Catheterization and Cardiovascular Interventions 84:1007–1012 (2014)
Original Studies Prevalence and Predictors of Carotid Artery Stenosis in Patients With Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation Arie Steinvil,1,2* MD MHA, Eran Leshem-Rubinow,1,2 MD MHA, Yigal Abramowitz,1,2 MD, Yacov Shacham,1,2 MD, Yaron Arbel,1,2 MD, Shmuel Banai,1,2 MD, Natan M. Bornstein,1,2 MD, Ariel Finkelstein,1,2 MD, and Amir Halkin,1,2 MD Objectives: Our aim was to analyze the prevalence and predictors of Carotid artery stenosis (CAS) in patients undergoing transcatheter aortic valve implantation (TAVI). Background: CAS is associated with the risk of periprocedural stroke in patients undergoing cardiac surgery. However, little is known about the prevalence of and clinical significance of CAS in the setting of TAVI. Methods: Consecutive patients undergoing a carotid Doppler study the day before TAVI were followed prospectively. CAS was defined in accordance with current practice guidelines. Logistic regression models were used to identify independent correlates of CAS. Results: The study included 171 patients (age 82 6 6, male gender 47%). Carotid atherosclerosis (CA, defined as any carotid plaque) was present in 164 (96%) of patients, and CAS (peak systolic velocity [PSV] 125 cm/ sec; 50% diameter stenosis) in 57 (33%) patients. Severe CAS (PSV 230 cm/sec; 70% stenosis, or near occlusion) was found in 15 (9%) patients. By multivariate analysis, smoking and a higher Euroscore independently predicted the presence of CAS. Patients in the present TAVI cohort had a significantly higher prevalence of both unilateral and bilateral CAS 50% than those in a previously reported cohort (n 5 494 patients, age 70) undergoing clinically driven coronary angiography (33% vs. 20%, OR 5 1.9, P 5 0.001; and, 13% vs. 6%, OR 5 2.3, P 5 0.003, respectively). CAS was not independently associated with 30-day mortality or stroke rates. Conclusions: The prevalence of CAS in patients undergoing TAVI is high, exceeding that observed in patients undergoing catheterization for coronary indications. The impact of CAS on clinical outcomes following TAVI merits further research. VC 2014 Wiley Periodicals, Inc. Key words: transcatheter valve implantation; carotid artery disease; aortic stenosis 1
INTRODUCTION
Transcatheter aortic valve implantation (TAVI) has emerged as a therapeutic alternative to surgical aortic valve replacement (SAVR) for patients with severe aortic stenosis (AS) deemed at high-risk for open surgical procedures [1,2]. Notwithstanding, ischemic stroke, which complicates TAVI in 3–6% [3], remains an important safety concern. Extra-cranial carotid artery stenosis (CAS) is associated with an enhanced risk of periprocedural stroke in patients undergoing isolated coronary artery bypass surgery [4,5] and possibly isolated aortic valve replacement as well [6]. This association notwithstanding, the C 2014 Wiley Periodicals, Inc. V
Departments of Cardiology and Neurology, Tel-Aviv Medical Center, Tel-Aviv, Israel 2 Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel Conflict of interest: Dr. Ariel Finkelstein receives consultation fees from Medtronic Cardiovascular and Edwards Lifesciences. *Correspondence to: Arie Steinvil, Department of Cardiology, The Tel-Aviv Medical Center, 6 Weizman St. Tel-Aviv, Israel. E-mail: [email protected] Received 5 April 2014; Revision accepted 22 June 2014 DOI: 10.1002/ccd.25585 Published online 10 July (wileyonlinelibrary.com)
2014
in
Wiley
Online
Library
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Steinvil et al.
direct contribution of CAS to the pathogenesis of perioperative adverse neurological outcomes following open cardiac surgery is questionable [5], since most perioperative stroke events are anatomically unrelated to CAS [4]. In TAVI-related stroke, atheroembolism originating from the valve implantation site and/or passage of large-caliber catheters through the aortic arch probably plays a major pathogenetic role [3,7], though hemodynamic compromise during rapid ventricular pacing and valve deployment may also be of importance [8], particularly in patients with obstructive carotid artery disease. Findings from studies in patients undergoing SAVR have differed with respect to the prevalence of significant CAS [6,9,10]. Because the prevalence, predictors, and clinical significance of CAS in patients with severe AS undergoing TAVI have not been systematically evaluated, we performed carotid Duplex ultrasound studies in consecutive patients undergoing TAVI via the transfemoral access route. The prevalence and predictors of CAS were analyzed using current consensus guidelines for the definition of carotid artery disease [11]. MATERIALS AND METHODS Study Population
Study group: between August 2012 and February 2014, 171 consecutive patients underwent percutaneous transfemoral TAVI at our medical center [12]. Informed consent was obtained from each patient as approved by the institutional ethics committee. Patients were recruited as part of their participation in the Tel-Aviv Prospective Angiography Study (TAPAS). [13] The diagnosis of severe AS was based on clinical, echocardiographic, and hemodynamic criteria. Suitability and eligibility for TAVI was determined by a Heart-Team consisting of an interventional cardiologist, a cardiac surgeon, and a senior echocardiographer [14]. Control group: A previously reported cohort of patients undergoing same-day carotid Doppler imaging and clinically indicated coronary angiography served as an historical control group [13], with which comparisons of CAS prevalence were made. TAVI Procedure
Procedural stages have been described in detail previously [12]. Briefly, all patients underwent elective preparatory preprocedural coronary and peripheral angiography. The TAVI procedure was initiated with a contralateral femoral arterial puncture for visualization of the ipsilateral arterial access site and hemostasis purposes. Positioning of temporary transvenous pacemaker in the right ventricular apex and balloon valvulopasty before valve implantation were performed in all patients. One of the
three aortic valve prostheses commercially available throughout the study were used in all patients: The CoreValve prosthesis (Medtronic, MN, USA) in 99, the Sapien XT prosthesis (Edwards Lifesciences, California, USA) in 67, and the Portico Transcatheter Aortic Heart Valve (St. Jude medical, MN, USA) in two patients. Definition of CAS and CAD Carotid Doppler ultrasound was preformed the day before TAVI. Its protocol has been previously described [13]. Briefly, atherosclerosis of both the left and right internal carotid arteries was assessed by an experienced technician blinded to clinical and coronary angiographic data. The internal carotid arteries were scanned using carotid duplex equipment (HD11 XE, Philips healthcare, Andover, MA) with a 3–12 MHz linear-array transducer. Internal CAS was evaluated by the maximum percentage of diameter reduction recorded by B-mode ultrasound, and by the peak systolic and diastolic velocities (PSV and PDV, respectively) per Doppler. Lesion severity was defined as the greatest stenosis observed either on the right or left internal carotid artery. Ultrasound and Doppler findings were classified according to consensus imaging guidelines [11]: normal study (PSV 70% diameter stenosis); total or near occlusion (defined as zero PSV and no visible flow). For the purposes of this study, CAS was defined as any carotid lesion exceeding 50% diameter stenosis, whereas evidence of any atherosclerotic plaque, regardless of lesion severity, was considered as carotid atherosclerosis (designated as CA). Coronary artery lesion severity was determined by visual estimation or by a quantitative coronary angiography program (Xcelera, Philips healthcare, Andover, MA), at the discretion of the interventional cardiologist performing the procedure. Clinically significant CAD was defined as the presence of a coronary lesion resulting in a lumen diameter stenosis of either >70% for the left anterior descending artery, left circumflex artery, right coronary artery, or their major branches; or, >50% in the left main coronary artery[15]. Patients were stratified according to the number of involved vessels as follows: Normal coronaries or nonobstructive CAD (individuals not meeting the criteria for clinically significant CAD), 1VD, 2VD, 3VD (significant lesions in 1, 2, 3 vessels, respectively), and LMD (significant disease of the left main coronary artery, with or without concomitant lesions in other vessels) [15].
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
Carotid Artery Stenosis in TAVI Patients
Statistical Analysis All data are displayed as mean (6standard deviation) for continuous variables, and as the number (percentage) of patients in each group for categorical variables. Significance for continuous variables was determined with the student’s t-test following Levean’s test for homogeneity. Significance for categorical variables was determined with the v2 and Fischer exact tests. Logistic regression models in which CAS (50% stenosis) was the dependant variable were adjusted for variables found to be significant in the univariate models. Analyses were considered significant at a 2-tailed P value of less than 0.05. The SPSS statistical package was used to perform all statistical evaluation (SSPS, Chicago, IL). RESULTS Baseline Features
Baseline demographic, clinical, and procedural characteristics for the study population (n ¼ 171) are presented in Table I. Manifest vascular disease and the presence of comorbidities were frequent (CAD determined angiographically in 60% of patients), with a history of prior stroke in 11% (Table I). Two patients underwent a valve-in-valve procedure. Baseline AVA was 0.7 6 0.2 cm2, whereas mean and peak transvalvar systolic pressure gradients were 47 6 15 and 77 6 23 mm Hg, respectively. Valve implantation was not performed in three patients due to a major vascular complication preceding this procedural stage. Postprocedural mean and peak transvalvar systolic pressure gradients were 9 6 3 and 16 6 7 mm Hg, respectively. Prevalence and Correlates of CAS in TAVI Patients
Doppler evidence of CA and CAS was present in 96% (n ¼ 164) and 33% (n ¼ 57) of TAVI patients, respectively. Univariate correlates of CAS included a history of hypertension, smoking, prior coronary revascularization, a higher STS score or logistic Euroscore, CCT, and the presence of angiographic CAD. By multivariate logistic regression models, smoking history and an increasing Euroscore were identified as independent predictors of CAS (Table II). The prevalence of CAS and CA in the present cohort was compared to that observed in a previously reported cohort of 1,405 patients undergoing carotid Doppler imaging on the day of clinically indicated coronary angiography [13]. Compared to the entire reference cohort (reference group 1 in Table III), TAVI patients had a substantially higher risk of CA, CAS, and severe
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TABLE I. Baseline Study Population Characteristics Total (n ¼ 171) Age, years (mean 6 SD, range) Male gender (n, %) Diabetes Mellitus (n, %) Dyslipidemia (n, %) Hypertension (n, %) Smoking history (n, %) Height (mean 6 SD) Weight (mean 6 SD) BMI (mean 6 SD; Kg/m2) CrCl (mean 6 SD; ml/min) PVD (n, %) Stroke (n, %) Systolic heart failure (n, %) Prior MI Prior CABG Prior PCI AF (any type) (n, %) EF % (mean 6 SD) STS score (mean 6 SD) Euroscore (mean 6 SD) Coronary angiography Normal or nonobstructive One vessel disease Two vessel disease Three vessel disease Left Main disease MCV valve size (n, %) 23 mm 26 mm 29 mm 31 mm ESX valve size (n, %) 23 mm 26 mm 29 mm Portico valve size (n, %) 25 mm Hospitalization days (mean 6 SD)
82 6 6, 61–95 81, 47% 65, 38% 141, 83% 150, 88% 64, 37% 163 6 9 72 6 14 27 6 5 63 6 21 8, 5% 18, 11% 26, 15% 32, 19% 35, 21% 79, 46% 51, 30% 56 6 7 4.4 6 3 18.0 6 13 70, 41% 36, 21% 24, 14% 41, 24% 10, 6% 6, 4% 53, 31% 39, 23% 1,
Original Studies Prevalence and Predictors of Carotid Artery Stenosis in Patients With Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation Arie Steinvil,1,2* MD MHA, Eran Leshem-Rubinow,1,2 MD MHA, Yigal Abramowitz,1,2 MD, Yacov Shacham,1,2 MD, Yaron Arbel,1,2 MD, Shmuel Banai,1,2 MD, Natan M. Bornstein,1,2 MD, Ariel Finkelstein,1,2 MD, and Amir Halkin,1,2 MD Objectives: Our aim was to analyze the prevalence and predictors of Carotid artery stenosis (CAS) in patients undergoing transcatheter aortic valve implantation (TAVI). Background: CAS is associated with the risk of periprocedural stroke in patients undergoing cardiac surgery. However, little is known about the prevalence of and clinical significance of CAS in the setting of TAVI. Methods: Consecutive patients undergoing a carotid Doppler study the day before TAVI were followed prospectively. CAS was defined in accordance with current practice guidelines. Logistic regression models were used to identify independent correlates of CAS. Results: The study included 171 patients (age 82 6 6, male gender 47%). Carotid atherosclerosis (CA, defined as any carotid plaque) was present in 164 (96%) of patients, and CAS (peak systolic velocity [PSV] 125 cm/ sec; 50% diameter stenosis) in 57 (33%) patients. Severe CAS (PSV 230 cm/sec; 70% stenosis, or near occlusion) was found in 15 (9%) patients. By multivariate analysis, smoking and a higher Euroscore independently predicted the presence of CAS. Patients in the present TAVI cohort had a significantly higher prevalence of both unilateral and bilateral CAS 50% than those in a previously reported cohort (n 5 494 patients, age 70) undergoing clinically driven coronary angiography (33% vs. 20%, OR 5 1.9, P 5 0.001; and, 13% vs. 6%, OR 5 2.3, P 5 0.003, respectively). CAS was not independently associated with 30-day mortality or stroke rates. Conclusions: The prevalence of CAS in patients undergoing TAVI is high, exceeding that observed in patients undergoing catheterization for coronary indications. The impact of CAS on clinical outcomes following TAVI merits further research. VC 2014 Wiley Periodicals, Inc. Key words: transcatheter valve implantation; carotid artery disease; aortic stenosis 1
INTRODUCTION
Transcatheter aortic valve implantation (TAVI) has emerged as a therapeutic alternative to surgical aortic valve replacement (SAVR) for patients with severe aortic stenosis (AS) deemed at high-risk for open surgical procedures [1,2]. Notwithstanding, ischemic stroke, which complicates TAVI in 3–6% [3], remains an important safety concern. Extra-cranial carotid artery stenosis (CAS) is associated with an enhanced risk of periprocedural stroke in patients undergoing isolated coronary artery bypass surgery [4,5] and possibly isolated aortic valve replacement as well [6]. This association notwithstanding, the C 2014 Wiley Periodicals, Inc. V
Departments of Cardiology and Neurology, Tel-Aviv Medical Center, Tel-Aviv, Israel 2 Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel Conflict of interest: Dr. Ariel Finkelstein receives consultation fees from Medtronic Cardiovascular and Edwards Lifesciences. *Correspondence to: Arie Steinvil, Department of Cardiology, The Tel-Aviv Medical Center, 6 Weizman St. Tel-Aviv, Israel. E-mail: [email protected] Received 5 April 2014; Revision accepted 22 June 2014 DOI: 10.1002/ccd.25585 Published online 10 July (wileyonlinelibrary.com)
2014
in
Wiley
Online
Library
1008
Steinvil et al.
direct contribution of CAS to the pathogenesis of perioperative adverse neurological outcomes following open cardiac surgery is questionable [5], since most perioperative stroke events are anatomically unrelated to CAS [4]. In TAVI-related stroke, atheroembolism originating from the valve implantation site and/or passage of large-caliber catheters through the aortic arch probably plays a major pathogenetic role [3,7], though hemodynamic compromise during rapid ventricular pacing and valve deployment may also be of importance [8], particularly in patients with obstructive carotid artery disease. Findings from studies in patients undergoing SAVR have differed with respect to the prevalence of significant CAS [6,9,10]. Because the prevalence, predictors, and clinical significance of CAS in patients with severe AS undergoing TAVI have not been systematically evaluated, we performed carotid Duplex ultrasound studies in consecutive patients undergoing TAVI via the transfemoral access route. The prevalence and predictors of CAS were analyzed using current consensus guidelines for the definition of carotid artery disease [11]. MATERIALS AND METHODS Study Population
Study group: between August 2012 and February 2014, 171 consecutive patients underwent percutaneous transfemoral TAVI at our medical center [12]. Informed consent was obtained from each patient as approved by the institutional ethics committee. Patients were recruited as part of their participation in the Tel-Aviv Prospective Angiography Study (TAPAS). [13] The diagnosis of severe AS was based on clinical, echocardiographic, and hemodynamic criteria. Suitability and eligibility for TAVI was determined by a Heart-Team consisting of an interventional cardiologist, a cardiac surgeon, and a senior echocardiographer [14]. Control group: A previously reported cohort of patients undergoing same-day carotid Doppler imaging and clinically indicated coronary angiography served as an historical control group [13], with which comparisons of CAS prevalence were made. TAVI Procedure
Procedural stages have been described in detail previously [12]. Briefly, all patients underwent elective preparatory preprocedural coronary and peripheral angiography. The TAVI procedure was initiated with a contralateral femoral arterial puncture for visualization of the ipsilateral arterial access site and hemostasis purposes. Positioning of temporary transvenous pacemaker in the right ventricular apex and balloon valvulopasty before valve implantation were performed in all patients. One of the
three aortic valve prostheses commercially available throughout the study were used in all patients: The CoreValve prosthesis (Medtronic, MN, USA) in 99, the Sapien XT prosthesis (Edwards Lifesciences, California, USA) in 67, and the Portico Transcatheter Aortic Heart Valve (St. Jude medical, MN, USA) in two patients. Definition of CAS and CAD Carotid Doppler ultrasound was preformed the day before TAVI. Its protocol has been previously described [13]. Briefly, atherosclerosis of both the left and right internal carotid arteries was assessed by an experienced technician blinded to clinical and coronary angiographic data. The internal carotid arteries were scanned using carotid duplex equipment (HD11 XE, Philips healthcare, Andover, MA) with a 3–12 MHz linear-array transducer. Internal CAS was evaluated by the maximum percentage of diameter reduction recorded by B-mode ultrasound, and by the peak systolic and diastolic velocities (PSV and PDV, respectively) per Doppler. Lesion severity was defined as the greatest stenosis observed either on the right or left internal carotid artery. Ultrasound and Doppler findings were classified according to consensus imaging guidelines [11]: normal study (PSV 70% diameter stenosis); total or near occlusion (defined as zero PSV and no visible flow). For the purposes of this study, CAS was defined as any carotid lesion exceeding 50% diameter stenosis, whereas evidence of any atherosclerotic plaque, regardless of lesion severity, was considered as carotid atherosclerosis (designated as CA). Coronary artery lesion severity was determined by visual estimation or by a quantitative coronary angiography program (Xcelera, Philips healthcare, Andover, MA), at the discretion of the interventional cardiologist performing the procedure. Clinically significant CAD was defined as the presence of a coronary lesion resulting in a lumen diameter stenosis of either >70% for the left anterior descending artery, left circumflex artery, right coronary artery, or their major branches; or, >50% in the left main coronary artery[15]. Patients were stratified according to the number of involved vessels as follows: Normal coronaries or nonobstructive CAD (individuals not meeting the criteria for clinically significant CAD), 1VD, 2VD, 3VD (significant lesions in 1, 2, 3 vessels, respectively), and LMD (significant disease of the left main coronary artery, with or without concomitant lesions in other vessels) [15].
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
Carotid Artery Stenosis in TAVI Patients
Statistical Analysis All data are displayed as mean (6standard deviation) for continuous variables, and as the number (percentage) of patients in each group for categorical variables. Significance for continuous variables was determined with the student’s t-test following Levean’s test for homogeneity. Significance for categorical variables was determined with the v2 and Fischer exact tests. Logistic regression models in which CAS (50% stenosis) was the dependant variable were adjusted for variables found to be significant in the univariate models. Analyses were considered significant at a 2-tailed P value of less than 0.05. The SPSS statistical package was used to perform all statistical evaluation (SSPS, Chicago, IL). RESULTS Baseline Features
Baseline demographic, clinical, and procedural characteristics for the study population (n ¼ 171) are presented in Table I. Manifest vascular disease and the presence of comorbidities were frequent (CAD determined angiographically in 60% of patients), with a history of prior stroke in 11% (Table I). Two patients underwent a valve-in-valve procedure. Baseline AVA was 0.7 6 0.2 cm2, whereas mean and peak transvalvar systolic pressure gradients were 47 6 15 and 77 6 23 mm Hg, respectively. Valve implantation was not performed in three patients due to a major vascular complication preceding this procedural stage. Postprocedural mean and peak transvalvar systolic pressure gradients were 9 6 3 and 16 6 7 mm Hg, respectively. Prevalence and Correlates of CAS in TAVI Patients
Doppler evidence of CA and CAS was present in 96% (n ¼ 164) and 33% (n ¼ 57) of TAVI patients, respectively. Univariate correlates of CAS included a history of hypertension, smoking, prior coronary revascularization, a higher STS score or logistic Euroscore, CCT, and the presence of angiographic CAD. By multivariate logistic regression models, smoking history and an increasing Euroscore were identified as independent predictors of CAS (Table II). The prevalence of CAS and CA in the present cohort was compared to that observed in a previously reported cohort of 1,405 patients undergoing carotid Doppler imaging on the day of clinically indicated coronary angiography [13]. Compared to the entire reference cohort (reference group 1 in Table III), TAVI patients had a substantially higher risk of CA, CAS, and severe
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TABLE I. Baseline Study Population Characteristics Total (n ¼ 171) Age, years (mean 6 SD, range) Male gender (n, %) Diabetes Mellitus (n, %) Dyslipidemia (n, %) Hypertension (n, %) Smoking history (n, %) Height (mean 6 SD) Weight (mean 6 SD) BMI (mean 6 SD; Kg/m2) CrCl (mean 6 SD; ml/min) PVD (n, %) Stroke (n, %) Systolic heart failure (n, %) Prior MI Prior CABG Prior PCI AF (any type) (n, %) EF % (mean 6 SD) STS score (mean 6 SD) Euroscore (mean 6 SD) Coronary angiography Normal or nonobstructive One vessel disease Two vessel disease Three vessel disease Left Main disease MCV valve size (n, %) 23 mm 26 mm 29 mm 31 mm ESX valve size (n, %) 23 mm 26 mm 29 mm Portico valve size (n, %) 25 mm Hospitalization days (mean 6 SD)
82 6 6, 61–95 81, 47% 65, 38% 141, 83% 150, 88% 64, 37% 163 6 9 72 6 14 27 6 5 63 6 21 8, 5% 18, 11% 26, 15% 32, 19% 35, 21% 79, 46% 51, 30% 56 6 7 4.4 6 3 18.0 6 13 70, 41% 36, 21% 24, 14% 41, 24% 10, 6% 6, 4% 53, 31% 39, 23% 1,
