ORIGINAL RESEARCH IN MEDICINE published: 15 April 2015 doi: 10.3389/fcvm.2015.00018
Coronary artery disease and symptomatic severe aortic valve stenosis: clinical outcomes after transcatheter aortic valve implantation Jennifer Mancio 1 *, Ricardo Fontes-Carvalho 1,2 , Marco Oliveira 1 , Daniel Caeiro 1 , Pedro Braga 1 , Nuno Bettencourt 1,2 and Vasco Gama Ribeiro 1 1 2
Department of Cardiology, Gaia Hospital Center, Vila Nova de Gaia, Portugal Cardiovascular R&D Unit, Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine of Porto University, Porto, Portugal
Edited by: Carlos Escobar, Hospital Universitario La Paz, Spain Reviewed by: Daryl Schwenke, University of Otago, New Zealand Christoph Liebetrau, Kerckhoff Heart and Thorax Center, Germany David Marti, Hospital Central de la Defensa and Universidad de Alcalá, Spain *Correspondence: Jennifer Mancio, Rua Conceição Fernandes, Vila Nova de Gaia, Portugal e-mail: [email protected]
Introduction: The impact of coronary artery disease (CAD) on outcomes after transcatheter aortic valve implantation (TAVI) has not been clarified. Furthermore, less is known about the indication and strategy of revascularization in these high risk patients. Aims: This study sought to determine the prevalence and prognostic impact of CAD in patients undergoingTAVI, and to assess the safety and feasibility of percutaneous coronary intervention (PCI) before TAVI. Methods: Patients with severe aortic stenosis (AS) undergoing TAVI were included into a prospective single center registry from 2007 to 2012. Clinical outcomes were compared between patients with and without CAD. In some patients with CAD, it was decided to perform elective PCI before TAVI after decision by the Heart team. The primary endpoints were 30-day and 2-year all-cause mortality. Results: A total of 91 consecutive patients with mean age of 79 ± 9 years (52% men) underwent TAVI with a median follow-up duration of 16 months (interquartile range of 27.6 months). CAD was present on 46 patients (51%). At 30-day, the incidences of death were similar between CAD and non-CAD patients (9 and 5%, p = 0.44), but at 2 years were 50% in CAD patients and 24% in non-CAD patients [crude hazard ratio with CAD, 2.2; 95% confidence interval (CI), 1.1–4.6; p = 0.04]. Adjusting for age, gender, left ventricular ejection fraction, and glomerular filtration rate, the hazard of death was 2.6-fold higher in patients with CAD (95% CI, 1.1–6.0; p = 0.03). Elective PCI before TAVI was performed in 13 patients (28% of CAD patients). There were no more adverse events in patients who underwent TAVI + PCI when compared with those who underwent isolated TAVI. Conclusion: In severe symptomatic AS who underwent TAVI, CAD is frequent and adversely impacts long-term outcomes, but not procedure outcomes. In selected patients, PCI before TAVI appears to be feasible and safe. Keywords: coronary disease, aortic valve stenosis, transcatheter aortic valve implantation, percutaneous coronary angioplasty intervention, prognosis
INTRODUCTION Coronary artery disease (CAD) affects 25–50% of patients with severe aortic stenosis (AS) who undergo surgical aortic valve replacement (SAVR). (1) Its presence negatively impacts the periprocedural and long-term outcomes after SAVR. However, improved long-term survival has been reported in patients with AS and CAD who underwent combined SAVR and CABG compared with those receiving isolated SAVR (2). Based on these findings, current guidelines recommend bypass surgery to all significant stenosis at the time of SAVR (3, 4). The prevalence and impact of CAD on outcomes after transcatheter aortic valve implantation (TAVI) have not been fully delineated. Published studies specifically addressing this issue are
www.frontiersin.org
sparse and controversial (5–8). Moreover, the only randomized clinical trial that compares SAVR with TAVI excluded patients with CAD requiring revascularization (9). Consequently, the original TAVI protocol precludes that significant CAD must be treated by percutaneous coronary intervention (PCI) before TAVI, and that CAD not treatable by PCI should be considered a formal contraindication for TAVI (4, 10). However, it is unknown if revascularization in the high-risk population referred to TAVI is associated with similar benefits to those observed in patient referred to SAVR. Furthermore, performing PCI in a patient with severe AS can be problematic; thus, the risks of PCI in the setting of AS are unknown (11). Since CABG is the primary mode of revascularization in patients with CAD and moderate to severe
April 2015 | Volume 2 | Article 18 | 1
Mancio et al.
AS, PCI has been limited to patients with AS who presented with acute coronary syndrome. Furthermore, the safety of TAVI has just been investigated isolated from concomitant revascularization procedures (12, 13). The aims of the present study were to determine the prevalence of CAD and its impact on procedural outcomes and long-term survival in patients undergoing TAVI, and to assess the safety and feasibility of PCI before TAVI.
MATERIALS AND METHODS PATIENT POPULATION
Consecutive patients with symptomatic AS undergoing TAVI at Centro Hospitalar de Vila Nova de Gaia were enrolled in a prospective registry from August 2007 to October 2012. The study complied with the declaration of Helsinki, and the registry was approved by the local ethics committee. All the patients provided written informed consent to participate in our registry with prospective follow-up assessment. Initial assessment included clinical evaluation by the Heart Team, transthoracic and transesophageal echocardiography, invasive coronary angiography, and computed tomography of the aorta, iliac, and common femoral arteries. In all patients, the logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE), EuroSCORE 2 (14), and the Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) (15) were calculated. Patients were excluded from the analysis if the procedure was considered unsuccessful according to criteria in the Valve Academic Research Consortium (VARC-I) guidelines (16). TAVI was performed using the Medtronic CoreValve system (Medtronic, Minneapolis, MN, USA) or the Edwards SAPIEN valve (Edwards Lifesciences, Irvine, CA, USA) by transfemoral, transapical, or transsubclavian approach according to the instructions for use and as previously described (9, 12). Devices and access site were selected by anatomical and technical features. In some patients, it was decided to perform elective PCI before TAVI either in a planned intervention prior to TAVI (staged PCI) or at the time of TAVI (concomitant PCI). In cases of concomitant PCI, patients first underwent PCI followed by TAVI in the same session. Revascularization strategy was based on the amount of myocardium at risk, which was estimated integrating the visual assessment of the coronary anatomy, the presence of wall motion alteration in the echocardiogram, and history of prior myocardial infarction. On the day before TAVI, patients undergoing isolated TAVI were medicated with 250 mg of aspirin and 300 mg of clopidogrel, and the patients undergoing concomitant PCI were medicated with 250 mg of acetylsalicylic acid and 600 mg of clopidogrel. Procedural anticoagulation was obtained with a heparin bolus of 70 IU/kg, aiming for an activated clotting time of 250–300 ms. ANGIOGRAPHIC ANALYSIS
For the purpose of this study, baseline coronary angiographies were analyzed by two experienced interventional cardiologists. CAD group included patients with at least one lesion on the epicardial coronary arteries with ≥50% diameter stenosis or patients who had been submitted to coronary revascularization by PCI or CABG before AS diagnosis.
Frontiers in Cardiovascular Medicine | General Cardiology
Transcatheter aortic valve implantation and coronary artery disease
STUDY END POINTS AND DEFINITIONS
Primary end points included 30-day and 2-year all-cause mortality. Prespecified secondary end points included mortality from cardiovascular causes, myocardial infarction, stroke, acute renal injury, vascular complications, bleeding, new onset atrial fibrillation, and pacemaker implantation. In a retrospective analysis of neurologic events, major stroke was defined by a score of at least 2 on the modified Rankin scale (which ranges from 0 to 6, with higher scores indicating greater disability). All events were adjudicated according to the VARC I definitions (16) by a clinical event committee consisting of invasive cardiologists and cardiac surgeons. Patients were followed during the index hospitalization and at 30 days, 6 months, 1 year, and yearly thereafter. STATISTICAL ANALYSIS
Patients were stratified into two groups according to the presence or absence of CAD. Baseline characteristics and clinical outcomes were compared between groups. Continuous variables were described using the mean ± SD if normally distributed or median and interquartile range (IQR) when non-normally distributed. Student’s t -test was used for the comparisons between continuous variables if normally distributed, and Mann–Whitney U in cases of non-normally distributed variables. Categorical variables were described using relative frequencies, and compared between CAD and non-CAD patients using the Chi-square test or Fisher exact test when appropriate. Clinical outcomes at 30 days and 2 years were expressed as counts or incidence rates computed according to Kaplan–Meier analysis. Hazard ratios were derived from MantelCox log-rank for all-cause mortality. Clinical outcomes at 30 days and 2 years were also compared between patients with and without CAD. A Cox multivariate regression analysis was performed to determine adjusted hazard ratio of death between groups. We estimated that a sample size of 91 patients (controls ratio of 0.49) allowed the detection of an hazard ratio difference of 0.5 for the primary end point with a type II error of 20% and a significance level of 5% (two-sample comparison of survivor functions logrank test by the Freedman method). To assess feasibility and safety of PCI before TAVI, the clinical outcomes at 30 days were compared between patients with CAD who underwent isolated TAVI and TAVI + PCI. A p-value
Coronary artery disease and symptomatic severe aortic valve stenosis: clinical outcomes after transcatheter aortic valve implantation Jennifer Mancio 1 *, Ricardo Fontes-Carvalho 1,2 , Marco Oliveira 1 , Daniel Caeiro 1 , Pedro Braga 1 , Nuno Bettencourt 1,2 and Vasco Gama Ribeiro 1 1 2
Department of Cardiology, Gaia Hospital Center, Vila Nova de Gaia, Portugal Cardiovascular R&D Unit, Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine of Porto University, Porto, Portugal
Edited by: Carlos Escobar, Hospital Universitario La Paz, Spain Reviewed by: Daryl Schwenke, University of Otago, New Zealand Christoph Liebetrau, Kerckhoff Heart and Thorax Center, Germany David Marti, Hospital Central de la Defensa and Universidad de Alcalá, Spain *Correspondence: Jennifer Mancio, Rua Conceição Fernandes, Vila Nova de Gaia, Portugal e-mail: [email protected]
Introduction: The impact of coronary artery disease (CAD) on outcomes after transcatheter aortic valve implantation (TAVI) has not been clarified. Furthermore, less is known about the indication and strategy of revascularization in these high risk patients. Aims: This study sought to determine the prevalence and prognostic impact of CAD in patients undergoingTAVI, and to assess the safety and feasibility of percutaneous coronary intervention (PCI) before TAVI. Methods: Patients with severe aortic stenosis (AS) undergoing TAVI were included into a prospective single center registry from 2007 to 2012. Clinical outcomes were compared between patients with and without CAD. In some patients with CAD, it was decided to perform elective PCI before TAVI after decision by the Heart team. The primary endpoints were 30-day and 2-year all-cause mortality. Results: A total of 91 consecutive patients with mean age of 79 ± 9 years (52% men) underwent TAVI with a median follow-up duration of 16 months (interquartile range of 27.6 months). CAD was present on 46 patients (51%). At 30-day, the incidences of death were similar between CAD and non-CAD patients (9 and 5%, p = 0.44), but at 2 years were 50% in CAD patients and 24% in non-CAD patients [crude hazard ratio with CAD, 2.2; 95% confidence interval (CI), 1.1–4.6; p = 0.04]. Adjusting for age, gender, left ventricular ejection fraction, and glomerular filtration rate, the hazard of death was 2.6-fold higher in patients with CAD (95% CI, 1.1–6.0; p = 0.03). Elective PCI before TAVI was performed in 13 patients (28% of CAD patients). There were no more adverse events in patients who underwent TAVI + PCI when compared with those who underwent isolated TAVI. Conclusion: In severe symptomatic AS who underwent TAVI, CAD is frequent and adversely impacts long-term outcomes, but not procedure outcomes. In selected patients, PCI before TAVI appears to be feasible and safe. Keywords: coronary disease, aortic valve stenosis, transcatheter aortic valve implantation, percutaneous coronary angioplasty intervention, prognosis
INTRODUCTION Coronary artery disease (CAD) affects 25–50% of patients with severe aortic stenosis (AS) who undergo surgical aortic valve replacement (SAVR). (1) Its presence negatively impacts the periprocedural and long-term outcomes after SAVR. However, improved long-term survival has been reported in patients with AS and CAD who underwent combined SAVR and CABG compared with those receiving isolated SAVR (2). Based on these findings, current guidelines recommend bypass surgery to all significant stenosis at the time of SAVR (3, 4). The prevalence and impact of CAD on outcomes after transcatheter aortic valve implantation (TAVI) have not been fully delineated. Published studies specifically addressing this issue are
www.frontiersin.org
sparse and controversial (5–8). Moreover, the only randomized clinical trial that compares SAVR with TAVI excluded patients with CAD requiring revascularization (9). Consequently, the original TAVI protocol precludes that significant CAD must be treated by percutaneous coronary intervention (PCI) before TAVI, and that CAD not treatable by PCI should be considered a formal contraindication for TAVI (4, 10). However, it is unknown if revascularization in the high-risk population referred to TAVI is associated with similar benefits to those observed in patient referred to SAVR. Furthermore, performing PCI in a patient with severe AS can be problematic; thus, the risks of PCI in the setting of AS are unknown (11). Since CABG is the primary mode of revascularization in patients with CAD and moderate to severe
April 2015 | Volume 2 | Article 18 | 1
Mancio et al.
AS, PCI has been limited to patients with AS who presented with acute coronary syndrome. Furthermore, the safety of TAVI has just been investigated isolated from concomitant revascularization procedures (12, 13). The aims of the present study were to determine the prevalence of CAD and its impact on procedural outcomes and long-term survival in patients undergoing TAVI, and to assess the safety and feasibility of PCI before TAVI.
MATERIALS AND METHODS PATIENT POPULATION
Consecutive patients with symptomatic AS undergoing TAVI at Centro Hospitalar de Vila Nova de Gaia were enrolled in a prospective registry from August 2007 to October 2012. The study complied with the declaration of Helsinki, and the registry was approved by the local ethics committee. All the patients provided written informed consent to participate in our registry with prospective follow-up assessment. Initial assessment included clinical evaluation by the Heart Team, transthoracic and transesophageal echocardiography, invasive coronary angiography, and computed tomography of the aorta, iliac, and common femoral arteries. In all patients, the logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE), EuroSCORE 2 (14), and the Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) (15) were calculated. Patients were excluded from the analysis if the procedure was considered unsuccessful according to criteria in the Valve Academic Research Consortium (VARC-I) guidelines (16). TAVI was performed using the Medtronic CoreValve system (Medtronic, Minneapolis, MN, USA) or the Edwards SAPIEN valve (Edwards Lifesciences, Irvine, CA, USA) by transfemoral, transapical, or transsubclavian approach according to the instructions for use and as previously described (9, 12). Devices and access site were selected by anatomical and technical features. In some patients, it was decided to perform elective PCI before TAVI either in a planned intervention prior to TAVI (staged PCI) or at the time of TAVI (concomitant PCI). In cases of concomitant PCI, patients first underwent PCI followed by TAVI in the same session. Revascularization strategy was based on the amount of myocardium at risk, which was estimated integrating the visual assessment of the coronary anatomy, the presence of wall motion alteration in the echocardiogram, and history of prior myocardial infarction. On the day before TAVI, patients undergoing isolated TAVI were medicated with 250 mg of aspirin and 300 mg of clopidogrel, and the patients undergoing concomitant PCI were medicated with 250 mg of acetylsalicylic acid and 600 mg of clopidogrel. Procedural anticoagulation was obtained with a heparin bolus of 70 IU/kg, aiming for an activated clotting time of 250–300 ms. ANGIOGRAPHIC ANALYSIS
For the purpose of this study, baseline coronary angiographies were analyzed by two experienced interventional cardiologists. CAD group included patients with at least one lesion on the epicardial coronary arteries with ≥50% diameter stenosis or patients who had been submitted to coronary revascularization by PCI or CABG before AS diagnosis.
Frontiers in Cardiovascular Medicine | General Cardiology
Transcatheter aortic valve implantation and coronary artery disease
STUDY END POINTS AND DEFINITIONS
Primary end points included 30-day and 2-year all-cause mortality. Prespecified secondary end points included mortality from cardiovascular causes, myocardial infarction, stroke, acute renal injury, vascular complications, bleeding, new onset atrial fibrillation, and pacemaker implantation. In a retrospective analysis of neurologic events, major stroke was defined by a score of at least 2 on the modified Rankin scale (which ranges from 0 to 6, with higher scores indicating greater disability). All events were adjudicated according to the VARC I definitions (16) by a clinical event committee consisting of invasive cardiologists and cardiac surgeons. Patients were followed during the index hospitalization and at 30 days, 6 months, 1 year, and yearly thereafter. STATISTICAL ANALYSIS
Patients were stratified into two groups according to the presence or absence of CAD. Baseline characteristics and clinical outcomes were compared between groups. Continuous variables were described using the mean ± SD if normally distributed or median and interquartile range (IQR) when non-normally distributed. Student’s t -test was used for the comparisons between continuous variables if normally distributed, and Mann–Whitney U in cases of non-normally distributed variables. Categorical variables were described using relative frequencies, and compared between CAD and non-CAD patients using the Chi-square test or Fisher exact test when appropriate. Clinical outcomes at 30 days and 2 years were expressed as counts or incidence rates computed according to Kaplan–Meier analysis. Hazard ratios were derived from MantelCox log-rank for all-cause mortality. Clinical outcomes at 30 days and 2 years were also compared between patients with and without CAD. A Cox multivariate regression analysis was performed to determine adjusted hazard ratio of death between groups. We estimated that a sample size of 91 patients (controls ratio of 0.49) allowed the detection of an hazard ratio difference of 0.5 for the primary end point with a type II error of 20% and a significance level of 5% (two-sample comparison of survivor functions logrank test by the Freedman method). To assess feasibility and safety of PCI before TAVI, the clinical outcomes at 30 days were compared between patients with CAD who underwent isolated TAVI and TAVI + PCI. A p-value
