Abstract: Objectives. In recent years, transcatheter treatment techniques for tricuspid regurgitation (TR) have rapidly evolved. Cardiac remodeling analysis beyond clinical outcome assessment following transcatheter tricuspid repair is still lacking. The aim of the present case series was to analyze cardiac remodeling after tricuspid valve repair using the edge-to-edge MitraClip technique. Methods. Echocardiographic analysis was performed prior to MitraClip implantation and at 3-month and 6-month follow-up exams. Results. Six consecutive patients undergoing MitraClip implantation between April 2017 and March 2018 at our institution were enrolled. During follow-up, TR reduction was durable in all patients, without recurrence of severe TR. Compared to baseline, right ventricular function improved in 5 out of 6 patients. Reduction in right ventricular area was observed in the majority of patients and reduction in right atrial volume was observed in all subjects. Patients also experienced beneficial left cardiac remodeling. Conclusion. The present series indicates that transcatheter treatment of severe TR using the edge-to-edge MitraClip technique can lead to reverse cardiac remodeling, which is not commonly seen in surgically treated patients.
J INVASIVE CARDIOL 2019;31(4):89-93.
Key words: MitraClip, reverse remodeling, transcatheter tricuspid repair, tricuspid regurgitation
Tricuspid regurgitation (TR) most often occurs secondary to right ventricular (RV) dilation. The leading mechanism in this setting is tricuspid annulus dilation and papillary muscle displacement. Frequently, RV dilation emerges as a result of left heart disease with backward transmission of pressure and volume overload from the left heart to the RV.
Since moderate-to-severe TR is associated with increased mortality and morbidity,1-3 surgical repair of severe TR is offered as a therapeutic option that can improve long-term survival.4 However, tricuspid surgery is associated with increased operative mortality ranging from 10%-17%5-7 and can exceed 20% in elderly patients with comorbidities.8 Given the high prevalence and clinical relevance of severe TR, transcatheter strategies have been introduced with initial promising results.9-11 The use of the MitraClip device (Abbott) for TR repair is one such percutaneous technique, and has shown beneficial clinical results up to 12 months of follow-up. The aim of the present study was to assess the cardiac remodeling process following MitraClip implantation in a series of patients with severe TR.
Population. All consecutive patients with severe secondary TR undergoing transcatheter tricuspid valve repair with the MitraClip device at our institution were enrolled into the present prospective, open-label, observational study (NCT03488732). The only exclusion criterion was the absence of a written informed consent. The study was approved by the local ethics committee and was performed according to the Declaration of Helsinki.
Echocardiography assessment. Patients underwent transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) assessments for evaluation of the severity and etiology of TR, ventricular function, and dimensions for confirmation of suitability for the MitraClip procedure. Special transgastric views were performed to analyze jet origin and coaptation defects. In cases of insufficient visualization of the tricuspid valve in the transgastric view, patients were unsuitable for tricuspid clipping due to inadequate clip navigation during implantation.
TR severity was graded on a staged scale (mild, moderate, or severe) according to current guidelines.12 Left ventricular (LV) function was assessed using biplane measurements in two-chamber and four-chamber views. RV function was expressed by means of fractional area change calculated from apical four-chamber view. Right atrial (RA) and left atrial (LA) volumes were calculated by area-length method. In cases of atrial fibrillation, five measurements were taken and the mean value was built afterward.
All TTE and TEE exams were performed according to the guidelines of the American Society of Echocardiography13,14 by experienced cardiologists who were not involved in the procedure (JL and PB).
Procedure and follow-up. Preprocedural operative risk was calculated using the logistic EuroScore I.15 Patients were considered for tricuspid clipping in cases of high operative risk, defined as EuroScore I >20% and/or age ≥85 years. Patients with severe pulmonary hypertension (systolic pulmonary artery pressure estimated by echocardiography >60 mm Hg) were not treated. All procedures were performed under general anesthesia and via transfemoral access. Fluoroscopy and TEE were used for guidance during the implantation. Procedural details have been described in detail previously.16 At the end of the implantation, TTE and TEE were used to assess acute procedural success, which was defined as implantation of at least one clip, residual TR ≤ class II, and absence from conversion to open-heart surgery. Complications were assessed using VARC-2 definitions.17
Follow-up was performed routinely at 3 months and 6 months; exams comprised clinical examination and echocardiographic assessments of TR severity, changes in right and left cardiac dimensions, left and right systolic function, and RV-RA gradient.
Statistical analysis. Categorical variables were expressed as numbers and percentages. Since the present work included only 6 patients, no detailed statistical analysis was performed to assess changes in cardiac dimension and function between baseline and follow-up. Instead, remodeling assessment was done on a descriptive basis.
Baseline and procedural characteristics. Between April 2017 and March 2018, a total of 6 patients were enrolled in the present study. Median patient age was 84 years (interquartile range [IQR], 79-90 years) and median logistic EuroScore was 25% (IQR, 22%-29%). The remaining baseline clinical details are displayed in Table 1. TR was severe and had functional etiology in all patients. No patient had concomitant valvular dysfunction of more than mild severity at baseline or at follow-up.
Procedural success was achieved in all patients without hospital death or any other hospital complications. Procedural details are outlined in Table 2.
Cardiac remodeling. During follow-up, TR reduction was durable in all patients without recurrence of severe TR within the first 6 months (Figure 1A). Clinical improvement at 6-month follow-up compared to baseline was achieved in all patients (Figure 1B). RV function assessed by FAC increased in 5 out of 6 patients (Figure 2A). Also, reductions in both end-diastolic and end-systolic RV area (Figures 2B and 2C) were observed in the majority of patients. A decline in RA volume could be noticed in all subjects (Figure 2D). Patient #3, who showed worsening RV function during follow-up, similarly did not respond adequately in terms of RV dimensions and RA volume. Echocardiographically estimated RV-RA gradient showed only very small changes during follow-up.
LV function improved in 2 patients, was preserved in 2 patients, and declined in 1 patient (Figure 3A). Changes in LV volume were small in all but 1 patient (Figures 3B and 3C); this patient was the only one with an increase in LA volume. All other subjects experienced a decline in LA volume (Figure 3D).
Transcatheter tricuspid valve repair has gained a lot of attention in interventional cardiology in recent years. Currently, off-label use of the MitraClip is the most often performed technique. The feasibility of this approach has been proved and clinical results are available for up to 12 months following implantation.16,18,19 However, the potential impact of tricuspid clipping on cardiac remodeling beyond 30 days of follow-up has not been studied yet.
In the present patient series, reduction in right heart dimensions and improved RV function were observed in almost all patients. With regard to surgical tricuspid repair, few data assessing cardiac remodeling are available. Two reports show surgical repair to be associated with reduction in RV dimensions20 and improvement in RV function.21 However, the restoration in RV function was observed over a period of several years after an initial drop in RV function directly after surgery in approximately 50% of that population.21 Early deterioration in RV function was also reported in other analyses assessing tricuspid surgery.22 Since worsening RV function was also observed in surgical aortic valve replacement in contrast to transcatheter aortic valve replacement23 and our series of transcatheter tricuspid valve repair, this mechanism may be specifically attributable to valvular surgery. Myocardial injury caused by cardioplegia and/or postcardiotomy syndrome is a possible explanation for this hypothesis. Another cause for the lack of remodeling not associated with surgery may be the increased RV afterload due to the absence of TR acting as an overflow outlet. This might explain the absent reverse remodeling of patient #3 in our series.
In contrast to tricuspid surgery, MitraClip implantation appears to offer reverse remodeling even in patients with RV dysfunction. Since impaired RV performance is associated with poor outcomes in surgically treated patients,24 the guidelines do not recommend TR surgery under these conditions.12 However, 3 patients with RV dysfunction in our series underwent TR repair and showed reverse cardiac remodeling. This may again be explained by less myocardial injury with the transcatheter approach. Another possibility is the higher grade of residual TR seen in transcatheter repair16,19 when compared to TR surgery.22 Beside the larger afterload associated with higher reductions of TR, a reduced preload consisting only of blood flow from the vena cava without the additional regurgitant volume after tricuspid repair can be associated with further deterioration of an already impaired RV.
In our series, slight reverse remodeling of the left heart was also detected. This is most likely caused by the increased right cardiac output and, consequently, improved preload of the LV. Reverse right and left cardiac remodeling underlines the beneficial effect of tricuspid clipping on the pathophysiological process associated with severe TR, and ultimately may stop further progression of heart failure in these patients.
Study limitations. Several limitations need to be noted. First, the present analysis is a case series comprised of only 6 patients. Therefore, a systematic statistical analysis could not be performed. Second, RV function was expressed as a mean of the fractional area change. Other measurements, such as tissue Doppler-derived RV systolic excursion velocity, speckle tracking, and three-dimensional echocardiography, were not performed for remodeling assessment. Third, the present data are observational and therefore no comparisons with surgically or medically treated patients are possible.
The present series indicates that transcatheter treatment of severe tricuspid regurgitation using the edge-to-edge MitraClip technique can lead to reverse cardiac remodeling, which is not commonly seen in surgically treated patients. This observation needs further evaluation in larger-scale trials.
- Nath J, Foster E, Heidenreich PA. Impact of tricuspid regurgitation on long-term survival. J Am Coll Cardiol. 2004;43:405-409.
- Sadeghpour A, Hassanzadeh M, Kyavar M, et al. Impact of severe tricuspid regurgitation on long term survival. Res Cardiovasc Med. 2013;2:121-126.
- Topilsky Y, Nkomo VT, Vatury O, et al. Clinical outcome of isolated tricuspid regurgitation. JACC Cardiovasc Imaging. 2014;7:1185-1194.
- Van de Veire NR, Braun J, Delgado V, et al. Tricuspid annuloplasty prevents right ventricular dilatation and progression of tricuspid regurgitation in patients with tricuspid annular dilatation undergoing mitral valve repair. J Thorac Cardiovasc Surg. 2011;141:1431-1439.
- Kaplan M, Kut MS, Demirtas MM, et al. Prosthetic replacement of tricuspid valve: bioprosthetic or mechanical. Ann Thorac Surg. 2002;73:467-473.
- Kilic A, Saha-Chaudhuri P, Rankin JS, et al. Trends and outcomes of tricuspid valve surgery in North America: an analysis of more than 50,000 patients from the Society of Thoracic Surgeons database. Ann Thorac Surg. 2013;96:1546-1552; discussion p. 1552.
- Ratnatunga CP, Edwards MB, Dore CJ, et al. Tricuspid valve replacement: UK Heart Valve Registry mid-term results comparing mechanical and biological prostheses. Ann Thorac Surg. 1998;66:1940-1947.
- LaPar DJ, Likosky DS, Zhang M, et al. Development of a risk prediction model and clinical risk score for Isolated tricuspid valve surgery. Ann Thorac Surg. 2018;106:129-136.
- Figulla HR, Kiss K, Lauten A. Transcatheter interventions for tricuspid regurgitation – heterotopic technology: TricValve. EuroIntervention. 2016;12:Y116-Y118.
- Latib A, Agricola E, Pozzoli A, et al. First-in-man implantation of a tricuspid annular remodeling device for functional tricuspid regurgitation. JACC Cardiovasc Interv. 2015;8:e211-e214.
- Schofer J, Bijuklic K, Tiburtius C, et al. First-in-human transcatheter tricuspid valve repair in a patient with severely regurgitant tricuspid valve. J Am Coll Cardiol. 2015;65:1190-1195.
- Baumgartner H, Falk V, Bax JJ, et al. 2017 ESC/EACTS guidelines for the management of valvular heart disease. Eur Heart J. 2017;38:2739-2791.
- Lang RM, Badano LP, Mor-Avi V, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015;28:1.e14-39.e14.
- Rudski LG, Lai WW, Afilalo J, et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr. 2010;23:685-713.
- Roques F, Nashef SA, Michel P, et al. Risk factors for early mortality after valve surgery in Europe in the 1990s: lessons from the EuroSCORE pilot program. J Heart Valve Dis. 2001;10:572-577.
- Nickenig G, Kowalski M, Hausleiter J, et al. Transcatheter treatment of severe tricuspid regurgitation with the edge-to-edge MitraClip technique. Circulation. 2017;135:1802-1814.
- Kappetein AP, Head SJ, Genereux P, et al. Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document (VARC-2). Eur J Cardiothorac Surg. 2012;42:S45-S60.
- Besler C, Orban M, Rommel KP, et al. Predictors of procedural and clinical outcomes in patients with symptomatic tricuspid regurgitation undergoing transcatheter edge-to-edge repair. JACC Cardiovasc Interv. 2018;11:1119-1128.
- Orban M, Besler C, Braun D, et al. Six-month outcome after transcatheter edge-to-edge repair of severe tricuspid regurgitation in patients with heart failure. Eur J Heart Fail. 2018;20:1055-1062.
- Kim JB, Jung SH, Choo SJ, et al. Clinical and echocardiographic outcomes after surgery for severe isolated tricuspid regurgitation. J Thorac Cardiovasc Surg. 2013;146:278-284.
- Chikwe J, Itagaki S, Anyanwu A, et al. Impact of concomitant tricuspid annuloplasty on tricuspid regurgitation, right ventricular function, and pulmonary artery hypertension after repair of mitral valve prolapse. J Am Coll Cardiol. 2015;65:1931-1938.
- Bertrand PB, Koppers G, Verbrugge FH, et al. Tricuspid annuloplasty concomitant with mitral valve surgery: effects on right ventricular remodeling. J Thorac Cardiovasc Surg. 2014;147:1256-1264.
- Cremer PC, Zhang Y, Alu M, et al. The incidence and prognostic implications of worsening right ventricular function after surgical or transcatheter aortic valve replacement: insights from PARTNER IIA. Eur Heart J. 2018;39:2659-2667.
- Kim YJ, Kwon DA, Kim HK, et al. Determinants of surgical outcome in patients with isolated tricuspid regurgitation. Circulation. 2009;120:1672-1678.
From the 1I. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany; and 2DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
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 November 1, 2018, and accepted November 12, 2018.
Address for correspondence: Jakob Ledwoch, MD, I. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany. Email: email@example.com