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Correlation of tricuspid regurgitation and new pacemaker implantation in patients undergoing transcatheter aortic valve implantation
IJCA-26159; No of Pages 5 International Journal of Cardiology xxx (2017) xxx–xxx
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International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Correlation of tricuspid regurgitation and new pacemaker implantation in patients undergoing transcatheter aortic valve implantation Dimitry Schewel a,⁎, Jury Schewel a, Michael Schlüter b, Felix Kreidel a, Tobias Schmidt a, Michael Schmoeckel c, Albrecht Elsässer d, Karl-Heinz Kuck a, Christian Frerker a a
Asklepios Klinik St. Georg, Department of Cardiology, Hamburg, Germany Asklepios proresearch, Hamburg, Germany Asklepios Klinik St. Georg, Department of Cardiac surgery, Hamburg, Germany d Klinikum Oldenburg AöR, Department of Cardiology, Oldenburg, Germany b c
a r t i c l e
i n f o
Article history: Received 10 October 2017 Received in revised form 6 February 2018 Accepted 6 March 2018 Available online xxxx Keywords: TAVI Conduction abnormality Tricuspid regurgitation Aortic valve stenosis Ventricular overload Pacemaker
a b s t r a c t Aims: Conduction abnormalities (CA), in particular complete atrioventricular block (CAVB), requiring permanent pacemaker (PPM) implantation, are frequent complications after transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis (AS). However, the potential mechanisms are still incompletely understood. The objective of this retrospective study was to determine further predictors of CAVB after TAVI in patients without the known predictors. Methods and results: This study included patients without prior CA/PPM who underwent TAVI of a balloonexpandable valve (Sapien or Sapien XT or Sapien 3). Of 563 patients (81.2 ± 6.9 years, 245 men [43.5%], logistic EuroSCORE 22.2 ± 14.1%, STS PROM 5.9 [3.4–8.0]) who were treated by TAVI at our institution between July 2008 and January 2016, 61 (10.8%) developed a permanent CAVB after the procedure. In a multivariable logistic regression analysis moderate/severe tricuspid regurgitation (TR) (OR 2.05; 95% CI 1.18–3.55; p = 0.010) was identified as an independent predictor for new CAVB after TAVI. Moreover, patients with more pronounced TR presented with increased left and right ventricular overload (left ventricular (LV) end-diastolic diameter, LV end-diastolic pressure), pulmonary pressures, NT-proBNP, and prevalence of mitral regurgitation ≥II, whereas LV ejection fraction, TAPSE and cardiac output were decreased. Conclusions: PPM implantation is a frequent complication in patients undergoing TAVI. Increasing severity of TR seems to be a consequence of left and right ventricular overload caused by severe AS and is a significant predictor of new CAVB after TAVI. Condensed abstract: Conduction abnormalities (CA) requiring permanent pacemaker (PPM) implantation, are frequent complications after transcatheter aortic valve implantation (TAVI). This study included patients without prior CA/PPM who underwent TAVI. Of 563 patients 61 (10.8%) developed a permanent CAVB after the procedure. In a multivariable logistic regression analysis moderate/severe tricuspid regurgitation (TR) (OR 2.05; 95% CI 1.18–3.55; p = 0.010) was identified as an independent predictor for new CAVB. Therefore, in patients with moderate/severe TR utmost care should be taken to avoid procedural factors conducive to mechanical irritation of the conduction system, resulting in pacemaker dependency. © 2017 Elsevier B.V. All rights reserved.
1. Introduction Transcatheter aortic valve implantation (TAVI) is preferable recommended in high- and intermediate surgical risk patients with symptomatic severe aortic stenosis (AS) [1–6]. Injury of the conduction system is a known complication of TAVI procedures. As the atrioventricular (AV) conduction system is anatomically close to the aortic valve complex, any ⁎ Corresponding author at: Department of Cardiology, Asklepios Klinik St. Georg, Lohmühlenstr. 5, 20099 Hamburg, Germany. E-mail address: [email protected] (D. Schewel).
mechanical irritation could result in conduction abnormalities, particularly left bundle branch block (LBBB) or complete atrioventricular block (CAVB) requiring a permanent pacemaker (PPM) implantation [7–12]. The incidence of PPM implantations after TAVI has been reported to be 0–12% in balloon-expandable prostheses (e.g. Edwards Sapien) [11–13] and 18–49% in self-expanding prostheses (e.g. Medtronic CoreValve) [13]. Previous studies have shown that PPM implantation does not have an effect on survival after TAVI [14,15]. Nevertheless, it is associated with increased length of hospital stay and higher costs [8,16]. Furthermore, new PPM implantation could result in reduced left ventricular function recovery [7,17] due to impaired AV synchrony
https://doi.org/10.1016/j.ijcard.2018.03.030 0167-5273/© 2017 Elsevier B.V. All rights reserved.
Please cite this article as: D. Schewel, et al., Correlation of tricuspid regurgitation and new pacemaker implantation in patients undergoing transcatheter aortic valve implantati..., Int J Cardiol (2017), https://doi.org/10.1016/j.ijcard.2018.03.030
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D. Schewel et al. / International Journal of Cardiology xxx (2017) xxx–xxx
by right ventricular pacing [18]. Previous studies have described different predictors for new PPM such as implantation depth [11,19], prosthesis oversizing [11], access route [12], device selection [12], and preexisting right bundle branch block (RBBB) [12]. The aim of this retrospective study was to analyze patients without the known predictors and to find additional independent prognostic factors for new PPM after TAVI of a balloon expandable valve. 2. Methods 2.1. Patient population and study design A total of 1328 patients with severe AS underwent TAVI at our hospital between July 2008 and January 2016. Patients with pre-existed PPM (n = 155) or RBBB (n = 65), patients who underwent emergency TAVI (n = 44), and those with degenerated biological aortic prosthesis (n = 59) were excluded from this analysis. Additionally, only patients who received an Edwards Sapien (n = 25, 4.4%), Sapien XT (n = 251, 44.6%) or Sapien 3 (n = 287, 51%) prosthesis were included. Thereby, 563 patients treated with a balloonexpandable valve were included in the final retrospective analysis. These patients were divided into two groups according to the need for a new PPM after TAVI (no PPM vs. new PPM: 502 (89.2%) vs. 61 (10.8%); Fig. 1A). 2.2. TAVI procedure Indication for aortic valve replacement was the presence of severe, symptomatic AS with an aortic valve area ≤ 1.0 cm2 (≤0.6 cm2/m2) as determined by echocardiography. The patients' operative risk was assessed by calculation of the logistic EuroSCORE and the Society of Thoracic Surgeons predicted risk of mortality (STS PROM). A “Heart Team” consisting of an interventional cardiologist, a cardiac surgeon, and an anesthesiologist evaluated candidates and did the final decision for TAVI procedures. Pre-procedural screening was done by transthoracic and transesophageal echocardiography (annulus diameter, annular morphology, amount of valvular calcification), left heart catheterization, aortic root angiography, and peripheral vascular angiography for evaluation of the aortic annulus (diameter) and the access route. Written informed consent was obtained from all patients. TAVI procedures have been described previously [20,21]. Outcome parameters were assessed according to the Valve Academic Research Consortium (VARC)-2 criteria [22]. Follow-up was scheduled at 30 days and 12 months after discharge. 2.3. Data collection and definitions The patients' functional capacity, as defined by the New York Heart Association (NYHA), was documented before TAVI and at each follow-up visit. Laboratory parameters (N-terminal pro-brain natriuretic peptide [NT-proBNP], creatinine, glomerular filtration rate [GFR], and blood urea nitrogen [BUN]) were collected at baseline. NT-proBNP was measured by a chemoluminescence immunoassay (e411, Roche Diagnostics GmbH, Grenzach-Wyhlen, Germany). The estimated GFR was calculated via the CKD-EPI formula [23]. All patients underwent an extended transthoracic echocardiographic examination by different operators including assessment of aortic valve with mean transvalvular pressure gradient (Pmean), aortic peak velocity (Aortic Vmax) and aortic valve area (AVA) via the continuity equation, severity of regurgitation (AR), left ventricular ejection fraction (LVEF), and severity of mitral regurgitation (MR) and tricuspid regurgitation (TR). Grading of MR and TR was based on an integrated approach of the current European guidelines
[24–26] and graded as 0 (none), I (mild), II (moderate), and III (severe). Furthermore, left atrial diameter (LA), left ventricular end-systolic (LVESD) and end-diastolic diameters (LVEDD), thickness of the interventricular septum (IVS) and left ventricular posterior wall (PW), as well as the ratio of mitral peak velocity of early filling (E) to early diastolic mitral annular velocity (E') as a parameter of diastolic function (E/E' ratio), and tricuspid annular plane systolic excursion (TAPSE) were documented. A 7Fr Swan-Ganz catheter (Edwards Lifesciences, Irvine, CA, USA) was routinely used for hemodynamic measurements during the procedure before and after deployment of the prosthesis. Right atrial pressure (RAP), pulmonary capillary wedge pressure (PCWP), systolic (PASP), diastolic (PADP), and mean pulmonary artery pressures (PAMP) were recorded. Cardiac output (CO) was determined using the thermodilution method. Additionally, valvulo-arterial impedance (Zva), cardiac index (CI), and left ventricular stroke work index (LVSWI) were calculated. Aortic valve area (AVA) was calculated using the Gorlin formula.
2.4. Statistics Continuous variables are described as means and standard deviations or medians and interquartile range (IQR), as appropriate, and compared by t-tests if the data were approximately normally distributed and Wilcoxon's rank-sum test otherwise. Categorical data are described with absolute and relative frequencies and compared by the Fisher's exact test. A stepwise binary logistic regression analysis, including all variables with a p-value b0.05 in the univariate analysis, was used to determine predictors of the occurrence of a new CAVB requiring PPM implantation after TAVI. The following three variables were included in the multivariable model: arterial hypertension, atrial fibrillation, and tricuspid regurgitation ≥II. All p-values are two-sided. A p-value b0.05 was considered statistically significant. Statistical analyses were performed with IBM Statistical Package for Social Sciences, version 20.0.0 (SPSS, Inc., Chicago, Illinois).
3. Results 3.1. Patients Comorbidities and baseline characteristics are summarized in Table 1. The average patient age was 81.2 ± 6.9 years and mean logistic EuroSCORE was 22.2 ± 14.1%. 318 (56.5%) of the patients were female. 61 of 563 (10.8%) patients developed a new CAVB after TAVI and were in need in implantation of a PPM either during the TAVI procedure or a few days after. Similar prevalences of comorbidities were documented in all patients, except arterial hypertension, which occurred more often in patients without new PPM while atrial fibrillation was seen less often in that subgroup. Analysis of echocardiographic parameters showed a significant difference in the occurrence of baseline moderate to severe TR (No PPM vs. New PPM: 29.3% vs. 47.5%; p = 0.005). Also, the diameter of the left atrium (LA) was statistically increased in patients with new PPM (No PPM vs. New PPM: 46.3 ± 6.3 vs. 48.8 ± 6.7 mm; p = 0.009). There were no more differences in echocardiographic parameters and biomarkers at baseline between both groups (sup. Table 1).
Fig. 1. A) Patient flow chart. Abbreviations: AS = aortic stenosis; AVB = atrioventricular block; CA = conduction abnormalities; LBBB = left bundle branch block; PPM = permanent pacemaker; RBBB = right bundle branch block; TAVI = transcatheter aortic valve replacement. B) Incidence of complete atrioventricular block (CAVB) after TAVI according to the severity of tricuspid regurgitation (TR).
Please cite this article as: D. Schewel, et al., Correlation of tricuspid regurgitation and new pacemaker implantation in patients undergoing transcatheter aortic valve implantati..., Int J Cardiol (2017), https://doi.org/10.1016/j.ijcard.2018.03.030
D. Schewel et al. / International Journal of Cardiology xxx (2017) xxx–xxx Table 1 Demographic data at baseline.
Male gender Age (years) BMI (kg/cm2) Logistic EuroSCORE (%) EuroSCORE II (%) STS PROM (%) Arterial hypertension Coronary artery disease Porcelain aorta Previous cardiac surgery Impaired renal functiona Hemodialysis Hyperlipidemia Diabetes mellitus Atrial fibrillation Peripheral vascular disease COPD Pulmonary hypertensionb History of stroke
All patients (n = 563)
No PPM (n = 502)
New PPM (n = 61)
p
245 (43.5) 81.2 ± 6.9 26.1 ± 5.2 22.2 ± 14.1 6.3 ± 4.2 5.0 [3.4–8.0] 476 (84.5) 338 (60.0) 67 (11.9) 60 (10.7) 170 (30.2) 15 (2.7) 221 (39.3) 172 (30.6) 259 (46.0) 93 (16.5) 103 (18.3) 111 (19.7) 86 (15.3)
219 (43.6) 81.0 ± 6.9 26.1 ± 5.2 20.3 ± 14.2 6.3 ± 4.1 4.9 [3.3–7.8] 430 (85.7) 305 (60.8) 63 (12.5) 55 (11.0) 156 (31.1) 12 (2.4) 204 (40.6) 156 (31.1) 223 (44.4) 85 (16.9) 91 (18.1) 94 (18.7) 74 (14.7)
26 (42.6) 82.4 ± 7.3 25.9 ± 5.2 19.9 ± 12.9 6.5 ± 4.4 5.2 [3.8–8.5] 46 (75.4) 33 (54.1) 4 (6.6) 5 (8.2) 14 (23.0) 3 (4.9) 17 (27.9) 16 (26.2) 36 (59.0) 8 (13.1) 12 (19.7) 17 (27.9) 12 (19.7)
0.892 0.132 0.750 0.856 0.719 0.835 0.041 0.335 0.212 0.698 0.237 0.390 0.070 0.466 0.041 0.476 0.861 0.122 0.345
All data are mean ± SD, median [interquartile range] or n (%). Abbreviations: BMI = body mass index; COPD = chronic obstructive pulmonary disease; EuroSCORE = European System for Cardiac Operative Risk Evaluation; STS PROM = Society of Thoracic Surgeons Predicted Risk of Mortality. a Glomerular filtration rate b 60 mL/min/1.73 m2. b Pulmonary systolic arterial pressure ≥ 60 mm Hg.
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There were no significant differences neither in acute and 1-year mortality nor in the prevalence of stroke, valve related dysfunction, or acute kidney injury between the two patient groups after TAVI. Only life threatening or disabling bleedings occurred more frequently in patients with new PPM implantation after TAVI (No PPM vs. New PPM: 3.4% vs. 9.8%; p = 0.029; Table 2). 3.3. Tricuspid regurgitation (TR) Patients with new PPM came up with significantly higher prevalence of moderate to severe TR at baseline (no PPM vs. PPM: 29.3% vs. 47.5%; p = 0.005; sup. Table 1). Patients with at least moderate TR were at a twofold higher risk to develop a complete permanent heart block (OR 2.05; 95% CI 1.18–3.55; p = 0.010; sup. Table 2). Fig. 1B demonstrates that the higher the degree of the TR at baseline, the higher the incidence of new persisting CAVB after TAVI. As shown in the supplemental sup. Table 3, higher levels of TR were associated with increased prevalence of MR ≥ II, LA diameter, LVESD, LVEDD, E/E' ratio, and decreased LVEF, thickness of the IVS, PW, and TAPSE at baseline. Correspondingly, NT-proBNP levels were significantly higher in patients with more severe TR. Moreover, elevated LVEDP, systolic and mean PAP, PCWP, RAP, Zva, as well as decreased CO, and CI were documented in the hemodynamic assessments in patients with pronounced severity of the baseline TR. 4. Discussion
3.2. Acute procedural and mid-term outcomes The TAVI procedures were performed either via a transapical (n = 50; 8.9%) or a transvascular (n = 513; 91.1%) approach (transfemoral: n = 490 (87.1%); transaxillary: n = 14 (2.4%); direct transaortic: n = 9 (1.6%)). Acute device success was achieved in 542 (96.3%) patients (Table 2). Acute pericardial tamponade occurred in nine patients due to rupture of the aortic annulus (n = 4) or the ventricular wall (n = 5). Three of these patients were lost during the TAVI procedure. A surgical thoracotomy was performed in five of the nine patients during the same procedure; one of these patients was in need of a second prosthesis. Additionally, in 6 patients (2.3%) a second prosthesis was implanted. In 1 more patient (0.2%), the mean aortic valve gradient was N20 mm Hg after TAVI. Significant valve regurgitation (≥grade 2) was documented in 5 more patients at the end of the TAVI procedure.
In the present study, we aim to investigate further predictors for injury of the atrioventricular conduction system during TAVI with the focus on hemodynamic conditions. To avoid bios by preexisting RBBB, PPM, previously implanted valve prostheses, and urgent conditions, we have excluded these patients from the present study. In result we gain more insight into hemodynamic context of tricuspid regurgitation and development of new conduction abnormalities after TAVI. The main findings are: 1. Significant TR is a frequent finding in patients with late-stage aortic valve stenosis; 2. TR is accompanied by increased left and right ventricular overload; 3. TR seems to be an important predictor for new CAVB after TAVI.
Table 2 Outcomes according to the Valve Academic Research Consortium II (VARC-II) criteria.
Device success Acute device success Absence of immediate procedural mortality Conversion to open heart surgery during TAVR Mean aortic valve gradient N20 mm Hg Moderate or severe prosthetic valve regurgitation Correct positioning of one prosthetic valve Safety at discharge All-cause mortality All stroke Acute kidney injury (stage 2/3) Major vascular complication Minor vascular complication Life threatening or disabling bleeding Major bleeding Coronary obstruction requiring intervention Valve-related dysfunction requiring repeated procedure Clinical efficacy at 1 year All-cause mortality NYHA functional class III and IV All stroke
All patients (n = 563)
No PPM (n = 502)
New PPM (n = 61)
p
542 (96.3) 560 (99.5) 5 (1.0) 1 (0.2) 5 (0.9) 556 (98.8)
485 (96.6) 499 (99.4) 4 (0.9) 0 (0.0) 5 (1.0) 497 (99.0)
57 (93.4) 61 (100) 1 (1.7) 1 (1.7) 0 (0.0) 59 (96.7)
0.567 1.000 1.000 0.175 0.652 0.176
28 (5.0) 28 (5.0) 32 (5.7) 21 (3.7) 67 (11.9) 23 (4.1) 72 (12.8) 0 (0.0) 0 (0.0)
27 (5.4) 24 (4.8) 31 (6.2) 19 (3.8) 58 (11.6) 17 (3.4) 65 (12.9) 0 (0.0) 0 (0.0)
1 (1.6) 4 (6.8) 1 (1.8) 2 (3.3) 9 (14.8) 6 (9.8) 7 (11.5) 0 (0.0) 0 (0.0)
0.241 0.522 0.234 1.000 0.528 0.029 0.842 1.000 1.000
64/320 (20.0) 83/374 (22.2) 29 (5.2)
59/285 (20.7) 63/293 (21.5) 24 (4.8)
5/35 (14.3) 20/81 (24.7) 5 (8.2)
0.503 0.548 0.109
All data are n (%). NYHA = New York Heart Association.
Please cite this article as: D. Schewel, et al., Correlation of tricuspid regurgitation and new pacemaker implantation in patients undergoing transcatheter aortic valve implantati..., Int J Cardiol (2017), https://doi.org/10.1016/j.ijcard.2018.03.030
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D. Schewel et al. / International Journal of Cardiology xxx (2017) xxx–xxx
4. New PPM implantation has no impact on survival or stroke rate in patients after TAVI; Previous studies reported PPM rates between 0 and 12% after implantation of a balloon-expandable prosthesis (e.g. ES) [11–13,27] or self-expanding prosthesis (e.g. MCV: 18–49%) [13]. It should be mentioned that in previous studies patients were included regardless of the presence of conduction abnormalities at baseline. In the present analysis, only patients receiving a balloon-expandable prosthesis and without RBBB at baseline were included. A complete heart block was documented in 10.8% of these patients. Patients with new PPM implantation showed no difference regarding survival in comparison to patients without a new complete heart block after TAVI, as have been described previously by Urena et al. [15]. Interestingly, for the first time, we documented that severe TR at baseline is more often accompanied by a greater incidence of CAVB compared with lower levels of TR. To understand these findings, it is important to understand the concomitance of TR and AS. Previous studies already described the pathophysiologic context of functional TR due to left heart failure from myocardial or valvular causes [28,29]. During the course of the disease, severe AS, due to the increased valvular resistance, firstly leads to increased preload and afterload of the left ventricle (Fig. 2). Further, dilatation of LV and LA, with increased LVEDP and PCWP, results. Level of NT-proBNP, as a surrogate parameter of LV stress, increases correspondingly while LVEF and CI decrease consequently. Because of LV dilatation, MR increases leading to worsening of pulmonary hypertension and right ventricular overload. RAP increases and the RV function decreases. RV overload leads to right heart dilatation and results in progressive functional TR. Thereby, more severe TR seems to be a companion of a more advanced stage of the AS disease. Tverskaya et al. analyzed the effect of LV and RV overload on the conduction system by ligature-narrowing of the ascending aorta or pulmonary artery trunk on guinea pigs. The authors found interstitial edema, focal lesions, and hemorrhages in overloaded ventricles. Moreover, they could demonstrate that LV and RV overload leads to histoenzymological changes in the conducting cardiomyocytes of both
ventricles and the ventricular septum [30,31]. Dilatation of the ventricles and distension of the myocardium are important factors leading to damage of the conduction system and development of new conduction abnormalities. Therefore, patients with chronic AS, who might be in a more progressed stage of LV and RV disease, are suspected to have a pre-damaged conduction system and to be more prone to new higher degree conduction abnormalities if undergoing TAVI. In conclusion, we suspect severe TR to be the result of late-stage chronic AS and a significant predictive factor for developing a new complete heart block after TAVI. 4.1. Limitations Several limitations of the present study have to be regarded. It is a retrospective, single-center, non-randomized, observational study. Prospective studies with longer follow-up are needed to gain more detailed knowledge about the prognostic value of TR as a predictor for new complete heart block and a marker of late-stage aortic disease and/or ventricular overload. Furthermore, it would be helpful to make cytoand histomorphological analyses of conduction cardiomyocytes to gain more insight into the pathophysiologic aspects of valvular disease and heart failure with global ventricular overload. Finally, we have not analyzed evaluated anatomical considerations, valve calcification pattern, implantation depth, and Prosthesis/annulus mismatch, which are known predictors of new CA and PPM after TAVI.
5. Conclusions Permanent pacemaker implantation is a frequent complication in patients with severe AS undergoing TAVI. Increasing severity of TR seems to be a consequence of left and right ventricular overload caused by severe AS and to be an important predictor for new persistent complete heart block requiring pacemaker implantation after TAVI. These patients should receive even more attention to avoid procedural factors that could favor mechanical stress, resulting in permanent pacemaker dependency.
Fig. 2. Pathophysiologic consequences of severe aortic stenosis. Abbreviations: AS = aortic stenosis; LVEDD = left ventricular end-diastolic diameter; LVEDP = left ventricular enddiastolic pressure; LVEF = left ventricular ejection fraction; LVESD = left ventricular end-systolic diameter; LVSWI = left ventricular stroke work index; MR = mitral regurgitation; BNP = brain natriuretic peptide; PAP = pulmonary artery pressure; PCWP = pulmonary capillary wedge pressure; RAP = right atrial pressure; TAPSE = tricuspid annular plane systolic excursion; TR = tricuspid regurgitation; Zva = valvuloarterial impedance.
Please cite this article as: D. Schewel, et al., Correlation of tricuspid regurgitation and new pacemaker implantation in patients undergoing transcatheter aortic valve implantati..., Int J Cardiol (2017), https://doi.org/10.1016/j.ijcard.2018.03.030
D. Schewel et al. / International Journal of Cardiology xxx (2017) xxx–xxx
5.1. Impact on daily practice To avoid new permanent pacemaker implantation in patients undergoing TAVI, it is necessary to know the potential risk factors. Increasing severity of TR seems to be an important predictor for new persistent complete heart block requiring pacemaker implantation after TAVI. These patients should receive even more attention to avoid procedural factors that could favor mechanical irritation.
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Conflict of interest statement Dr. Christian Frerker has received lecture honoraria from Edwards Lifesciences Inc., Dr. Dimitry Schewel, Dr. Jury Schewel, and Dr. Tobias Schmidt have received travel support from Edwards Lifesciences Inc. The other authors have no financial interests in any products or companies described in this article.
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International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Correlation of tricuspid regurgitation and new pacemaker implantation in patients undergoing transcatheter aortic valve implantation Dimitry Schewel a,⁎, Jury Schewel a, Michael Schlüter b, Felix Kreidel a, Tobias Schmidt a, Michael Schmoeckel c, Albrecht Elsässer d, Karl-Heinz Kuck a, Christian Frerker a a
Asklepios Klinik St. Georg, Department of Cardiology, Hamburg, Germany Asklepios proresearch, Hamburg, Germany Asklepios Klinik St. Georg, Department of Cardiac surgery, Hamburg, Germany d Klinikum Oldenburg AöR, Department of Cardiology, Oldenburg, Germany b c
a r t i c l e
i n f o
Article history: Received 10 October 2017 Received in revised form 6 February 2018 Accepted 6 March 2018 Available online xxxx Keywords: TAVI Conduction abnormality Tricuspid regurgitation Aortic valve stenosis Ventricular overload Pacemaker
a b s t r a c t Aims: Conduction abnormalities (CA), in particular complete atrioventricular block (CAVB), requiring permanent pacemaker (PPM) implantation, are frequent complications after transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis (AS). However, the potential mechanisms are still incompletely understood. The objective of this retrospective study was to determine further predictors of CAVB after TAVI in patients without the known predictors. Methods and results: This study included patients without prior CA/PPM who underwent TAVI of a balloonexpandable valve (Sapien or Sapien XT or Sapien 3). Of 563 patients (81.2 ± 6.9 years, 245 men [43.5%], logistic EuroSCORE 22.2 ± 14.1%, STS PROM 5.9 [3.4–8.0]) who were treated by TAVI at our institution between July 2008 and January 2016, 61 (10.8%) developed a permanent CAVB after the procedure. In a multivariable logistic regression analysis moderate/severe tricuspid regurgitation (TR) (OR 2.05; 95% CI 1.18–3.55; p = 0.010) was identified as an independent predictor for new CAVB after TAVI. Moreover, patients with more pronounced TR presented with increased left and right ventricular overload (left ventricular (LV) end-diastolic diameter, LV end-diastolic pressure), pulmonary pressures, NT-proBNP, and prevalence of mitral regurgitation ≥II, whereas LV ejection fraction, TAPSE and cardiac output were decreased. Conclusions: PPM implantation is a frequent complication in patients undergoing TAVI. Increasing severity of TR seems to be a consequence of left and right ventricular overload caused by severe AS and is a significant predictor of new CAVB after TAVI. Condensed abstract: Conduction abnormalities (CA) requiring permanent pacemaker (PPM) implantation, are frequent complications after transcatheter aortic valve implantation (TAVI). This study included patients without prior CA/PPM who underwent TAVI. Of 563 patients 61 (10.8%) developed a permanent CAVB after the procedure. In a multivariable logistic regression analysis moderate/severe tricuspid regurgitation (TR) (OR 2.05; 95% CI 1.18–3.55; p = 0.010) was identified as an independent predictor for new CAVB. Therefore, in patients with moderate/severe TR utmost care should be taken to avoid procedural factors conducive to mechanical irritation of the conduction system, resulting in pacemaker dependency. © 2017 Elsevier B.V. All rights reserved.
1. Introduction Transcatheter aortic valve implantation (TAVI) is preferable recommended in high- and intermediate surgical risk patients with symptomatic severe aortic stenosis (AS) [1–6]. Injury of the conduction system is a known complication of TAVI procedures. As the atrioventricular (AV) conduction system is anatomically close to the aortic valve complex, any ⁎ Corresponding author at: Department of Cardiology, Asklepios Klinik St. Georg, Lohmühlenstr. 5, 20099 Hamburg, Germany. E-mail address: [email protected] (D. Schewel).
mechanical irritation could result in conduction abnormalities, particularly left bundle branch block (LBBB) or complete atrioventricular block (CAVB) requiring a permanent pacemaker (PPM) implantation [7–12]. The incidence of PPM implantations after TAVI has been reported to be 0–12% in balloon-expandable prostheses (e.g. Edwards Sapien) [11–13] and 18–49% in self-expanding prostheses (e.g. Medtronic CoreValve) [13]. Previous studies have shown that PPM implantation does not have an effect on survival after TAVI [14,15]. Nevertheless, it is associated with increased length of hospital stay and higher costs [8,16]. Furthermore, new PPM implantation could result in reduced left ventricular function recovery [7,17] due to impaired AV synchrony
https://doi.org/10.1016/j.ijcard.2018.03.030 0167-5273/© 2017 Elsevier B.V. All rights reserved.
Please cite this article as: D. Schewel, et al., Correlation of tricuspid regurgitation and new pacemaker implantation in patients undergoing transcatheter aortic valve implantati..., Int J Cardiol (2017), https://doi.org/10.1016/j.ijcard.2018.03.030
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by right ventricular pacing [18]. Previous studies have described different predictors for new PPM such as implantation depth [11,19], prosthesis oversizing [11], access route [12], device selection [12], and preexisting right bundle branch block (RBBB) [12]. The aim of this retrospective study was to analyze patients without the known predictors and to find additional independent prognostic factors for new PPM after TAVI of a balloon expandable valve. 2. Methods 2.1. Patient population and study design A total of 1328 patients with severe AS underwent TAVI at our hospital between July 2008 and January 2016. Patients with pre-existed PPM (n = 155) or RBBB (n = 65), patients who underwent emergency TAVI (n = 44), and those with degenerated biological aortic prosthesis (n = 59) were excluded from this analysis. Additionally, only patients who received an Edwards Sapien (n = 25, 4.4%), Sapien XT (n = 251, 44.6%) or Sapien 3 (n = 287, 51%) prosthesis were included. Thereby, 563 patients treated with a balloonexpandable valve were included in the final retrospective analysis. These patients were divided into two groups according to the need for a new PPM after TAVI (no PPM vs. new PPM: 502 (89.2%) vs. 61 (10.8%); Fig. 1A). 2.2. TAVI procedure Indication for aortic valve replacement was the presence of severe, symptomatic AS with an aortic valve area ≤ 1.0 cm2 (≤0.6 cm2/m2) as determined by echocardiography. The patients' operative risk was assessed by calculation of the logistic EuroSCORE and the Society of Thoracic Surgeons predicted risk of mortality (STS PROM). A “Heart Team” consisting of an interventional cardiologist, a cardiac surgeon, and an anesthesiologist evaluated candidates and did the final decision for TAVI procedures. Pre-procedural screening was done by transthoracic and transesophageal echocardiography (annulus diameter, annular morphology, amount of valvular calcification), left heart catheterization, aortic root angiography, and peripheral vascular angiography for evaluation of the aortic annulus (diameter) and the access route. Written informed consent was obtained from all patients. TAVI procedures have been described previously [20,21]. Outcome parameters were assessed according to the Valve Academic Research Consortium (VARC)-2 criteria [22]. Follow-up was scheduled at 30 days and 12 months after discharge. 2.3. Data collection and definitions The patients' functional capacity, as defined by the New York Heart Association (NYHA), was documented before TAVI and at each follow-up visit. Laboratory parameters (N-terminal pro-brain natriuretic peptide [NT-proBNP], creatinine, glomerular filtration rate [GFR], and blood urea nitrogen [BUN]) were collected at baseline. NT-proBNP was measured by a chemoluminescence immunoassay (e411, Roche Diagnostics GmbH, Grenzach-Wyhlen, Germany). The estimated GFR was calculated via the CKD-EPI formula [23]. All patients underwent an extended transthoracic echocardiographic examination by different operators including assessment of aortic valve with mean transvalvular pressure gradient (Pmean), aortic peak velocity (Aortic Vmax) and aortic valve area (AVA) via the continuity equation, severity of regurgitation (AR), left ventricular ejection fraction (LVEF), and severity of mitral regurgitation (MR) and tricuspid regurgitation (TR). Grading of MR and TR was based on an integrated approach of the current European guidelines
[24–26] and graded as 0 (none), I (mild), II (moderate), and III (severe). Furthermore, left atrial diameter (LA), left ventricular end-systolic (LVESD) and end-diastolic diameters (LVEDD), thickness of the interventricular septum (IVS) and left ventricular posterior wall (PW), as well as the ratio of mitral peak velocity of early filling (E) to early diastolic mitral annular velocity (E') as a parameter of diastolic function (E/E' ratio), and tricuspid annular plane systolic excursion (TAPSE) were documented. A 7Fr Swan-Ganz catheter (Edwards Lifesciences, Irvine, CA, USA) was routinely used for hemodynamic measurements during the procedure before and after deployment of the prosthesis. Right atrial pressure (RAP), pulmonary capillary wedge pressure (PCWP), systolic (PASP), diastolic (PADP), and mean pulmonary artery pressures (PAMP) were recorded. Cardiac output (CO) was determined using the thermodilution method. Additionally, valvulo-arterial impedance (Zva), cardiac index (CI), and left ventricular stroke work index (LVSWI) were calculated. Aortic valve area (AVA) was calculated using the Gorlin formula.
2.4. Statistics Continuous variables are described as means and standard deviations or medians and interquartile range (IQR), as appropriate, and compared by t-tests if the data were approximately normally distributed and Wilcoxon's rank-sum test otherwise. Categorical data are described with absolute and relative frequencies and compared by the Fisher's exact test. A stepwise binary logistic regression analysis, including all variables with a p-value b0.05 in the univariate analysis, was used to determine predictors of the occurrence of a new CAVB requiring PPM implantation after TAVI. The following three variables were included in the multivariable model: arterial hypertension, atrial fibrillation, and tricuspid regurgitation ≥II. All p-values are two-sided. A p-value b0.05 was considered statistically significant. Statistical analyses were performed with IBM Statistical Package for Social Sciences, version 20.0.0 (SPSS, Inc., Chicago, Illinois).
3. Results 3.1. Patients Comorbidities and baseline characteristics are summarized in Table 1. The average patient age was 81.2 ± 6.9 years and mean logistic EuroSCORE was 22.2 ± 14.1%. 318 (56.5%) of the patients were female. 61 of 563 (10.8%) patients developed a new CAVB after TAVI and were in need in implantation of a PPM either during the TAVI procedure or a few days after. Similar prevalences of comorbidities were documented in all patients, except arterial hypertension, which occurred more often in patients without new PPM while atrial fibrillation was seen less often in that subgroup. Analysis of echocardiographic parameters showed a significant difference in the occurrence of baseline moderate to severe TR (No PPM vs. New PPM: 29.3% vs. 47.5%; p = 0.005). Also, the diameter of the left atrium (LA) was statistically increased in patients with new PPM (No PPM vs. New PPM: 46.3 ± 6.3 vs. 48.8 ± 6.7 mm; p = 0.009). There were no more differences in echocardiographic parameters and biomarkers at baseline between both groups (sup. Table 1).
Fig. 1. A) Patient flow chart. Abbreviations: AS = aortic stenosis; AVB = atrioventricular block; CA = conduction abnormalities; LBBB = left bundle branch block; PPM = permanent pacemaker; RBBB = right bundle branch block; TAVI = transcatheter aortic valve replacement. B) Incidence of complete atrioventricular block (CAVB) after TAVI according to the severity of tricuspid regurgitation (TR).
Please cite this article as: D. Schewel, et al., Correlation of tricuspid regurgitation and new pacemaker implantation in patients undergoing transcatheter aortic valve implantati..., Int J Cardiol (2017), https://doi.org/10.1016/j.ijcard.2018.03.030
D. Schewel et al. / International Journal of Cardiology xxx (2017) xxx–xxx Table 1 Demographic data at baseline.
Male gender Age (years) BMI (kg/cm2) Logistic EuroSCORE (%) EuroSCORE II (%) STS PROM (%) Arterial hypertension Coronary artery disease Porcelain aorta Previous cardiac surgery Impaired renal functiona Hemodialysis Hyperlipidemia Diabetes mellitus Atrial fibrillation Peripheral vascular disease COPD Pulmonary hypertensionb History of stroke
All patients (n = 563)
No PPM (n = 502)
New PPM (n = 61)
p
245 (43.5) 81.2 ± 6.9 26.1 ± 5.2 22.2 ± 14.1 6.3 ± 4.2 5.0 [3.4–8.0] 476 (84.5) 338 (60.0) 67 (11.9) 60 (10.7) 170 (30.2) 15 (2.7) 221 (39.3) 172 (30.6) 259 (46.0) 93 (16.5) 103 (18.3) 111 (19.7) 86 (15.3)
219 (43.6) 81.0 ± 6.9 26.1 ± 5.2 20.3 ± 14.2 6.3 ± 4.1 4.9 [3.3–7.8] 430 (85.7) 305 (60.8) 63 (12.5) 55 (11.0) 156 (31.1) 12 (2.4) 204 (40.6) 156 (31.1) 223 (44.4) 85 (16.9) 91 (18.1) 94 (18.7) 74 (14.7)
26 (42.6) 82.4 ± 7.3 25.9 ± 5.2 19.9 ± 12.9 6.5 ± 4.4 5.2 [3.8–8.5] 46 (75.4) 33 (54.1) 4 (6.6) 5 (8.2) 14 (23.0) 3 (4.9) 17 (27.9) 16 (26.2) 36 (59.0) 8 (13.1) 12 (19.7) 17 (27.9) 12 (19.7)
0.892 0.132 0.750 0.856 0.719 0.835 0.041 0.335 0.212 0.698 0.237 0.390 0.070 0.466 0.041 0.476 0.861 0.122 0.345
All data are mean ± SD, median [interquartile range] or n (%). Abbreviations: BMI = body mass index; COPD = chronic obstructive pulmonary disease; EuroSCORE = European System for Cardiac Operative Risk Evaluation; STS PROM = Society of Thoracic Surgeons Predicted Risk of Mortality. a Glomerular filtration rate b 60 mL/min/1.73 m2. b Pulmonary systolic arterial pressure ≥ 60 mm Hg.
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There were no significant differences neither in acute and 1-year mortality nor in the prevalence of stroke, valve related dysfunction, or acute kidney injury between the two patient groups after TAVI. Only life threatening or disabling bleedings occurred more frequently in patients with new PPM implantation after TAVI (No PPM vs. New PPM: 3.4% vs. 9.8%; p = 0.029; Table 2). 3.3. Tricuspid regurgitation (TR) Patients with new PPM came up with significantly higher prevalence of moderate to severe TR at baseline (no PPM vs. PPM: 29.3% vs. 47.5%; p = 0.005; sup. Table 1). Patients with at least moderate TR were at a twofold higher risk to develop a complete permanent heart block (OR 2.05; 95% CI 1.18–3.55; p = 0.010; sup. Table 2). Fig. 1B demonstrates that the higher the degree of the TR at baseline, the higher the incidence of new persisting CAVB after TAVI. As shown in the supplemental sup. Table 3, higher levels of TR were associated with increased prevalence of MR ≥ II, LA diameter, LVESD, LVEDD, E/E' ratio, and decreased LVEF, thickness of the IVS, PW, and TAPSE at baseline. Correspondingly, NT-proBNP levels were significantly higher in patients with more severe TR. Moreover, elevated LVEDP, systolic and mean PAP, PCWP, RAP, Zva, as well as decreased CO, and CI were documented in the hemodynamic assessments in patients with pronounced severity of the baseline TR. 4. Discussion
3.2. Acute procedural and mid-term outcomes The TAVI procedures were performed either via a transapical (n = 50; 8.9%) or a transvascular (n = 513; 91.1%) approach (transfemoral: n = 490 (87.1%); transaxillary: n = 14 (2.4%); direct transaortic: n = 9 (1.6%)). Acute device success was achieved in 542 (96.3%) patients (Table 2). Acute pericardial tamponade occurred in nine patients due to rupture of the aortic annulus (n = 4) or the ventricular wall (n = 5). Three of these patients were lost during the TAVI procedure. A surgical thoracotomy was performed in five of the nine patients during the same procedure; one of these patients was in need of a second prosthesis. Additionally, in 6 patients (2.3%) a second prosthesis was implanted. In 1 more patient (0.2%), the mean aortic valve gradient was N20 mm Hg after TAVI. Significant valve regurgitation (≥grade 2) was documented in 5 more patients at the end of the TAVI procedure.
In the present study, we aim to investigate further predictors for injury of the atrioventricular conduction system during TAVI with the focus on hemodynamic conditions. To avoid bios by preexisting RBBB, PPM, previously implanted valve prostheses, and urgent conditions, we have excluded these patients from the present study. In result we gain more insight into hemodynamic context of tricuspid regurgitation and development of new conduction abnormalities after TAVI. The main findings are: 1. Significant TR is a frequent finding in patients with late-stage aortic valve stenosis; 2. TR is accompanied by increased left and right ventricular overload; 3. TR seems to be an important predictor for new CAVB after TAVI.
Table 2 Outcomes according to the Valve Academic Research Consortium II (VARC-II) criteria.
Device success Acute device success Absence of immediate procedural mortality Conversion to open heart surgery during TAVR Mean aortic valve gradient N20 mm Hg Moderate or severe prosthetic valve regurgitation Correct positioning of one prosthetic valve Safety at discharge All-cause mortality All stroke Acute kidney injury (stage 2/3) Major vascular complication Minor vascular complication Life threatening or disabling bleeding Major bleeding Coronary obstruction requiring intervention Valve-related dysfunction requiring repeated procedure Clinical efficacy at 1 year All-cause mortality NYHA functional class III and IV All stroke
All patients (n = 563)
No PPM (n = 502)
New PPM (n = 61)
p
542 (96.3) 560 (99.5) 5 (1.0) 1 (0.2) 5 (0.9) 556 (98.8)
485 (96.6) 499 (99.4) 4 (0.9) 0 (0.0) 5 (1.0) 497 (99.0)
57 (93.4) 61 (100) 1 (1.7) 1 (1.7) 0 (0.0) 59 (96.7)
0.567 1.000 1.000 0.175 0.652 0.176
28 (5.0) 28 (5.0) 32 (5.7) 21 (3.7) 67 (11.9) 23 (4.1) 72 (12.8) 0 (0.0) 0 (0.0)
27 (5.4) 24 (4.8) 31 (6.2) 19 (3.8) 58 (11.6) 17 (3.4) 65 (12.9) 0 (0.0) 0 (0.0)
1 (1.6) 4 (6.8) 1 (1.8) 2 (3.3) 9 (14.8) 6 (9.8) 7 (11.5) 0 (0.0) 0 (0.0)
0.241 0.522 0.234 1.000 0.528 0.029 0.842 1.000 1.000
64/320 (20.0) 83/374 (22.2) 29 (5.2)
59/285 (20.7) 63/293 (21.5) 24 (4.8)
5/35 (14.3) 20/81 (24.7) 5 (8.2)
0.503 0.548 0.109
All data are n (%). NYHA = New York Heart Association.
Please cite this article as: D. Schewel, et al., Correlation of tricuspid regurgitation and new pacemaker implantation in patients undergoing transcatheter aortic valve implantati..., Int J Cardiol (2017), https://doi.org/10.1016/j.ijcard.2018.03.030
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4. New PPM implantation has no impact on survival or stroke rate in patients after TAVI; Previous studies reported PPM rates between 0 and 12% after implantation of a balloon-expandable prosthesis (e.g. ES) [11–13,27] or self-expanding prosthesis (e.g. MCV: 18–49%) [13]. It should be mentioned that in previous studies patients were included regardless of the presence of conduction abnormalities at baseline. In the present analysis, only patients receiving a balloon-expandable prosthesis and without RBBB at baseline were included. A complete heart block was documented in 10.8% of these patients. Patients with new PPM implantation showed no difference regarding survival in comparison to patients without a new complete heart block after TAVI, as have been described previously by Urena et al. [15]. Interestingly, for the first time, we documented that severe TR at baseline is more often accompanied by a greater incidence of CAVB compared with lower levels of TR. To understand these findings, it is important to understand the concomitance of TR and AS. Previous studies already described the pathophysiologic context of functional TR due to left heart failure from myocardial or valvular causes [28,29]. During the course of the disease, severe AS, due to the increased valvular resistance, firstly leads to increased preload and afterload of the left ventricle (Fig. 2). Further, dilatation of LV and LA, with increased LVEDP and PCWP, results. Level of NT-proBNP, as a surrogate parameter of LV stress, increases correspondingly while LVEF and CI decrease consequently. Because of LV dilatation, MR increases leading to worsening of pulmonary hypertension and right ventricular overload. RAP increases and the RV function decreases. RV overload leads to right heart dilatation and results in progressive functional TR. Thereby, more severe TR seems to be a companion of a more advanced stage of the AS disease. Tverskaya et al. analyzed the effect of LV and RV overload on the conduction system by ligature-narrowing of the ascending aorta or pulmonary artery trunk on guinea pigs. The authors found interstitial edema, focal lesions, and hemorrhages in overloaded ventricles. Moreover, they could demonstrate that LV and RV overload leads to histoenzymological changes in the conducting cardiomyocytes of both
ventricles and the ventricular septum [30,31]. Dilatation of the ventricles and distension of the myocardium are important factors leading to damage of the conduction system and development of new conduction abnormalities. Therefore, patients with chronic AS, who might be in a more progressed stage of LV and RV disease, are suspected to have a pre-damaged conduction system and to be more prone to new higher degree conduction abnormalities if undergoing TAVI. In conclusion, we suspect severe TR to be the result of late-stage chronic AS and a significant predictive factor for developing a new complete heart block after TAVI. 4.1. Limitations Several limitations of the present study have to be regarded. It is a retrospective, single-center, non-randomized, observational study. Prospective studies with longer follow-up are needed to gain more detailed knowledge about the prognostic value of TR as a predictor for new complete heart block and a marker of late-stage aortic disease and/or ventricular overload. Furthermore, it would be helpful to make cytoand histomorphological analyses of conduction cardiomyocytes to gain more insight into the pathophysiologic aspects of valvular disease and heart failure with global ventricular overload. Finally, we have not analyzed evaluated anatomical considerations, valve calcification pattern, implantation depth, and Prosthesis/annulus mismatch, which are known predictors of new CA and PPM after TAVI.
5. Conclusions Permanent pacemaker implantation is a frequent complication in patients with severe AS undergoing TAVI. Increasing severity of TR seems to be a consequence of left and right ventricular overload caused by severe AS and to be an important predictor for new persistent complete heart block requiring pacemaker implantation after TAVI. These patients should receive even more attention to avoid procedural factors that could favor mechanical stress, resulting in permanent pacemaker dependency.
Fig. 2. Pathophysiologic consequences of severe aortic stenosis. Abbreviations: AS = aortic stenosis; LVEDD = left ventricular end-diastolic diameter; LVEDP = left ventricular enddiastolic pressure; LVEF = left ventricular ejection fraction; LVESD = left ventricular end-systolic diameter; LVSWI = left ventricular stroke work index; MR = mitral regurgitation; BNP = brain natriuretic peptide; PAP = pulmonary artery pressure; PCWP = pulmonary capillary wedge pressure; RAP = right atrial pressure; TAPSE = tricuspid annular plane systolic excursion; TR = tricuspid regurgitation; Zva = valvuloarterial impedance.
Please cite this article as: D. Schewel, et al., Correlation of tricuspid regurgitation and new pacemaker implantation in patients undergoing transcatheter aortic valve implantati..., Int J Cardiol (2017), https://doi.org/10.1016/j.ijcard.2018.03.030
D. Schewel et al. / International Journal of Cardiology xxx (2017) xxx–xxx
5.1. Impact on daily practice To avoid new permanent pacemaker implantation in patients undergoing TAVI, it is necessary to know the potential risk factors. Increasing severity of TR seems to be an important predictor for new persistent complete heart block requiring pacemaker implantation after TAVI. These patients should receive even more attention to avoid procedural factors that could favor mechanical irritation.
[12]
[13]
[14]
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Conflict of interest statement Dr. Christian Frerker has received lecture honoraria from Edwards Lifesciences Inc., Dr. Dimitry Schewel, Dr. Jury Schewel, and Dr. Tobias Schmidt have received travel support from Edwards Lifesciences Inc. The other authors have no financial interests in any products or companies described in this article.
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Please cite this article as: D. Schewel, et al., Correlation of tricuspid regurgitation and new pacemaker implantation in patients undergoing transcatheter aortic valve implantati..., Int J Cardiol (2017), https://doi.org/10.1016/j.ijcard.2018.03.030