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Prognostic Value of QRS Duration After Transcatheter Aortic Valve Implantation for Aortic Stenosis Using the CoreValve
Prognostic Value of QRS Duration After Transcatheter Aortic Valve Implantation for Aortic Stenosis Using the CoreValve Kentaro Meguro, MDa,b,*, Nicolas Lellouche, MDa, Masanori Yamamoto, MDa, Emilie Fougeres, MDa, Jean-Luc Monin, MDa, Pascal Lim, MDa, Gauthier Mouillet, MDa, Jean-Luc Dubois-Rande, MDa, and Emmanuel Teiger, MDa Transcatheter aortic valve implantation (TAVI) is effective in treating severe aortic stenosis in high-risk surgical patients. We evaluated the value of the QRS duration (QRSd) in predicting the mid-term morbidity and mortality after TAVI. We conducted a prospective cohort study of 91 consecutive patients who underwent TAVI using the CoreValve at our teaching hospital cardiology unit in 2008 to 2010 who survived to hospital discharge; 57% were women, and their mean age was 84 – 7 years. The QRSd at discharge was used to classify the patients into 3 groups: QRSd £120 ms, n [ 18 (20%); QRSd >120 ms but £150 ms, n [ 30 (33%); and QRSd >150 ms, n [ 43 (47%). We used 2 end points: (1) all-cause mortality and (2) all-cause mortality or admission for heart failure. After a median of 12 months, the normal-QRSd patients showed a trend toward, or had, significantly better overall survival and survival free of admission for heart failure compared with the intermediate-QRSd group (p [ 0.084 and p [ 0.002, respectively) and the long-QRSd group (p [ 0.015 and p [ 0.001, respectively). The factors significantly associated with all-cause mortality were the Society of Thoracic Surgeons score, aortic valve area, post-TAVI dilation, acute kidney injury, hospital days after TAVI, and QRSd at discharge. On multivariate analysis, QRSd was the strongest independent predictor of all-cause mortality (hazard ratio 1.036, 95% confidence interval 1.016 to 1.056; p <0.001) and allcause mortality or heart failure admission (hazard ratio 1.025, 95% confidence interval 1.011 to 1.039; p <0.001). The other independent predictors were the Society of Thoracic Surgeons score, acute kidney injury, and post-TAVI hospital days. In conclusion, a longer QRSd after TAVI was associated with greater morbidity and mortality after 12 months. The QRSd at discharge independently predicted mortality and morbidity after TAVI. Ó 2013 Elsevier Inc. All rights reserved. (Am J Cardiol 2013;111:1778e1783)
Transcatheter aortic valve implantation (TAVI) is effective in high-risk surgical patients with severe symptomatic aortic stenosis. TAVI has been reported to improve hemodynamic aortic valve function and survival.1e4 However, heart conduction abnormalities are common after TAVI. More specifically, new left bundle branch block (LBBB) develops in approximately 30% of patients5e8 and requires permanent pacemaker implantation in 1/3 of patients after TAVI.5,9e12 Although it was recently reported that TAVIinduced LBBB was an independent predictor of mortality recently,13 the importance of the QRS duration (QRSd) is still unclear. The objective of the present prospective cohort study was to evaluate the prognostic significance of QRSd at hospital discharge on morbidity and mortality after CoreValve (Medtronic, Novi, Minnesota) implantation.
a Interventional Cardiology Unit, Henri Mondor University Hospital, Val-de-Marne University, Creteil, France; and bDepartment of Cardiology, Edogawa Hospital, Tokyo, Japan. Manuscript received September 10, 2012; revised manuscript received and accepted February 17, 2013. See page 1782 for disclosure information. *Corresponding author: Tel: (þ81) 3-3673-1221; fax: (þ81) 3-36731229. E-mail address: [email protected] (K. Meguro).
0002-9149/13/$ - see front matter Ó 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2013.02.032
Methods We prospectively enrolled consecutive patients who had undergone TAVI using the CoreValve at our teaching hospital (Henri Mondor, Créteil, France) from December 2007 to December 2010. The patients were enrolled if they were at high surgical risk, as defined by a logistic European System for Cardiac Operative Risk Evaluation score >15%, or were considered ineligible for open chest cardiac surgery by 2 independent cardiac surgeons. Our institutional review board approved the study, and all patients provided written informed consent before study inclusion. The technical aspects of the TAVI procedure using the CoreValve system (Medtronic) have been previously described in detail.3,4 For each patient, an electrocardiogram was recorded before TAVI, just after TAVI, and just before hospital discharge, using a standard digital recorder with 12 simultaneous leads and a 25-mm/s speed. The QRSd was calculated as the mean of all QRSd values in the 12 leads. Using the QRSd value before discharge, the patients were classified into 3 groups: QRSd 120 ms (normal), QRSd from 120 to 150 ms (intermediate), and QRSd >150 ms (long; Figure 1).14 Data on the clinical events, including death and admission for heart failure (HF), were collected by our center 1, 3, 6, 12, and 24 months after TAVI. The follow-up duration www.ajconline.org
Valvular Heart Disease/Importance of QRS Duration After CoreValve TAVI 104 patients underwent TAVI between December 2007 and December 2010
4 patients with Edwards Sapien Valve were excluded 9 patients died before discharge and were excluded
91 patients for the study analysis
n=18 (20%) (QRSd≤120 ms)
n=30 (33%) (120 ms
n=43 (47%) (QRSd>150 ms)
Figure 1. Flow chart of patient enrollment. We divided the enrolled patients into 3 groups according to their QRSd at hospital discharge.
was 3 months in all patients. We used 2 end points to evaluate the prognostic value of QRSd: death from any cause and either death from any cause or admission for HF. The data are presented as the mean SD if normally distributed and the median (interquartile range) otherwise. To compare the continuous variables across the groups, we used Student’s t test or analysis of variance with the Tukey post hoc test. Fisher’s exact test was used to compare the categorical variables. Survival curves for the time-to-event variables were constructed using all available follow-up data with Kaplan-Meier estimates and were compared using the log-rank test. The parameters significantly associated with either evaluation end point (all-cause death or either allcause death or HF admission) on univariate analysis using Student’s t test or Fisher’s exact test, with p <0.05, were entered into a multivariate Cox proportional hazards model using forward stepwise selection. The variables associated with p <0.05 in the multivariate model were considered to independently predict the relevant evaluation criterion. All statistical analyses were done using the Statistical Package for Social Sciences, version 19 (SPSS, Chicago, Illinois). Results Of the 104 patients who underwent TAVI at our center during the 3-year study period, 100 received the CoreValve system (26-mm diameter in 44 patients and 29-mm diameter in 56 patients). Of the 104 patients, 4, who received the Edwards Sapien valve (Edwards LifeSciences, Irvine, California), and 9, who died before hospital discharge, were excluded from the present study (Figure 1), leaving 91 patients (age 84 7 years) for the analysis. The QRSd was normal before TAVI in 53 patients (58%), just after TAVI in 12 patients (13%), and at hospital discharge in 6 additional patients. Thus, 18 patients were included in the normalQRSd group (120 ms), 30 (33%) in the intermediateQRSd group, and 43 (47%) in the long-QRSd group (Figure 1). The main characteristics of the 3 groups are listed in Table 1. Significant differences were found across the groups in some patient characteristics. The normal-QRSd group had significantly greater severity of aortic valve stenosis, as assessed by the mean aortic gradient and mean aortic valve
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area. No significant differences were found in the procedural characteristics or periprocedural complications. After a median follow-up of 12 months after hospital discharge (interquartile range 6 to 17), no patient in the normal-QRSd group had died. However, 8 (27%) and 16 (37%) patients had died in the intermediate-QRSd and longQRSd group, respectively. The normal-QRSd group had a lower trend of mortality or significantly lower mortality than the other 2 groups (p ¼ 0.084 and p ¼ 0.015, respectively; Figure 2). As shown in Figure 2, the proportion of survivors without an admission for HF was significantly greater in the normal-QRSd group than in the other 2 groups (p ¼ 0.002 and p ¼ 0.001, respectively). Neither allcause mortality nor all-cause mortality/HF admission differed significantly between the intermediate-QRSd and long-QRSd groups. Compared with the survivors, the patients who died had some different characteristics (Table 2). On multivariate analysis, the QRSd at discharge was the strongest independent risk factor for all-cause mortality; the other independent risk factors were the Society of Thoracic Surgeons score, acute kidney injury (AKI), and post-TAVI hospital days (Table 3). During the follow-up period, 40 patients (44%) either died or were admitted for HF. This patient subgroup had a significantly greater proportion of patients with aortic regurgitation grade 2 or greater before TAVI and a greater aortic valve area, rate of AKI, QRSd just after TAVI, and QRSd at hospital discharge compared with the survivors without HF admissions. This patient subgroup also had lower values for the aortic gradient. On multivariate analysis, the QRSd at hospital discharge was independently associated with all-cause mortality/HF admission. Grade 2 or greater aortic regurgitation before TAVI and AKI were also independent risk factors for QRSd (Table 4). Discussion In the present study, we have shown that patients with intermediate or long QRSd at hospital discharge after TAVI using the CoreValve system had greater rates of all-cause mortality and admission for HF compared with the patients with normal QRSd values. The QRSd at hospital discharge was among the strongest independent predictors of all-cause mortality and all-cause mortality/HF admission after TAVI. Electrical conduction disturbances are common after TAVI. In previous studies, LBBB developed in 3% to 45% of patients after TAVI5e8 and required permanent pacing in 1/3 of cases after TAVI.5,9e12 In our study, only 18 patients (20%) had normal QRSd values at hospital discharge. Several factors can explain the discrepancy between our results and those from earlier studies. First, the QRSd was not measured accurately in these studies, which might, therefore, have underestimated the rate of conduction disturbances. Second, in our study, only 53 patients (58%) had normal QRSd values before TAVI compared with 70% to 90% in previous studies.5,8e10 Third, our study population received the CoreValve, which has been reported to be associated with greater rates of conduction disturbances, such as LBBB, and with greater requirements for permanent pacing compared with the Edward Sapiens valve (Edwards LifeSciences).10e12
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Table 1 Baseline and procedural characteristics of the 3 groups defined by QRS duration at hospital discharge Variable
QRSd (ms) 120 (n ¼ 18)
Age (yrs) Women (n) Logistic EuroSCORE (%) STS score (%) COPD (n) Previous MI (n) Previous PCI (n) Previous CABG (n) PPM before TAVI (n) Peripheral artery disease (n) Previous stroke (n) Hemodialysis (n) Serum creatinine (mmol/L) Atrial fibrillation (n) Mean aortic gradient (mm Hg) Aortic valve area (cm2) AR grade 2 before TAVI (n) LVEF (%) LVEF 35% (n) Predilation (n) Postdilation (n) AR grade 2 after TAVI (n) AKI (n) New PPM implantation (n) Admissions after TAVI (n) QRSd before TAVI (ms) QRSd after TAVI (ms) QRSd at discharge (ms)
86.3 5.6 13 (72) 26.7 9.9 13.0 6.9 5 (28) 3 (17) 5 (28) 3 (17) 0 (0) 3 (17) 2 (11) 1 (6) 104 61 6 (33) 63.4 21.9† 0.54 0.18z 0 (0) 49.9 9.7 2 (11) 16 (89) 0 (0) 1 (6) 1 (6) 2 (11) 88 100 13 123 31† 102 12†
>120 to 150 (n ¼ 30) 82.6 9.1 26 (87) 25.4 11.6 13.3 9.2 6 (20) 2 (7) 7 (23) 4 (13) 1 (3) 5 (17) 0 (0) 0 (0) 105 36 14 (47) 43.2 16.4 0.67 0.20 7 (23) 47.7 14.8 8 (27) 26 (87) 4 (13) 0 (0) 3 (10) 3 (10) 96 112 24 141 11† 138 7†
p Value >150 (n ¼ 43) 84.7 6.1 13 (30) 26.4 11.9 12.0 8.3 12 (28) 7 (16) 19 (44) 2 (5) 18 (42) 13 (30) 5 (12) 2 (5) 137 90 23 (54) 42.4 13.4 0.78 0.21 2 (5) 46.2 13.8 12 (28) 37 (86) 6 (14) 5 (12) 11 (27) 14 (33) 10 6 139 35† 167 17† 171 17†
0.193 <0.001* 0.904 0.764 0.773 0.473 0.144 0.247 <0.001* 0.372 0.132 0.432 0.092 0.363 <0.001 <0.001 0.012x 0.613 0.365 1.000 0.330 0.111 0.104 0.049x 0.402 <0.001 <0.001 <0.001
Data are presented as mean SD or n (%). AR ¼ aortic regurgitation; CABG ¼ coronary artery bypass grafting; COPD ¼ chronic obstructive pulmonary disease; EuroSCORE ¼ European System for Cardiac Operative Risk Evaluation; LVEF ¼ left ventricular ejection fraction; MI ¼ myocardial infarction; PCI ¼ percutaneous coronary intervention; PPM ¼ permanent pacemaker; STS ¼ Society of Thoracic Surgeons. * p <0.01. † p <0.01 compared with both of the other groups. z p <0.01 compared with the QRSd >150-ms group with analysis of variance followed by Tukey’s procedure. x p <0.05, Fisher’s exact test.
Figure 2. Event-free curves in the 3 groups defined by QRSd at hospital discharge. (A) Survival curve and (B) curve of survival without admission for HF. Event-free rates were calculated using the Kaplan-Meier method and compared using the log-rank test; p values indicate the probability values for betweengroup comparisons.
Valvular Heart Disease/Importance of QRS Duration After CoreValve TAVI Table 2 Comparisons of characteristics between survivors and nonsurvivors Characteristic Age (yrs) Women (n) Logistic EuroSCORE (%) STS score (%) COPD (n) Previous MI (n) Previous PCI (n) Previous CABG (n) PPM before TAVI (n) Peripheral artery disease (n) Previous stroke (n) Hemodialysis (n) Serum creatinine (mmol/L) Atrial fibrillation (n) Mean aortic gradient (mm Hg) Aortic valve area (cm2) AR grade 2 before TAVI (n) LVEF (%) LVEF 35% (n) Predilation (n) Postdilation (n) AR grade 2 after TAVI (n) AKI (n) New implantation of PPM (n) Admissions after TAVI (n) QRSd before TAVI (ms) QRSd after TAVI (ms) QRSd at discharge (ms)
Nonsurvivors (n ¼ 24)
Survivors (n ¼ 67)
p Value
84.8 7.3 10 (42) 30.4 14.3 16.0 8.5 8 (33) 3 (13) 8 (33) 1 (4) 6 (25) 5 (21) 3 (13) 1 (4) 137 86 14 (58) 41.3 13.7 0.79 0.22 4 (17) 48.3 13.5 6 (25) 20 (83) 6 (25) 3 (13) 8 (35) 7 (29) 13 8 128 34 156 22 159 20
84.2 7.2 42 (63) 24.6 9.8 11.4 8.0 15 (22) 9 (13) 23 (34) 8 (12) 13 (19) 16 (24) 4 (6) 2 (3) 114 66 29 (43) 48.8 19.2 0.66 0.21 5 (8) 47.1 13.4 16 (24) 59 (88) 4 (6) 3 (5) 7 (11) 12 (18) 85 120 32 148 27 142 31
0.735 0.094 0.076 0.021* 0.290 1.000 1.000 0.436 0.568 1.000 0.375 1.000 0.187 0.239 0.079 0.010* 0.236 0.696 1.000 0.726 0.019† 0.185 0.020† 0.255 0.002z 0.262 0.165 0.002z
Data are presented as mean SD or n (%). Abbreviations as in Table 1. * p <0.05, Student’s t test. † p <0.05, Fisher’s exact test. z p <0.01, Student’s t test. Table 3 Significant predictors of all-cause mortality by multivariate analysis Variable
HR (Multivariate) (95% CI)
STS score (per point) AKI Admissions after TAVI (per day) QRSd at discharge (per ms)
1.075 5.229 1.079 1.036
(1.019e1.134) (1.881e14.538) (1.017e1.145) (1.016e1.056)
p Value 0.008 0.002 0.012 <0.001
CI ¼ confidence interval; HR ¼ hazard ratio; other abbreviations as in Table 1. Table 4 Multivariate predictors of all-cause mortality and/or admission for heart failure (HF) Variable AR grade 2 before TAVI AKI QRSd at discharge (per ms)
HR (Multivariate) (95% CI)
p Value
3.573 (1.495e8.541) 3.358 (1.600e7.046) 1.025 (1.011e1.039)
0.004 0.001 <0.001
Abbreviations as in Tables 1 and 3.
Although the reasons for the greater rate of conduction disturbances with CoreValve are unclear, the shape of the CoreValve device might result in greater pressure on the septum compared with the Edwards Sapiens valve,10,15
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thereby causing damage to the atrioventricular conduction pathway.10,16 In addition, in patients with aortic valve stenosis, changes in the leaflet structure can decrease the distance between the noncoronary cusp and the atrioventricular node.10 In this situation, expansion of the aortic balloon or prosthesis can injure the atrioventricular conduction pathway by local ischemia and/or direct mechanical pressure. Furthermore, anatomic factors, such as deeper prosthesis implantation and greater septal thickness, might increase the risk of atrioventricular conduction block.6,8,15,17 QRSd is well established as a strong independent predictor of morbidity and mortality in patients with HF.18e20 Also, after surgical aortic valve replacement, conduction disturbances have been independently associated with an increased risk of adverse cardiac events, such as sudden cardiac death, syncope, and new-onset atrioventricular nodal block.21,22 It has also been reported that all-cause mortality after TAVI was greater in patients who developed LBBB than in patients who did not.13 In our study, patients with a normal QRSd (120 ms) at hospital discharge had significantly better survival and survival free of HF admission compared with patients with a longer QRSd. These results are consistent with those from previous studies about the QRSd in patients with HF.14,18e20 It is reasonable to assume that conduction disturbances contribute to deteriorate left ventricular function by inducing mechanical dyssynchrony, most notably in patients with preexisting left ventricular dysfunction.19,23 Interventions capable of decreasing the risk of QRSd prolongation after TAVI need to be developed. Deeper prosthesis implantation has been reported to be a major risk factor for post-TAVI QRSd prolongation. Consequently, new technologies designed to optimize valve positioning hold promise for improving patient outcomes after TAVI.6,8 It was also reported that the learning curve might affect the frequency of LBBB development after CoreValve implantation.13 Cardiac resynchronization therapy is a proven treatment for symptomatic patients with systolic HF and QRSd prolongation.24e27 In our cohort, 20 patients (22%) had both impaired left ventricular function after TAVI (ejection fraction 35%) and QRSd prolongation and might, therefore, have been good candidates for cardiac resynchronization therapy.28 Additional investigations are required to validate this hypothesis. Previous studies have investigated the factors associated with in-hospital mortality. However, these were factors directly related to the procedure itself, such as conversion to open heart surgery, cardiac tamponade, and vascular complications.3 The reported predictors of midterm mortality have included previous stroke, postprocedural aortic regurgitation leak, and AKI.3,29,30 We excluded patients who died before discharge, because most in-hospital deaths have been thought to be related to the TAVI procedure itself. In the remaining patients, the QRSd at discharge was the strongest independent predictor of both all-cause mortality and all-cause mortality/HF admission in the medium term. Previous studies have shown that previous stroke and postprocedural aortic regurgitation predicted both morbidity and mortality.3,30 Neither factor was significantly associated with our evaluation criteria, perhaps because of our
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limited number of patients compared with those in former studies. Our study had several limitations. First, it was done at a single center. However, our sample size was comparable to that of several previous studies.18 A larger multicenter study is needed to confirm the prognostic significance of the QRSd after TAVI. Second, the best time for QRSd measurement after TAVI remains unclear. It has been reported that newly developed LBBB after TAVI resolves within 30 days in about 1/2 of cases.6,8 In our study, of the 41 patients with a normal QRSd before TAVI and an abnormal QRSd just after TAVI, only 6 (15%) had improvements in their conduction disturbances before hospital discharge. However, the electrocardiographic data 30 days after TAVI were not available for all our patients and, consequently, were not analyzed. Disclosures
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Valvular Heart Disease/Importance of QRS Duration After CoreValve TAVI Sirnes PA, Tendera M, Vardas P, Widimsky P, Tendera M, Anker SD, Blanc JJ, Gasparini M, Hoes AW, Israel CW, Kalarus Z, Merkely B, Swedberg K, Camm AJ. 2010 Focused update of ESC guidelines on device therapy in heart failure: an update of the 2008 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure and the 2007 ESC guidelines for cardiac and resynchronization therapy: developed with the special contribution of the Heart Failure Association and the European Heart Rhythm Association. Europace 2010;12: 1526e1536. 26. Moss AJ, Hall WJ, Cannom DS, Klein H, Brown MW, Daubert JP, Estes NA III, Foster E, Greenberg H, Higgins SL, Pfeffer MA, Solomon SD, Wilber D, Zareba W. Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med 2009;361: 1329e1338. 27. Tang AS, Wells GA, Talajic M, Arnold MO, Sheldon R, Connolly S, Hohnloser SH, Nichol G, Birnie DH, Sapp JL, Yee R, Healey JS,
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Rouleau JL. Cardiac-resynchronization therapy for mild-to-moderate heart failure. N Engl J Med 2010;363:2385e2395. 28. Meguro K, Lellouche N, Teiger E. Cardiac resynchronization therapy improved heart failure after left bundle branch block during transcatheter aortic valve implantation. J Invasive Cardiol 2012;24:132e133. 29. Bagur R, Webb JG, Nietlispach F, Dumont E, De Larochelliere R, Doyle D, Masson JB, Gutierrez MJ, Clavel MA, Bertrand OF, Pibarot P, Rodes-Cabau J. Acute kidney injury following transcatheter aortic valve implantation: predictive factors, prognostic value, and comparison with surgical aortic valve replacement. Eur Heart J 2010;31:865e874. 30. Abdel-Wahab M, Zahn R, Horack M, Gerckens U, Schuler G, Sievert H, Eggebrecht H, Senges J, Richardt G. Aortic regurgitation after transcatheter aortic valve implantation: incidence and early outcome: results from the German transcatheter aortic valve interventions registry. Heart 2011;97:899e906.
Transcatheter aortic valve implantation (TAVI) is effective in high-risk surgical patients with severe symptomatic aortic stenosis. TAVI has been reported to improve hemodynamic aortic valve function and survival.1e4 However, heart conduction abnormalities are common after TAVI. More specifically, new left bundle branch block (LBBB) develops in approximately 30% of patients5e8 and requires permanent pacemaker implantation in 1/3 of patients after TAVI.5,9e12 Although it was recently reported that TAVIinduced LBBB was an independent predictor of mortality recently,13 the importance of the QRS duration (QRSd) is still unclear. The objective of the present prospective cohort study was to evaluate the prognostic significance of QRSd at hospital discharge on morbidity and mortality after CoreValve (Medtronic, Novi, Minnesota) implantation.
a Interventional Cardiology Unit, Henri Mondor University Hospital, Val-de-Marne University, Creteil, France; and bDepartment of Cardiology, Edogawa Hospital, Tokyo, Japan. Manuscript received September 10, 2012; revised manuscript received and accepted February 17, 2013. See page 1782 for disclosure information. *Corresponding author: Tel: (þ81) 3-3673-1221; fax: (þ81) 3-36731229. E-mail address: [email protected] (K. Meguro).
0002-9149/13/$ - see front matter Ó 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2013.02.032
Methods We prospectively enrolled consecutive patients who had undergone TAVI using the CoreValve at our teaching hospital (Henri Mondor, Créteil, France) from December 2007 to December 2010. The patients were enrolled if they were at high surgical risk, as defined by a logistic European System for Cardiac Operative Risk Evaluation score >15%, or were considered ineligible for open chest cardiac surgery by 2 independent cardiac surgeons. Our institutional review board approved the study, and all patients provided written informed consent before study inclusion. The technical aspects of the TAVI procedure using the CoreValve system (Medtronic) have been previously described in detail.3,4 For each patient, an electrocardiogram was recorded before TAVI, just after TAVI, and just before hospital discharge, using a standard digital recorder with 12 simultaneous leads and a 25-mm/s speed. The QRSd was calculated as the mean of all QRSd values in the 12 leads. Using the QRSd value before discharge, the patients were classified into 3 groups: QRSd 120 ms (normal), QRSd from 120 to 150 ms (intermediate), and QRSd >150 ms (long; Figure 1).14 Data on the clinical events, including death and admission for heart failure (HF), were collected by our center 1, 3, 6, 12, and 24 months after TAVI. The follow-up duration www.ajconline.org
Valvular Heart Disease/Importance of QRS Duration After CoreValve TAVI 104 patients underwent TAVI between December 2007 and December 2010
4 patients with Edwards Sapien Valve were excluded 9 patients died before discharge and were excluded
91 patients for the study analysis
n=18 (20%) (QRSd≤120 ms)
n=30 (33%) (120 ms
n=43 (47%) (QRSd>150 ms)
Figure 1. Flow chart of patient enrollment. We divided the enrolled patients into 3 groups according to their QRSd at hospital discharge.
was 3 months in all patients. We used 2 end points to evaluate the prognostic value of QRSd: death from any cause and either death from any cause or admission for HF. The data are presented as the mean SD if normally distributed and the median (interquartile range) otherwise. To compare the continuous variables across the groups, we used Student’s t test or analysis of variance with the Tukey post hoc test. Fisher’s exact test was used to compare the categorical variables. Survival curves for the time-to-event variables were constructed using all available follow-up data with Kaplan-Meier estimates and were compared using the log-rank test. The parameters significantly associated with either evaluation end point (all-cause death or either allcause death or HF admission) on univariate analysis using Student’s t test or Fisher’s exact test, with p <0.05, were entered into a multivariate Cox proportional hazards model using forward stepwise selection. The variables associated with p <0.05 in the multivariate model were considered to independently predict the relevant evaluation criterion. All statistical analyses were done using the Statistical Package for Social Sciences, version 19 (SPSS, Chicago, Illinois). Results Of the 104 patients who underwent TAVI at our center during the 3-year study period, 100 received the CoreValve system (26-mm diameter in 44 patients and 29-mm diameter in 56 patients). Of the 104 patients, 4, who received the Edwards Sapien valve (Edwards LifeSciences, Irvine, California), and 9, who died before hospital discharge, were excluded from the present study (Figure 1), leaving 91 patients (age 84 7 years) for the analysis. The QRSd was normal before TAVI in 53 patients (58%), just after TAVI in 12 patients (13%), and at hospital discharge in 6 additional patients. Thus, 18 patients were included in the normalQRSd group (120 ms), 30 (33%) in the intermediateQRSd group, and 43 (47%) in the long-QRSd group (Figure 1). The main characteristics of the 3 groups are listed in Table 1. Significant differences were found across the groups in some patient characteristics. The normal-QRSd group had significantly greater severity of aortic valve stenosis, as assessed by the mean aortic gradient and mean aortic valve
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area. No significant differences were found in the procedural characteristics or periprocedural complications. After a median follow-up of 12 months after hospital discharge (interquartile range 6 to 17), no patient in the normal-QRSd group had died. However, 8 (27%) and 16 (37%) patients had died in the intermediate-QRSd and longQRSd group, respectively. The normal-QRSd group had a lower trend of mortality or significantly lower mortality than the other 2 groups (p ¼ 0.084 and p ¼ 0.015, respectively; Figure 2). As shown in Figure 2, the proportion of survivors without an admission for HF was significantly greater in the normal-QRSd group than in the other 2 groups (p ¼ 0.002 and p ¼ 0.001, respectively). Neither allcause mortality nor all-cause mortality/HF admission differed significantly between the intermediate-QRSd and long-QRSd groups. Compared with the survivors, the patients who died had some different characteristics (Table 2). On multivariate analysis, the QRSd at discharge was the strongest independent risk factor for all-cause mortality; the other independent risk factors were the Society of Thoracic Surgeons score, acute kidney injury (AKI), and post-TAVI hospital days (Table 3). During the follow-up period, 40 patients (44%) either died or were admitted for HF. This patient subgroup had a significantly greater proportion of patients with aortic regurgitation grade 2 or greater before TAVI and a greater aortic valve area, rate of AKI, QRSd just after TAVI, and QRSd at hospital discharge compared with the survivors without HF admissions. This patient subgroup also had lower values for the aortic gradient. On multivariate analysis, the QRSd at hospital discharge was independently associated with all-cause mortality/HF admission. Grade 2 or greater aortic regurgitation before TAVI and AKI were also independent risk factors for QRSd (Table 4). Discussion In the present study, we have shown that patients with intermediate or long QRSd at hospital discharge after TAVI using the CoreValve system had greater rates of all-cause mortality and admission for HF compared with the patients with normal QRSd values. The QRSd at hospital discharge was among the strongest independent predictors of all-cause mortality and all-cause mortality/HF admission after TAVI. Electrical conduction disturbances are common after TAVI. In previous studies, LBBB developed in 3% to 45% of patients after TAVI5e8 and required permanent pacing in 1/3 of cases after TAVI.5,9e12 In our study, only 18 patients (20%) had normal QRSd values at hospital discharge. Several factors can explain the discrepancy between our results and those from earlier studies. First, the QRSd was not measured accurately in these studies, which might, therefore, have underestimated the rate of conduction disturbances. Second, in our study, only 53 patients (58%) had normal QRSd values before TAVI compared with 70% to 90% in previous studies.5,8e10 Third, our study population received the CoreValve, which has been reported to be associated with greater rates of conduction disturbances, such as LBBB, and with greater requirements for permanent pacing compared with the Edward Sapiens valve (Edwards LifeSciences).10e12
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Table 1 Baseline and procedural characteristics of the 3 groups defined by QRS duration at hospital discharge Variable
QRSd (ms) 120 (n ¼ 18)
Age (yrs) Women (n) Logistic EuroSCORE (%) STS score (%) COPD (n) Previous MI (n) Previous PCI (n) Previous CABG (n) PPM before TAVI (n) Peripheral artery disease (n) Previous stroke (n) Hemodialysis (n) Serum creatinine (mmol/L) Atrial fibrillation (n) Mean aortic gradient (mm Hg) Aortic valve area (cm2) AR grade 2 before TAVI (n) LVEF (%) LVEF 35% (n) Predilation (n) Postdilation (n) AR grade 2 after TAVI (n) AKI (n) New PPM implantation (n) Admissions after TAVI (n) QRSd before TAVI (ms) QRSd after TAVI (ms) QRSd at discharge (ms)
86.3 5.6 13 (72) 26.7 9.9 13.0 6.9 5 (28) 3 (17) 5 (28) 3 (17) 0 (0) 3 (17) 2 (11) 1 (6) 104 61 6 (33) 63.4 21.9† 0.54 0.18z 0 (0) 49.9 9.7 2 (11) 16 (89) 0 (0) 1 (6) 1 (6) 2 (11) 88 100 13 123 31† 102 12†
>120 to 150 (n ¼ 30) 82.6 9.1 26 (87) 25.4 11.6 13.3 9.2 6 (20) 2 (7) 7 (23) 4 (13) 1 (3) 5 (17) 0 (0) 0 (0) 105 36 14 (47) 43.2 16.4 0.67 0.20 7 (23) 47.7 14.8 8 (27) 26 (87) 4 (13) 0 (0) 3 (10) 3 (10) 96 112 24 141 11† 138 7†
p Value >150 (n ¼ 43) 84.7 6.1 13 (30) 26.4 11.9 12.0 8.3 12 (28) 7 (16) 19 (44) 2 (5) 18 (42) 13 (30) 5 (12) 2 (5) 137 90 23 (54) 42.4 13.4 0.78 0.21 2 (5) 46.2 13.8 12 (28) 37 (86) 6 (14) 5 (12) 11 (27) 14 (33) 10 6 139 35† 167 17† 171 17†
0.193 <0.001* 0.904 0.764 0.773 0.473 0.144 0.247 <0.001* 0.372 0.132 0.432 0.092 0.363 <0.001 <0.001 0.012x 0.613 0.365 1.000 0.330 0.111 0.104 0.049x 0.402 <0.001 <0.001 <0.001
Data are presented as mean SD or n (%). AR ¼ aortic regurgitation; CABG ¼ coronary artery bypass grafting; COPD ¼ chronic obstructive pulmonary disease; EuroSCORE ¼ European System for Cardiac Operative Risk Evaluation; LVEF ¼ left ventricular ejection fraction; MI ¼ myocardial infarction; PCI ¼ percutaneous coronary intervention; PPM ¼ permanent pacemaker; STS ¼ Society of Thoracic Surgeons. * p <0.01. † p <0.01 compared with both of the other groups. z p <0.01 compared with the QRSd >150-ms group with analysis of variance followed by Tukey’s procedure. x p <0.05, Fisher’s exact test.
Figure 2. Event-free curves in the 3 groups defined by QRSd at hospital discharge. (A) Survival curve and (B) curve of survival without admission for HF. Event-free rates were calculated using the Kaplan-Meier method and compared using the log-rank test; p values indicate the probability values for betweengroup comparisons.
Valvular Heart Disease/Importance of QRS Duration After CoreValve TAVI Table 2 Comparisons of characteristics between survivors and nonsurvivors Characteristic Age (yrs) Women (n) Logistic EuroSCORE (%) STS score (%) COPD (n) Previous MI (n) Previous PCI (n) Previous CABG (n) PPM before TAVI (n) Peripheral artery disease (n) Previous stroke (n) Hemodialysis (n) Serum creatinine (mmol/L) Atrial fibrillation (n) Mean aortic gradient (mm Hg) Aortic valve area (cm2) AR grade 2 before TAVI (n) LVEF (%) LVEF 35% (n) Predilation (n) Postdilation (n) AR grade 2 after TAVI (n) AKI (n) New implantation of PPM (n) Admissions after TAVI (n) QRSd before TAVI (ms) QRSd after TAVI (ms) QRSd at discharge (ms)
Nonsurvivors (n ¼ 24)
Survivors (n ¼ 67)
p Value
84.8 7.3 10 (42) 30.4 14.3 16.0 8.5 8 (33) 3 (13) 8 (33) 1 (4) 6 (25) 5 (21) 3 (13) 1 (4) 137 86 14 (58) 41.3 13.7 0.79 0.22 4 (17) 48.3 13.5 6 (25) 20 (83) 6 (25) 3 (13) 8 (35) 7 (29) 13 8 128 34 156 22 159 20
84.2 7.2 42 (63) 24.6 9.8 11.4 8.0 15 (22) 9 (13) 23 (34) 8 (12) 13 (19) 16 (24) 4 (6) 2 (3) 114 66 29 (43) 48.8 19.2 0.66 0.21 5 (8) 47.1 13.4 16 (24) 59 (88) 4 (6) 3 (5) 7 (11) 12 (18) 85 120 32 148 27 142 31
0.735 0.094 0.076 0.021* 0.290 1.000 1.000 0.436 0.568 1.000 0.375 1.000 0.187 0.239 0.079 0.010* 0.236 0.696 1.000 0.726 0.019† 0.185 0.020† 0.255 0.002z 0.262 0.165 0.002z
Data are presented as mean SD or n (%). Abbreviations as in Table 1. * p <0.05, Student’s t test. † p <0.05, Fisher’s exact test. z p <0.01, Student’s t test. Table 3 Significant predictors of all-cause mortality by multivariate analysis Variable
HR (Multivariate) (95% CI)
STS score (per point) AKI Admissions after TAVI (per day) QRSd at discharge (per ms)
1.075 5.229 1.079 1.036
(1.019e1.134) (1.881e14.538) (1.017e1.145) (1.016e1.056)
p Value 0.008 0.002 0.012 <0.001
CI ¼ confidence interval; HR ¼ hazard ratio; other abbreviations as in Table 1. Table 4 Multivariate predictors of all-cause mortality and/or admission for heart failure (HF) Variable AR grade 2 before TAVI AKI QRSd at discharge (per ms)
HR (Multivariate) (95% CI)
p Value
3.573 (1.495e8.541) 3.358 (1.600e7.046) 1.025 (1.011e1.039)
0.004 0.001 <0.001
Abbreviations as in Tables 1 and 3.
Although the reasons for the greater rate of conduction disturbances with CoreValve are unclear, the shape of the CoreValve device might result in greater pressure on the septum compared with the Edwards Sapiens valve,10,15
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thereby causing damage to the atrioventricular conduction pathway.10,16 In addition, in patients with aortic valve stenosis, changes in the leaflet structure can decrease the distance between the noncoronary cusp and the atrioventricular node.10 In this situation, expansion of the aortic balloon or prosthesis can injure the atrioventricular conduction pathway by local ischemia and/or direct mechanical pressure. Furthermore, anatomic factors, such as deeper prosthesis implantation and greater septal thickness, might increase the risk of atrioventricular conduction block.6,8,15,17 QRSd is well established as a strong independent predictor of morbidity and mortality in patients with HF.18e20 Also, after surgical aortic valve replacement, conduction disturbances have been independently associated with an increased risk of adverse cardiac events, such as sudden cardiac death, syncope, and new-onset atrioventricular nodal block.21,22 It has also been reported that all-cause mortality after TAVI was greater in patients who developed LBBB than in patients who did not.13 In our study, patients with a normal QRSd (120 ms) at hospital discharge had significantly better survival and survival free of HF admission compared with patients with a longer QRSd. These results are consistent with those from previous studies about the QRSd in patients with HF.14,18e20 It is reasonable to assume that conduction disturbances contribute to deteriorate left ventricular function by inducing mechanical dyssynchrony, most notably in patients with preexisting left ventricular dysfunction.19,23 Interventions capable of decreasing the risk of QRSd prolongation after TAVI need to be developed. Deeper prosthesis implantation has been reported to be a major risk factor for post-TAVI QRSd prolongation. Consequently, new technologies designed to optimize valve positioning hold promise for improving patient outcomes after TAVI.6,8 It was also reported that the learning curve might affect the frequency of LBBB development after CoreValve implantation.13 Cardiac resynchronization therapy is a proven treatment for symptomatic patients with systolic HF and QRSd prolongation.24e27 In our cohort, 20 patients (22%) had both impaired left ventricular function after TAVI (ejection fraction 35%) and QRSd prolongation and might, therefore, have been good candidates for cardiac resynchronization therapy.28 Additional investigations are required to validate this hypothesis. Previous studies have investigated the factors associated with in-hospital mortality. However, these were factors directly related to the procedure itself, such as conversion to open heart surgery, cardiac tamponade, and vascular complications.3 The reported predictors of midterm mortality have included previous stroke, postprocedural aortic regurgitation leak, and AKI.3,29,30 We excluded patients who died before discharge, because most in-hospital deaths have been thought to be related to the TAVI procedure itself. In the remaining patients, the QRSd at discharge was the strongest independent predictor of both all-cause mortality and all-cause mortality/HF admission in the medium term. Previous studies have shown that previous stroke and postprocedural aortic regurgitation predicted both morbidity and mortality.3,30 Neither factor was significantly associated with our evaluation criteria, perhaps because of our
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limited number of patients compared with those in former studies. Our study had several limitations. First, it was done at a single center. However, our sample size was comparable to that of several previous studies.18 A larger multicenter study is needed to confirm the prognostic significance of the QRSd after TAVI. Second, the best time for QRSd measurement after TAVI remains unclear. It has been reported that newly developed LBBB after TAVI resolves within 30 days in about 1/2 of cases.6,8 In our study, of the 41 patients with a normal QRSd before TAVI and an abnormal QRSd just after TAVI, only 6 (15%) had improvements in their conduction disturbances before hospital discharge. However, the electrocardiographic data 30 days after TAVI were not available for all our patients and, consequently, were not analyzed. Disclosures
11.
12.
13.
14.
15.
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