Abstract: Objectives. To describe our initial experience with an intracardiac echocardiography (ICE) for guidance of aortic percutaneous paravalvular leak occlusion (PPVLO) and to assess the outcomes after aortic PPVLO. Background. PPVLO has emerged as an alternative to cardiac surgery for patients with symptomatic PVLs. ICE is an appealing alternative to transesophageal echocardiography (TEE) for guidance of percutaneous structural interventions, but experience with ICE for PPVLO guidance is limited. Methods. We performed a retrospective analysis of all aortic PPVLOs performed in our center. The primary endpoints were technical and procedural success. Secondary endpoints included procedure-related complications, mortality, hospital admission due to heart failure, and improvement in New York Heart Association (NYHA) functional class. Results. Ten aortic PPVLOs were included. ICE was used to guide 40% of the aortic PPVLOs. Median follow-up was 22 months (interquartile range, 3-33 months). Mortality was 22% and hospital admission due to heart failure was 33%. Technical and procedural success rates were 90% and 80%, respectively. Median NYHA class improved significantly after the procedure (P<.01). Success was achieved in all ICE cases without any procedure-related complications. Conclusion. In our initial experience with an ICE-guided approach for aortic PPVLO, technical and procedural success were achieved and there were no procedure-related complications.
J INVASIVE CARDIOL 2019;31(11):346-351.
Key words: intracardiac echocardiography, paravalvular leak, percutaneous occlusion
Paravalvular leaks (PVLs) are a common complication after aortic valve replacement. Aortic PVL frequency has been reported to be around 50%, although up to 90% of those are small and have a benign course.1,2 Significant PVL can entail symptoms of heart failure (HF) and hemolysis and have a negative impact in quality of life and prognosis.3
Because patients with symptomatic PVL are high-risk candidates for cardiac surgery, percutaneous PVL occlusion (PPVLO) has emerged as an alternative treatment. Success rates >90% for aortic PPVLO have been reported.4,5 PPVLO has been shown to be comparable to the surgical approach in terms of mortality, need for reintervention, and worsening HF.6,7 Importantly, global experience with PPVLO is still small, and the data available are based mostly in small non-randomized studies, meta-analyses, and multicenter registries.4-7
Although most experience with PPVLO has been obtained under transesophageal (TEE) guidance, intracardiac echocardiography (ICE) may be an option when TEE is not feasible or does not provide good-quality imaging, or when general anesthesia is not desirable.8 However, the experience with ICE in PPVLO is still limited and requires further validation. Importantly, when an ICE-guided strategy is anticipated, a detailed cardiac assessment prior to the procedure with TEE or computed tomography is mandatory to allow a comprehensive anatomic evaluation of the PVL and adequate procedural planning (eg, device sizing).8-10
Our aims were to describe our initial experience with an ICE-guided strategy and to assess the outcomes after aortic PPVLO.
Study population. Between 2012 and 2018, a total of 29 mitral and aortic PPVLOs were performed in our center. Of those, nineteen were targeted mitral PVLs (16 patients) and 10 were targeted aortic PVLs (10 patients). We performed a retrospective cohort analysis of the 10 patients subjected to aortic PPVLO at our center during this time frame.
Referral for PPVLO was based on HF symptoms and/or severe symptomatic hemolytic anemia. An elevated serum lactate dehydrogenase and a decreased serum haptoglobin, in addition to anemia, were required for the diagnosis of intravascular hemolysis. Patients in whom a rocking motion of the prosthesis was observed or who had evidence of active endocarditis were not considered for PPVLO. In patients with symptomatic PVL, the choice between PPVLO, surgery, or optimal medical treatment was based on a case-by-case heart-team discussion. We registered the main baseline clinical characteristics as well as the details of the PPVLO technique. All patients provided a written informed consent before undergoing PPVLO.
Follow-up. Clinical status data were obtained through the analysis of death certificates, clinical notes from admissions to the hospital, and information provided by the patients’ general practitioners when needed. Echocardiographic follow-up was performed routinely the day after the procedure with transthoracic echocardiography (TTE) and 1 month after the procedure with TEE. From there on, patients were assessed with either TTE or TEE, as clinically indicated.
The coprimary endpoints were technical and procedural success. Secondary endpoints included procedure-related complications, mortality, hospital admission due to HF, and improvement in New York Heart Association (NYHA) functional class.
Definitions. PVL was defined as a regurgitant jet, identified by color Doppler, originating from the outside of the sewing ring of a prosthetic valve, documented by TEE. PVL severity was assessed by integrating TTE and TEE data, and graded on a scale from 1 to 3 (where 1 = mild; 2 = moderate; and 3 = severe regurgitation), according to the European Association of Cardiovascular Imaging recommendations.11,12 Technical success was defined as successful delivery of at least 1 closure device without prosthesis dysfunction (or other immediate complications).13 Procedural success was defined as technical success plus improvement of at least 1 grade in the regurgitant jet severity (assessed at the end of the procedure).13 Vascular access-site complications included the presence of a pseudoaneurysm or arteriovenous fistula documented by ultrasound Doppler or the presence of significant vascular-site bleeding with need for blood transfusion and/or hemodynamic compromise. Major complications were defined as any complication resulting in death, acute ischemic events (stroke, myocardial infarction, or peripheral ischemia), device migration, de novo prosthesis dysfunction requiring surgical intervention, or any other complication requiring urgent surgical or percutaneous intervention.
Procedural details. All procedures were executed in a tertiary center by a single operator, with a comprehensive experience in ICE-guided percutaneous intervention for structural heart disease, such as patent foramen ovale, atrial septal defect, and left atrial appendage occlusion. Preprocedural TEE was performed in all cases for adequate characterization of the PVL and exclusion of intracardiac thrombus. All procedures guided by TEE were performed under general anesthesia or deep sedation, and all procedures guided only by ICE were performed under local anesthesia. The closure device was chosen based on the anatomical features, type of valve prosthesis, and echocardiographic dimensions of the PVL. Whenever doubt concerning the device size persisted after thorough echocardiographic evaluation, a peripheral angioplasty balloon was used to assess PVL dimensions. The decision to place a second closure device was made ad hoc by the operator. The closure devices used were the Amplatzer Vascular Plug (AVP) II and III and the Amplatzer Duct Occluder (St. Jude Medical).
The retrograde approach was used systematically. Therefore, two arterial accesses were necessary – one (main) to access the PVL and another to perform an aortography when necessary. The first 6 cases were performed under TEE guidance, and we then switched to an ICE-guided strategy for the last 4 cases. Whenever ICE was used, a femoral venous access was necessary to place the ICE probe in the right atrium; Acuson AcuNav (Siemens Medical Solutions) or ViewFlex Xtra (St. Jude Medical) ICE catheters were used. Through the main arterial access, a guidewire was passed through the PVL and the device delivery system was advanced into the left ventricle. Systematic evaluation with ultrasound and fluoroscopy was performed to optimize device positioning and to ensure normal functioning of the prosthetic valve. Figure 1 and Videos 1-4 show an example of a percutaneous occlusion of an aortic PVL under ICE guidance.
Statistical analysis. The normality of distribution of continuous variables was tested using the Kolmogorov-Smirnov test. Continuous variables (without a normal distribution) are expressed as median and interquartile range (IQR) and categorical variables are expressed as frequencies and percentages. Categorical variables were compared using the Chi-squared test. The Wilcoxon test was used to assess the variation of medians for continuous variables before and after the procedure. Statistical significance was accepted for P-values <.05. SPSS Statistics, version 20 (IBM) was used to perform the statistical analyses.
Baseline characteristics. A total of 10 aortic PPVLOs were performed on 10 patients from April 2012 to April 2018. Baseline patient characteristics are summarized in Table 1. The majority of patients (60%) were female, and the median age was 70 years (IQR, 51-77 years). In all cases, symptomatic HF was the main reason for referral to PPVLO. Anemia was present in 8 patients (80%), four of whom had documented hemolysis. Median hemoglobin was 11 g/dL (IQR, 10.00-12.25 g/dL). Median NYHA class at baseline was 3 (IQR, 2.75-4.00) and 8 patients (80%) were in NYHA class ≥3. All patients were under anticoagulation with warfarin. Left ventricular ejection fraction was <50% in 3 patients (30%) and other significant valvular disease (moderate or severe) was present in 4 patients (40%); the most frequent concomitant valvular disease was moderate or severe tricuspid regurgitation, which was present in 30% of the entire cohort.
Procedural details and early outcomes. Procedural details are displayed in Table 2. PPVLO was undertaken more often in mechanical prostheses (90%). PVLs were severe in 8 cases (80%) and moderate in 2 cases (20%). The procedure was guided by TEE in 6 cases (60%) and by ICE in 4 cases (40%).
Technical and procedural success were achieved in 9 patients (90%) and 8 patients (80%), respectively. Median leak severity improved from grade 3 (IQR, 2.75-3) to grade 1.5 (IQR, 1.00-2.25) (P=.01). After the procedure, leak severity was none in 1 patients (10%), mild in 4 patients (40%), moderate in 3 patients (30%), and severe in 2 patients (20%).
The AVP II and AVP III were each implanted in 4 of the successful cases (40% each), and the Duct Occluder was implanted in 2 successful cases (20%). In 2 cases (20%), two devices were implanted (2 AVP II devices in 1 case and 2 AVP III devices in the other case). Technical failure occurred in 1 procedure (10%) and was due to immediate device embolization. This was the only severe intraprocedural complication. In this case, an AVP II placed in an aortic PVL under TEE guidance migrated into the left ventricle, and percutaneous retrieval of the device was not possible. The patient died due to refractory HF and septic shock during the index admission; this was the only in-hospital death registered in our cohort. Also, no vascular access-site complications were observed. Further information regarding procedure-related complications is provided in Table 3.
Follow-up and outcomes. As mentioned above, 1 patient died during the index admission, leaving 9 patients for follow-up over a median period of 22 months (IQR, 3-33 months). All-cause mortality during follow-up occurred in 2 cases (22%), including cardiovascular mortality in 1 patient (11%). Mortality rate at 1 year remained at 22%. Hospital readmission due to HF occurred in 3 cases (33%); the first readmission occurred during the first year of follow-up in all cases. Endocarditis after PPVLO occurred in 1 case (11%). It was diagnosed 3 months after the procedure and resulted in the patient’s death. Median NYHA class improved from 3 (IQR, 2.75-4.00) to 2 (IQR, 1.25-2.00) (P<.01) after PPVLO. After the procedure, 78% of the patients were in NYHA class ≤2. Figure 2 shows the variation in NYHA class before and after the procedure.
ICE-guided PPVLO. Of the 10 PPVLOs in our series, four (40%) were guided by ICE and 6 (60%) were guided by TEE. Technical and procedural success were achieved in all procedures guided by ICE. There were no major procedure-related complications in the ICE group. There were no statistical differences between ICE and TEE for these endpoints (technical success, 100% vs 83%, respectively [P>.99]; procedural success, 100% vs 67%, respectively [P=.47]; and major procedure-related complications, 0% vs 17% [P>.99]). Table 4 illustrates the main clinical and procedural characteristics of the cases guided by ICE and TEE.
The main findings of our study were: (1) in our initial experience with ICE for guidance of aortic PPVLOs, there were no major complications and procedural success was achieved in all cases; and (2) in our small cohort, aortic PPVLO was associated with an improvement in HF symptoms.
Rationale for PPVLO. Worldwide, PPVLO success rates of 70%-91% have been reported, although the definition of success varies significantly across studies.4-7,14-16 Our results showed technical and procedural success rates of 90% and 80% in 10 patients, respectively, consistent with previous reports of aortic PPVLO.4,5
PPVLO has previously been shown to be safe, with major complications ranging between 6%-9%,4,14,15 and to be associated with fewer short-term adverse events than the surgical approach.7
Our data showed that both mortality (2 of the 9 successful PPVLOs; 22%) and hospital admission due to HF (3 of the 9 technically successful PPVLOs; 33%) were frequent during follow-up. Importantly, we found a significant improvement in NYHA class, reflecting a positive impact in quality of life. In a recent meta-analysis comparing PPVLO (both aortic and mitral) with a surgical approach, pooled 1-year mortality and readmission due to HF after PPVLO were 17% and 26%, respectively.6 Of note, previous studies comparing PPVLO with surgery suggested that although success rates are higher with a surgical approach, long-term survival is similar with both techniques.6,7
Impact of center volume. In a large series from Garcia et al,4 operator experience was an independent predictor of procedural success for mitral PVLs, with procedural success rates of 65% for centers with a smaller number of cases. Sorajja et al17 showed that with more experienced operators, procedural and fluoroscopy times, contrast volume, length of hospital stay, and major adverse cardiovascular events were lower. In our study, both technical and procedural success were numerically higher in the ICE group. However, an ICE-guided strategy was only adopted in the last cases performed at our center. Thus, this trend toward a better result with ICE is probably the reflexion of the learning curve.
Taking these findings into consideration, it is reasonable to believe that with growing operator experience and with technological evolution and development of new devices with a more favorable design for the occlusion of PVLs, the results of PPVLO are expected to improve in the near future.
Rationale for an ICE-guided approach and initial experience. ICE is now being used more often to guide complex structural interventions, such as percutaneous left atrial appendix occlusion, with comparable results to TEE.18,19 However, experience with ICE for PPVLO guidance is still small, and its feasibility and safety have been suggested only in small series and case reports.8-10 The most appealing advantage of an ICE-guided approach for PPVLO is that it precludes the need for general anesthesia or deep sedation, which is particularly important in such a fragile population. From a practical standpoint, ICE may also reduce the number of personnel needed for PPVLO, as it obviates the need for an anesthesiology team and a dedicated TEE operator. Another theoretical advantage of ICE is that it may provide better visualization of the anterior portion of mechanical aortic prostheses, which is often obscured by shadow artefacts when assessed by TEE.
Our group used ICE for single aortic PVLs, with the probe sited in the right atrium. In these selected cases, technical and procedural success was achieved in all cases, and there were no procedure-related complications, including VASC. In a previous study by Ruparelia and colleagues,8 ICE was used to guide both aortic and mitral PPVLOs in 18 patients with a technical success (defined as leak reduction to <moderate) of 72%. This group reported 1 case of device embolization to the left ventricle and no other major complications, and no vascular access-site complications requiring intervention.
Importantly, although ICE may be useful to guide PPVLO, careful anatomic assessment of the PVL with other imaging modalities such as TTE and TEE and/or computed tomography is mandatory before the procedure.
Study limitations. This is a retrospective analysis of a small series of patients. The primary purpose of this study was to demonstrate that ICE can be used for guiding selected cases of aortic PPVLO and not to advocate for the routine use of this technique. In our point of view, evidence for a widespread use of ICE for guiding PPVLO is still weak, and the very small number of patients included mandates caution while interpreting and extrapolating our results. Furthermore, at our center, there is a wide experience with ICE for guidance of other structural interventions such as occlusion of patent foramen ovale, atrial septal defects, and left atrial appendage, which probably influenced our results positively. The observational, retrospective design of this study confers an inevitable bias and thus limits data extrapolation. In addition, this study lacks a control group that allows comparison of PPVLO with surgical and/or medical therapy.
All things considered, our results should be interpreted with caution and in the light of previous studies, and our conclusions should be regarded as hypotheses that need further validation.
In our initial experience with an ICE-guided approach for aortic PPVLO, technical and procedural success were achieved in all cases and there were no procedure-related complications. In this study, aortic PPVLO was associated with an improvement in NYHA functional class.
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From the 1Serviço de Cardiologia, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; and 2Faculdade de Medicina da Universidade de Coimbra, Coimbra, Portugal.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.
Manuscript submitted February 9, 2019, provisional acceptance given May 29, 2019, final version accepted June 4, 2019.
Address for correspondence: Joana Maria Ribeiro, MD, MSc, Serviço de Cardiologia, Centro Hospitalar e Universitário de Coimbra – Pólo Hospital Geral, Quinta dos Vales, 3041-801, Coimbra, Portugal. Email: firstname.lastname@example.org