaneous transcatheter closure of mitral paravalvular leaks. J Am Soc Echocardiogr 2010;23:26-32. 25. Yuan SM, Shinfeld A, Raanani E. Displacement of the Amplatzer occluder device from the mitral paraprosthetic leak. Interact Cardiovasc Thorac Surg 2008;7:1131-3. 26. Jilaihawi H, Ibrahim R. Complex transcatheter paravalvular leak repair. Catheter Cardiovasc Interv 2010;76:194-7.
Supplementary Material To access the supplementary material accompanying this article, visit the online version of the Canadian Journal of Cardiology at www.onlinecjc.ca and at http://dx.doi.org/10. 1016/j.cjca.2013.07.800.
Clinical Research
Percutaneous Paravalvular Leak Reduction: Procedural and Long-term Clinical Outcomes Stephane Noble, MD,a,b E. Marc Jolicoeur, MD, MSc, MHS,a Arsène Basmadjian, MD, MSc,a Sylvie Levesque, MSc,a Anna Nozza, MSc,a Jeannot Potvin, MD,a Jacques Crepeau, MD,a and Reda Ibrahim, MDa a
From the Department of Medicine, Montreal Heart Institute, Universite de Montre al, Montreal, Que bec, Canada b
From the Department of Medical Specialties, Cardiology Division, Universite de Genève, Geneva, Switzerland
ABSTRACT
RESUM E
Background: Significant paravalvular leak (PVL) after prosthetic replacement can result in hemolysis and/or congestive heart failure (CHF). Percutaneous PVL reduction (PPVR) represents an alternative to repeat surgery for a selected population. The purpose of this study was to assess the procedural and long-term clinical efficacy of percutaneous PPVR and its effect on survival free of rehospitalization for CHF, surgical reintervention, and death. Methods: We analyzed a cohort of 56 consecutive patients who underwent 61 PPVRs in our institution between June 2001 and December 2010. Procedural success was defined as a reduction in regurgitation severity free from procedural complications. Patients were followed-up for vital status, clinical events, and symptoms. Results: Patients were aged 65 11 years, with an average logistic EuroSCORE of 19 14%. Indications for PPVR included CHF (61%), hemolysis (9%), or both (30%), caused by mitral (n ¼ 44) or aortic (n ¼ 12) PVL. Procedural success was achieved in 75% of cases. Three major complications, including 2 deaths, occurred during the initial 30-day follow-up in the 42 patients who were treated with a device. After adjusting for the logistic EuroSCORE, prosthesis type (mitral vs aortic), and time interval since the last valve surgery,
Introduction : Une fuite paravalvulaire (FPV) significative après un tique peut entraîner une he molyse de l’insuffisremplacement prothe duction percutane e ance cardiaque congestive (ICC), ou les deux. La re sente une alternative à la reprise chirurgicale de la FPV (RPFPV) repre lectionne s. Le but de cette e tude e tait d’e valuer le pour des patients se clinique à long terme de succès technique de l’intervention et l’efficacite hospitalisation pour ICC, la RPFPV et son effet sur la survie sans re intervention chirurgicale et mortalite . re thodes : Nous avons analyse une cohorte de 56 patients conse cutifs Me tablissement entre juin 2001 et qui ont subi 61 RPFPV dans notre e cembre 2010. Le succès de l’intervention a e te de fini par une dimide de re gurgitation en l’absence de complications lie es à nution du degre dure. Les patients ont eu un suivi de leur statut vital, des la proce ve nements cliniques et de leurs symptômes. e sultats : Les patients e taient âge s de 65 11 ans et avaient un Re EuroSCORE logistique moyen de 19 14 %. Les indications de RPFPV molyse (9 %) ou les deux (30 %), cause es incluaient l’ICC (61 %), l’he par la FPV mitrale (n ¼ 44) ou aortique (n ¼ 12). Le succès de l’in te atteint dans 75 % des cas. Trois (3) complications tervention a e cès, sont apparues durant le suivi initial de majeures, incluant 2 de
Paravalvular leak (PVL) after surgical mitral or aortic valve replacement is the most common cause of nonstructural prosthetic heart valve dysfunction, and it is usually associated with extensive annular calcification, tissue friability, or endocarditis.1 Immediate postoperative PVL is present in 6% to 18% of patients with aortic and in 23% to 32% with mitral valve replacement.2,3 Clinical repercussions of PVL vary from absence of symptoms to congestive heart failure (CHF) and/or significant hemolytic anemia requiring multiple transfusions.4
It is estimated that 3% to 12% of patients undergoing mitral or aortic valve replacement will develop clinically relevant PVL.5 Traditionally, repeat open heart surgery has been the only corrective option for PVL, despite being associated with mortality rates ranging from 4% to 13%.1,6-8 There is also an increased risk of residual or recurrent PVL after repeat surgery because the initial underlying tissue fragility usually persists.1 Percutaneous PVL reduction (PPVR), a less invasive technique, has emerged as an alternative to medical therapy and repeat surgery.9-15 The reported experience with PPVR to date is limited and long-term follow-up is sparse.9,13-18 The present study sought to assess the procedural and long-term clinical efficacy (ie, survival free of rehospitalization for CHF, surgical reintervention, and death) and safety of PPVR in patients with symptomatic PVL anatomically suitable for a percutaneous approach.
Received for publication April 23, 2013. Accepted July 29, 2013. Corresponding author: Dr Reda Ibrahim, Montreal Heart Institute, 5000 Belanger St E, Montreal, Quebec H1T 1C8, Canada. Tel.: þ1-514-376-3330 3800; fax: þ1-514-593-2158. E-mail: [email protected] See page 1427 for disclosure information.
0828-282X/$ - see front matter Ó 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.cjca.2013.07.800
Noble et al. Percutaneous Paravalvular Leak Reduction
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a successful PPVR was associated with a better survival free of rehospitalisation for CHF, need for surgical reintervention, and death compared with patients with a failed PPVR. (hazard ratio ¼ 0.34; 95% confidence interval, 0.17-0.71). Conclusions: PPVR is associated with a reasonable rate of procedural success and favourable cardiovascular outcomes, and represents an appropriate option when technically possible.
te implante . 30 jours chez les 42 patients chez qui un dispositif a e Après l’ajustement de l’EuroSCORE logistique, du type de prothèse (mitrale vs aortique) et de l’intervalle de temps depuis la dernière te associe à une meilchirurgie valvulaire, le succès de la RPFPV a e hospitalisation pour ICC, ne cessite de leure survie sans re intervention chirurgicale et mortalite comparativement aux patients re chec de la RPFPV (rapport de risque ¼ 0,34; intervalle de ayant eu un e confiance à 95 %, 0,17-0,71). e à un taux raisonnable de succès Conclusions : La RPFPV est associe sultats cardiovasculaires favorables, et interventionnel et à des re sente une option approprie e lorsqu’elle est techniquement repre possible.
Methods
prosthesis, diagnosed using Doppler echocardiography. Preprocedural transthoracic and transesophageal echocardiography (TEE) were performed to describe the size, severity, shape, and precise location of the PVL. Prosthetic regurgitation was assessed according to published practice guidelines.19 Severity of regurgitation assessed using echocardiography before publication of theses guidelines used an integrative approach and criteria similar to those later published in the guidelines based on structural 2-dimensional and Doppler data.20 Prosthetic valve function was also evaluated using the American Society of Echocardiography guidelines.19,20 The location of the leak was described according to the clock face approach adapted from the operating room to the catheterization laboratory.21 Procedural complications included death, stroke, tamponade, device embolization, impaired prosthetic function, vascular access site bleeding requiring intervention, and any untoward medical event requiring urgent conversion to open chest surgery occurring within the first 48 hours after the procedure. Procedural success was defined as a device implantation resulting in a PVL reduction of 1 grade, quantified using echocardiographic methods and free of procedural complications assessed using TEE and fluoroscopy. Clinical success was defined as NYHA functional class < III and/or no significant hemolysis, and survival free of reintervention or rehospitalization for CHF. CHF was defined as symptoms corresponding to NYHA functional class grade III. Significant hemolysis was defined as hemolytic anemia requiring > 2 units of blood transfusion within 90 days without any objective bleeding.
Patient population Between June 2001 and December 2010, 56 consecutive patients underwent 61 percutaneous procedures of aortic or mitral PVL reduction in our institution. Patients had to be symptomatic (dyspnea, New York Heart Association [NYHA] 3 despite optimal medical therapy and/or clinically significant hemolytic anemia requiring transfusions) and at high risk for repeat surgery or without surgical options. PPVR was attempted provided that an echocardiographic assessment revealed a PVL anatomically suitable for percutaneous reduction. Patients with active endocarditis or an unstable valve (large dehiscence involving > 40% of the valve circumference or obvious prosthesis rocking) were not considered candidates for the procedure. Data collection and follow-up Baseline demographic characteristics, medical history, cardiac catheterization data, and in-hospital outcomes were collected from medical charts and procedural reports. Risk stratification for surgical reintervention was performed using the logistic EuroSCORE, the Society of Thoracic Surgeons (STS) score, and the Parsonnet score. The logistic EuroSCORE does not take into account the number of previous reinterventions, whereas the STS score and the Parsonnet score do take into account the precise number of repeat surgeries in the risk calculation. Follow-up information and vital status were collected from medical charts, dedicated clinical visits, and by a mailed questionnaire or phone calls when required. Collected information included vital status, need for percutaneous or surgical reintervention related to PVL, NYHA functional class, need for red blood cell transfusion, and rehospitalization for CHF. The national death index was used to determine vital status for nonresponders. Follow-up was 100% complete for the composite outcomes of survival free of rehospitalization for CHF, surgical reintervention, and death at 1 year. All patients were informed of the procedural risks and options, and signed the informed consent for the intervention. The present study was approved by the Institutional Review Board. Clinical definitions PVL corresponds to a regurgitant jet located between the native tissue around the valve and the outer margin of the
PPVR reduction technique Most procedures were performed using general anaesthesia with fluoroscopic and TEE guidance. Antibiotic prophylaxis was administered 30 minutes before the procedure. Unfractioned heparin was administered to maintain an activated clotting time greater than 250 seconds. Briefly, aortic PVLs were performed using a retrograde (retroaortic) approach whereas mitral PVLs were treated using a transseptal antegrade technique. No transapical approach was attempted. Various Amplatzer occluder devices (St Jude Medical, Plymouth, MN) were used during the study period. We initially performed PPVR using exclusively the Amplatzer Duct I (PDA) Occluder device. Between 2005 and 2008, we switched to the Amplatzer Muscular Ventricular Septal Defect (VSD) Occluder device. Since 2008, we have been using either the
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Amplatzer Muscular VSD Occluder device or the Amplatzer Vascular Plug (AVP) III according to the anatomy of the defect. The oval design of the AVP III device makes it the preferred device for the common crescent-shaped leaks whereas the Amplatzer VSD occluder is preferred for circular defects. Before final device release, the absence of interference with the valve prosthesis was evaluated using fluoroscopy and echocardiography. Statistical analysis and modelling of outcomes Continuous variables are described using means SD or medians with interquartile range as appropriate and compared using Wilcoxon rank sum tests. Categorical variables are presented as numbers (percentages), and compared using either c2 or Fisher’s exact tests. Kaplan-Meier methods were used to illustrate the survival free of rehospitalization for CHF, surgical reintervention, and death for patients who did and did not undergo a successful PPVR (primary objective and end point). To adjust for known or expected confounding variables, a multivariable Cox proportional hazards regression was developed. Candidate predictor variables thought to be clinically important were prespecified and included: (1) successful vs failed PPVR; (2) the logistic EuroSCORE; (3) mitral vs aortic PPVR; and (4) time interval between the last valve replacement and the PPVR. The baseline model’s discrimination was evaluated using the c-index.22 No data imputation was performed. Statistical significance was determined at the 2-sided a ¼ 0.05 level. Data analyses were performed using the SAS software package (version 9.2, SAS Institute, Cary, NC). Results
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(Fig. 1). The procedural success rate was 40% (2 of 5 patients) when significant hemolysis was the only indication for PPVR, and it was 78.4% (40 of 51 patients) when the indication involved heart failure with or without hemolysis. Five patients underwent a second percutaneous intervention because of initial failure (n ¼ 1 at 59 days) and persistent or additional symptomatic leaks (n ¼ 4 at 20, 48, 113, and 321 days). For the 61 procedures, the rate of success was 75.4% (46 of 61). Reasons for failed device implantation are listed in Table 2. In 5 patients (9.8%), 2 occluder devices were required to achieve an appropriate PVL reduction. No complications were caused by transseptal puncture. Two patients had transient prosthetic leaflet impingement during attempted implantation precluding the release of any device. Three major periprocedural complications were recorded. In 1 patient, at day 3 the PDA occluder embolized from the mitral position into the aortic bileaflet mechanical prosthesis resulting in rapid death. A second patient developed an early severe hemolytic syndrome, which led to an urgent successful surgical removal of the muscular ventricular septal defect device followed by a surgical repair at day 5 after implantation. A third patient died from renal bleeding 12 days after the implantation without any clear explanation. Mortality rate at 30 days was 8.9% (n ¼ 5) overall, 4.8% (2 of 42) in the group of successful PPVR, and 21.4% (3 of 14) in the group of procedural failure. In the latter group, 1 patient died of a stroke (day 20) and 2 of CHF while in palliative care. At discharge, 81.0% (34 of 42) of the patients with a procedural success were in functional class I and II, whereas 88.1% of them were in functional class > III before the intervention (37 of 42). Hemolysis before and after the procedure is described in Supplemental Table S2 for patients who had a device implanted.
Baseline characteristics From June 2001 to December 2010, 56 consecutive patients underwent 61 PPVRs (Fig. 1). Baseline characteristics are presented in Supplemental Table S1. All patients were symptomatic with heart failure and/or hemolytic anemia requiring repetitive transfusions. Heart failure alone or associated with hemolysis was the most common indication for PPVR (91%). PVL localization was more often mitral (78.6%) than aortic (21.4%). For mitral patients, the most frequent PVL locations were lateral and septal in 21 (47.8%), and 16 patients (36.4%), respectively. On average, patients had undergone 2.4 1.3 thoracotomies (up to 7) with a median time interval between the last surgery and the PPVR of 80.7 (range, 21.9-125.6) months. Significant comorbidities were present in the study population as shown by the elevated logistic EuroSCORE, STS, and Parsonnet scores. Procedural characteristics are listed in Table 1. Initially 1 of the 2 different operators performed procedures using local anaesthesia without TEE guidance (14.8%), corresponding respectively to 38.5% and 10.5% of the aortic and mitral procedures. Procedural in-hospital complications and 30-day outcomes Table 1 also lists the procedural results. Procedural success was achieved in 42 patients in the overall cohort (75.0%)
Mid- to long-term outcomes Patients were followed for an average of 29 27 months and a median of 30 months, providing a total of 156.7 patient-years of information available for the survival analysis. Follow-up information beyond 1 year was available for all patients. Supplemental Table S3 compares the incidence of rehospitalization for CHF, surgical reintervention, and death between patients who did and did not undergo a successful PPVR. The unadjusted survival was statistically nonsignificant (50% vs 57%; hazard ratio, 0.60; 95% confidence interval, 0.27-1.31) between patients with successful and failed PPVR, respectively. During the follow-up period, 21 of 42 (50%) patients with a successful PPVR died and 62% (13 of 21) of these deaths occurred after the first year. Clinical success at 3 months and 1 year were respectively achieved in 69.0% (29 of 42) and 54.8% (23 of 42) of the patients with an initial procedural success. Seven patients (16.7%) required repeat valve surgery despite a successful initial PPVR (at day 5, 32, 148, 229, 435, 757, and 1022). Indications for the surgical reintervention were significant hemolysis in 3 patients (at day 5, 148, and 757) and progression of PVL in 4 patients. The patient who required a surgical reintervention at 32 days had an initial PVL reduction from grade IV to II, but he reported no symptomatic improvement at 30 days and the leak had
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Figure 1. Patient flow chart. PPVR, percutaneous paravalvular leak reduction.
progressed on both sides of the 6-mm VSD device according to echocardiography performed after discharge. The aetiology for this further degradation of the valve attachment was the underlying tissue and suture fragility because of a nondiagnosed culture-negative endocarditis. Out of the 14 patients with initial failed PPVR, 6 patients (43%) required a repeat valve surgery, all of which were performed in the following year. Table 1. Procedural characteristics
Characteristic General anaesthesia TEE guidance Retrograde approach Transseptal approach Transapical approach Procedures with device implanted Device implanted, total n Procedures with 2 devices Occluder devices used PDA occluder mVSD occluder Vascular plug III Two different devices Device not implanted Procedural time, min Fluoroscopic time, min Contrast used (range), mL Residual regurgitation grade 2 Residual regurgitation grade 3 Procedural success with residual regurgitation 2
Aortic and mitral (n ¼ 56) 47 (83.9) 47 (83.9)
42 (75.0) 49 5 (8.9)
Aortic (n ¼ 12)
Mitral (n ¼ 44)
7 (58.3) 7 (58.3) 12 (100) 0 0 7 (58.3) 9 2 (16.7)
40 (90.1) 40 (90.1) 0 44 (100) 0 35 (79.5) 40 3 (6.8)
14 (25.0) 5 (41.7) 22 (39.3) 2 (16.7) 5 (8.9) 0 1 (1.8) 0 14 (25.0) 5 (41.7) 127 46 113 49 50 24 42 24 34 (0-300) 76 (0-300) 22 (39.3) 5 (41.7) 6 (10.7) 1 (8.3) 36 (64.3) 6 (50)
9 (20.4) 20 (45.4) 5 (11.4) 1 (2.3) 9 (20.4) 131 45 53 24 21 (0-255) 17 (38.6) 5 (11.4) 30 (68.2)
Data are presented as mean SD or n (%), unless otherwise indicated. mVSD, muscular ventricular septal defect; PDA, patent ductus arteriosus; TEE, transesophageal echocardiography.
During the follow-up period, 15 patients (35.7%) with successful PPVR were readmitted for symptoms of worsening heart failure (n ¼ 13) and/or significant hemolysis (n ¼ 2). Association between a successful PPVR reduction and long-term outcomes After multivariable adjustment, a successful PPVR was strongly associated with a better survival free of rehospitalization for CHF, surgical reintervention, and death (hazard ratio, 0.34; 95% confidence interval, 0.17-0.71) (Fig. 2). The other candidate predictors (logistic EuroSCORE, left ventricular ejection fraction, and the time interval between the last surgery and the PVL reduction) were not associated with the primary end point (Table 3). We performed sensitivity analyses to assess the robustness of our findings in varying clinical scenarios. Indeed, a successful PPVR remained associated with improved outcomes even when the definition of Table 2. Reasons for failed device implantation Reason Inability to cross with guide wire Inability to cross with catheter Instability of occluder device Inability to size the defecty Prosthetic leaflet impingement
Aortic and mitral (n ¼ 15)* 9 2 1 1 2
(60.0)* (13.3) (6.6) (6.6) (13.3)
Aortic (n ¼ 6)
Mitral (n ¼ 9)
4 (66.6)* 0 0 1 (16.6) 1 (16.6)
5 (55.5) 2 (22.2) 1 (11.1) 0 1 (11.1)
Data are presented as n (%). PVL, paravalvular leak. * Fourteen patients had a failed device implantation including a patient with an aortic PVL having 2 failed procedures caused by the inability to cross the defect with the guide wire. y Before the 3-dimensional era, size and shape of the PVL could be difficult to assess.
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procedural success was modified to include only patients with a final leak of less than Grade 3, or when the study end point was modified to include the need for repeated percutaneous PPVR (Table 3). In all cases the c-indices associated with the models remained greater than 0.80, therefore indicating a good model discrimination. Discussion Until recently, surgical reintervention was the only option to treat PVL. Because of pioneer experience from different centres with encouraging results, PPVR has emerged as an attractive alternative. Our study demonstrates that a successful PPVR compared with a failed procedure is associated with better cardiovascular outcomes, mainly by reducing the number of rehospitalizations for CHF and the need for further reintervention. Considering the relatively high procedural success rate in the hands of a trained interventionalist, PPVR can be considered as a reasonable option in patients at high risk for surgical reintervention. Our cohort of mitral and aortic PPVR represents one of the largest series reported to date permitting the investigation of the feasibility, safety, and short- and long-term clinical outcome of PPVR. To the best of our knowledge, this represents the series with the longest follow-up to date. Procedural success was achieved in 75% and clinical success at 3 months was 69% after a successful device implantation. Our results are concordant with the 3 largest series published to date,14,16,23,24 which show successful implantation rates between 63% and 91% with a concomitant clinical improvement in 51%-89% of patients when a device could be implanted. Despite the very high-risk profiled46%
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of our patients had 3 previous cardiac surgeriesdthe procedural complication rate seems acceptable with only 1 device-related death and 1 early urgent surgical reintervention because of severe hemolysis, induced by the device. Over the years, the procedure has greatly evolved in relation to improvements in imaging, material, and catheterization techniques.24 This has led to an increase in procedural success rates and safety and also a decrease in procedural time. The availability of a steerable transseptal sheath (ie, Agilis catheter, St Jude Medical) has undoubtedly facilitated the mitral PVL approach, particularly when the leak is in a septal location. A major breakthrough was also the availability of hydrophilic and braided delivery sheaths (TorqVue from St Jude Medical, Flexor/Shuttle from Cook, and Destination from Terumo) to cross serpiginous and calcified leaks. Nowadays, 3-dimensional echocardiographyd not available in this seriesdprovides great help to assess the size and shape of the defect and the distance between the defect and the valve prosthesis to select the appropriate device size and type. The inability to size the defect in 1 patient would have probably been solved with the use of 3-dimensional echocardiography. Since the fatal embolization of a PDA device in our series, we are reluctant to use this device, which has only 1 retention disk and a higher risk of embolization.4,25 We believe that 2-disk devices, such as the muscular VSD device, the AVP III device (available in Europe and Canada since 2008 and not available in the United States), or the AVP II device (used in the United States instead of the AVP III),16,23 carry less risk of embolization. We also noticed that the AVP devices are typically easier to position in the defect and provide a better occlusion rate. This led to a significant evolution of the
Figure 2. Adjusted Kaplan-Meier survival curve for combined outcome (survival free of rehospitalization for CHF, need for surgical reintervention, and death). CHF, congestive heart failure; CI, confidence interval; HR, hazard ratio; PPVR, percutaneous paravalvular leak reduction.
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Table 3. Cox proportional hazards regression for the survival free of rehospitalization for CHF, surgical reintervention, and death for patients with and without a successful PPVR Hazard ratio (95% confidence interval) Candidate predictor Successful PVL reductionz EuroSCORE (per 1% increase) Interval from surgery to PPVR (per year increase) Aortic vs mitral PVL C-index
c2
Principal analysis
Sensitivity analysis I*
Sensitivity analysis IIy
8.36 1.63 0.08
0.34 (0.17-0.71) 1.02 (0.99-1.04) 1.01 (0.98-1.03)
0.43 (0.21-0.88) 1.02 (0.99-1.04) 0.99 (0.97-1.02)
0.41 (0.19-0.86) 1.03 (0.99-1.05) 1.00 (0.98-1.03)
1.06
1.50 (0.70-3.23) 0.83
1.42 (0.66-3.06) 0.84
1.48 (0.69-3.17) 0.83
CHF, congestive heart failure; PPVR, percutaneous paravalvular leak reduction; PVL, paravalvular leak. * In this sensitivity analysis, the procedural success was redefined as a successful prosthesis implantation, with a PVL reduction 1 and a final residual PVL < 3. y In this sensitivity analysis, the need for repeat percutaneous PPVR was added to the principal model’s outcome of rehospitalization for CHF, need for cardiac surgery, and death. z Procedural success in the principal analysis was defined as a PVL reduction of 1 grade without procedural complications.
technique in which more devices can be placed with a greater reduction of the leak. Multivariate analysis showed that a successful PPVRddefined as a successful device implantation and a PVL reduction of at least 1 grade without procedural complicationsdwas associated with an improved survival free of rehospitalization for CHF, surgical reintervention, and death, compared with patients with a failed procedure. Genoni et al. reported in a surgical series that the overall 3-year mortality was higher in a medically treated group than in a surgical group (26% vs 12%) in whom the indication for a surgical reintervention was based on the clinician’s preference. Patients who received surgery were significantly more symptomatic (functional class III and IV) and had lower hemoglobin levels.5 The only other reported series with mid- to long-term follow-up (median follow-up of 11 months, mean follow-up 17 17 months) is the Mayo Clinic experience.23 They showed that long-term clinical efficacy was dependent on residual regurgitation. Indeed, the only patients to report improved symptoms were those with no or mild residual regurgitation. The objective was to reduce PVL as much as possible; a stepwise approach with multiple procedures, or the use of multiple smaller devices to address larger leaks is the strategy we have recently adopted to improve results.26 The long-term mortality rate remains however high, attesting to the very high-risk profile of these patients with PVL who have many comorbidities, including old age, frailty, high prevalence of rheumatic heart disease, multiple previous cardiac surgeries, and deconditioning related to heart failure and/or hemolysis. Limitations The retrospective nature of the study is associated with inherent limitations. Our series is a single-centre experience without systematic serial echocardiographic follow-up and it covers a long period of time over which our understanding and management of leaks was significantly improved. The patients included were very sick with advanced cardiac disease and poor tissue quality because of the number of previous valve surgeries. However, this is a cohort made of consecutive patients in a centre with a dedicated structural intervention program. Because of the limited number of procedures, it was not possible to determine if any particular type of Amplatzer
closure device permits a better outcome. The small number of aortic PVLs precludes comparison between outcome for mitral vs aortic PVL reduction. Similarly, the limited number of bioprosthetic valves (6 patients corresponding to 10.7% of the cohort) precludes comparison between outcome for the different valve types. Finally, there was no systematic brain natriuretic peptide dosage and complete hemolysis blood tests were not routinely performed after discharge. However, significant hemolysis defined as hemolytic anemia requiring > 2 units of blood transfusion within 90 days without any objective bleeding could be assessed during follow-up. Conclusion The procedure is safe with an acceptable complication rate. Successful PPVR is achieved in a reasonable number of patients and is associated with a long-term reduction in the combined end point of rehospitalization for CHF, surgical reintervention, and death. Moreover, failure of a percutaneous attempt does not preclude subsequent surgery as an alternative treatment. Therefore a stepwise approach might represent an attractive strategy for the clinical challenge of PVL. Acknowledgements The authors thank the research nurses, Maude Bergeron and Anna Proietti, for their hard work in the clinical follow-up of this patient cohort. Disclosures Dr R. Ibrahim reports to be a consultant for St Jude Medical. St Jude Medical had no role in the design, subject recruitment or preparation of this report. The other authors have no conflicts of interest to disclose. References 1. Akins CW, Bitondo JM, Hilgenberg AD, Vlahakes GJ, Madsen JC, MacGillivray TE. Early and late results of the surgical correction of cardiac prosthetic paravalvular leaks. J Heart Valve Dis 2005;14:792-9. 2. O’Rourke DJ, Palac RT, Malenka DJ, Marrin CA, Arbuckle BE, Plehn JF. Outcome of mild periprosthetic regurgitation detected by intraoperative transesophageal echocardiography. J Am Coll Cardiol 2001;38:163-6.
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Supplementary Material To access the supplementary material accompanying this article, visit the online version of the Canadian Journal of Cardiology at www.onlinecjc.ca and at http://dx.doi.org/10. 1016/j.cjca.2013.07.800.
