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Analysis of length of hospital stay after Transfemoral Transcatheter Aortic Valve Implantation: Results from the FRANCE TAVI (FRench Transcatheter Aortic Valve Implantation) Registry
Archives of Cardiovascular Disease Supplements (2019) 11, 253—257
Available online at
ScienceDirect www.sciencedirect.com
Topic 22—Valvular heart disease, congenital cardiopathy—C Wednesday, April 3, 2019 037
Characteristics, prognosis of moderate aortic stenosis G. Delesalle ∗ , Y. Bohbot , C. Tribouilloy Department of cardiology, Amiens University hospital, Amiens, France ∗ Corresponding author. E-mail address: [email protected] (G. Delesalle) Introduction Moderate aortic stenosis (MAS) has not been extensively studied and characterized, as no published study has been specifically devoted to this condition. Objective We aimed to describe the characteristics of patients with MAS and to evaluate their long-term survival compared to that of the general population. Method This study included 508 patients (mean age 75 ± 11 years) with MAS (aortic valve area [AVA] between 1 and 1.5 cm2 , mean AVA 1.2 ± 0.15 cm2 ). Patients were mostly (86.4%) asymptomatic or minimally symptomatic, 78.3% had hypertension, 36.2% were diabetics and 48.3% had dyslipidemia. Survival of MAS patients was compared with the expected survival of age- and sex-matched individuals of the general population. Results During follow-up, 113 patients (22.2%) underwent aortic valve replacement (AVR) for severe aortic stenosis. The mean time between inclusion and surgery was 37 ± 22 months. During followup, 255 patients (50.2%) died. The 6-year survival of patients with MAS was lower than the expected survival (53 ± 2% vs 65%). In multivariate analysis, age (HR = 1.04 [1.02—1.05]; P < 0.001), prior atrial fibrillation (HR = 1.35 [1.05—1.73]; P = 0.019) and Charlson comorbidity index (HR = 1.11 [1.05—1.18]; P = 0.002) were associated with increased mortality, while AVR was associated with better survival (HR = 0.38[0.27—0.54]; P < 0.001). Conclusion The results of this study show that patients with MAS present many cardiovascular risk factors, a high rate of surgery and increased mortality compared to the general population, mainly related to comorbidities. Patients with MAS should therefore be managed for their cardiovascular risk factors and require close
1878-6480/
follow-up, especially when the AVA is close to 1 cm2 , as AVR is associated with better survival. Disclosure of interest The authors declare that they have no competing interest. https://doi.org/10.1016/j.acvdsp.2019.02.153 174
Analysis of length of hospital stay after Transfemoral Transcatheter Aortic Valve Implantation: Results from the FRANCE TAVI (FRench Transcatheter Aortic Valve Implantation) Registry G. Avinee 1,2,∗ , H. Eltchaninoff 1,2 , C. Tron 1 , N. Bettinger 1 , N. Bouhzam 1 , M. Gilard 3 , J.P. Verhoye 4 , R. Koning 5 , T. Lefevre 6 , E. Van Belle 7 , P. Leprince 8 , B. Iung 9 , H. Le Breton 10,11 , E. Durand 1,2 1 Department of Cardiology, Rouen University Hospital 2 Cardiologie, CHU de Rouen 3 Normandie Université, UNIROUEN, Inserm U1096, FHU Remod-VHF, Rouen 4 Department of Cardiology, Brest University Hospital, Brest 5 Department of Cardiac surgery, Rennes University Hospital, Rennes 6 Department of Cardiology, Clinique Saint-Hilaire, Rouen 7 Department of Cardiology, Institut Hospitalier Jacques-Cartier, Massy 8 Department of Cardiology, Lille University hospital, Lille 9 Department of Cardiac surgery, Pitié-Salpêtrière hospital 10 Department of Cardiology, Inserm U1148, Bichat Hospital, Paris 11 Department of Cardiology, Rennes University Hospital, Rennes, France ∗ Corresponding author. E-mail address: [email protected] (G. Avinee) Introduction Transcatheter aortic valve implantation (TAVI) is playing a growing role in the management of patients with symptomatic severe aortic stenosis. However, length of hospital stay (LOS) after transfemoral (TF) TAVI remains widely variable.
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Topic 22—Valvular heart disease, congenital cardiopathy—C
Objective We aimed to evaluate LOS after TF TAVI and the variability of LOS among French centers using data from the FRANCE TAVI registry. Methods TAVI was performed in 12,804 patients in 48 French centers between January 2013 and December 2015. LOS was evaluated in 5,857 (45.7%) patients treated via a TF approach and discharged directly at home. LOS was calculated from TAVI procedure (day 0) to discharge. The study population was divided into 2 groups based on tertile LOS values. Results The median LOS in the studied population was 7 (5—9) days and was extremely variable among centers. Patients in the lowest tertile (LOS < 6 days, n = 2,233) constituted the ‘‘Early Discharge’’ group, and patients with a length of stay > 6 days (n = 3,624) constituted the ‘‘Late Discharge group’’. Variables independently associated with late discharge were comorbidities (history of mitral valve prosthesis, respiratory failure, atrial fibrillation, and severe pulmonary hypertension), complications occurring during or after TAVI (need for a new pacemaker, tamponade, stroke, vascular complications and acute kidney injury), the use of self-expandable valve and general anesthesia with a significant center effect. In contrast, the history of previous pacemaker before TAVI was a protective factor. Finally, we did not observe any significant difference in the rate of death and re-admission in the early versus late discharge groups. Conclusion LOS remain high after TF TAVI in France and extremely variable. As expected, co-morbidities and complications were predictive factors of late discharge after TAVI. Furthermore, our results suggest that the use of self-expandable prosthesis and general anesthesia also contributes to late discharge. Disclosure of interest The authors declare that they have no competing interest.
blast marker ACTA2 was decreased. VIC fibroblastic phenotype was restored and calcification decreased when hVICs were co-cultured with healthy hVECs or incubated with ET-1 antagonist. Conclusion The present study suggests that ET-1 play a role in the pathogenesis of AS, and therefore, pharmacological ET-1 antagonists could be used to attenuate or stop VIC calcification. Disclosure of interest The authors declare that they have no competing interest.
https://doi.org/10.1016/j.acvdsp.2019.02.154 199
Implication of endothelin-1 in human aortic valve calcification B. Colleville 1,∗ , N. Perzo 1 , H. Eltchaninoff 1,2 , V. Richard 1,2 , E. Durand 1,2 1 Normandie University, Institute for Research and Innovation in Biomedicine, Inserm U1096, Endothelium, Valvulopathy and Heart Failure, FHU REMOD-VHF 2 University Hospital, Department of Cardiology, Rouen, France ∗ Corresponding author. E-mail address: [email protected] (B. Colleville) Introduction Aortic Stenosis (AS) is the most common acquired valvulopathy in the Western world. AS is characterized by the differenciation of valvular interstitial cells (VICs) into osteoblastic cells, leading to valvular calcification. The physiopathology of AS is not fully understood and there is, to date, no treatments to stop or slow the progression of AS. Objective The purpose of our study was to investigate the role of endothelin-1 (ET-1) on VICs calcification. Method Primary human valvular interstitial cells (hVICs) were first cultured in pro-osteogenic medium or incubated with ET1. hVICs were also co-cultured with human valvular endothelial cells (hVECs) obtained from patients with (pathological) or without (healthy) AS in TranswellTM inserts. hVICs calcification was quantified using o-cresolphthalein assay. Real-time quantitative PCR (qRT-PCR) and Western blot analysis were performed to determine the expression of ET-1 (EDN1), inflammation (IL1B, IL6) and bone markers (RUNX2, OPG, OPN). Immunochemistry was performed using ACTA2 antibody to evaluate the phenotype of VICs. Results hVICs showed an increase of calcification and a decrease of ACTA2 when cultured in pro-osteogenic medium or co-cultured with pathological hVECs. qRT-PCR revealed higher mRNA levels of EDN1, RUNX2, OPG, OPN, IL1B and IL6. At the same time, fibro-
https://doi.org/10.1016/j.acvdsp.2019.02.155 316
Functional characterization of PALMD risk locus in calcific aortic valve stenosis R. Mickael 1,∗ , M.C. Boulanger 1 , R. Devillers 1 , A. Chignon 1 , D. Argaud 1 , G. Mkannez 1 , Z. Li 1,2 , G. Rhéaume 1 , N. Gaudreault 2 , S. Thériault 3 , Y. Bossé 2 , P. Mathieu 1 1 Laboratory of Cardiovascular Pathobiology, Quebec Heart and Lung, Institute/Research Center, Department of Surgery, Laval University, Québec 2 Department of Molecular Medicine, Laval University, Québec 3 Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University, Québec, Canada ∗ Corresponding author. E-mail address: [email protected] (R. Mickael) Introduction Calcific aortic valve stenosis (CAVS) is the most common heart valve disorder. Genome and transcriptome-wide association studies identified risk variant rs6702619 at the PALMD locus as casually associated with CAVS and with lower PALMD expression. Objective To map and fine-grain molecular analyses to probe the regulation and function of PALMD. Methods Regulation of the PALMD risk locus and its impact on valve interstitial cells (VICs) were evaluated. Reporter assays, DNA-binding assays and CRISPR-mediated gene activation were performed to study the role of rs6702619 on the expression of PALMD. PALMD interactome was assessed by LC/MS/MS and functions of PALMD were investigated. Results Functional mapping prioritized rs6702619 as a causal noncoding variant. Analysis of chromatin interactions showed that the risk locus interacts with the promoter of PALMD. CRISPR activation at rs6702619 increased the expression of PALMD by 30%. The variant rs6702619 is located in a binding site for NFATC2, a transcription factor involved in valve embryology. The presence of the risk variant modifies DNA shape as shown by the analysis of atomic resolution structure. Reporter assays demonstrated a decrease in the response to NFATC2 by 5.8 fold with the risk allele. DNAprotein interaction ELISA revealed that the risk allele decreased the affinity for NFATC2. Actin was identified in PALMD interactome and in vitro data showed that PALMD is a novel regulator of actin polymerization. Downregulation of PALMD expression in VICs promoted a myofibroblastic program leading to actin polymerization in stress fibers and the expression of alpha-actin and collagen. Conclusions The risk variant rs6702619 is located in a binding site for NFATC2, modifies DNA shape and decreases enhancermediated expression of PALMD. PALMD downregulation in VICs results in actin polymerization, a myofibroblast-like phenotype and promotes fibrosis processes, a key feature in the pathogenesis of CAVS. Disclosure of interest The authors declare that they have no competing interest. https://doi.org/10.1016/j.acvdsp.2019.02.156
Available online at
ScienceDirect www.sciencedirect.com
Topic 22—Valvular heart disease, congenital cardiopathy—C Wednesday, April 3, 2019 037
Characteristics, prognosis of moderate aortic stenosis G. Delesalle ∗ , Y. Bohbot , C. Tribouilloy Department of cardiology, Amiens University hospital, Amiens, France ∗ Corresponding author. E-mail address: [email protected] (G. Delesalle) Introduction Moderate aortic stenosis (MAS) has not been extensively studied and characterized, as no published study has been specifically devoted to this condition. Objective We aimed to describe the characteristics of patients with MAS and to evaluate their long-term survival compared to that of the general population. Method This study included 508 patients (mean age 75 ± 11 years) with MAS (aortic valve area [AVA] between 1 and 1.5 cm2 , mean AVA 1.2 ± 0.15 cm2 ). Patients were mostly (86.4%) asymptomatic or minimally symptomatic, 78.3% had hypertension, 36.2% were diabetics and 48.3% had dyslipidemia. Survival of MAS patients was compared with the expected survival of age- and sex-matched individuals of the general population. Results During follow-up, 113 patients (22.2%) underwent aortic valve replacement (AVR) for severe aortic stenosis. The mean time between inclusion and surgery was 37 ± 22 months. During followup, 255 patients (50.2%) died. The 6-year survival of patients with MAS was lower than the expected survival (53 ± 2% vs 65%). In multivariate analysis, age (HR = 1.04 [1.02—1.05]; P < 0.001), prior atrial fibrillation (HR = 1.35 [1.05—1.73]; P = 0.019) and Charlson comorbidity index (HR = 1.11 [1.05—1.18]; P = 0.002) were associated with increased mortality, while AVR was associated with better survival (HR = 0.38[0.27—0.54]; P < 0.001). Conclusion The results of this study show that patients with MAS present many cardiovascular risk factors, a high rate of surgery and increased mortality compared to the general population, mainly related to comorbidities. Patients with MAS should therefore be managed for their cardiovascular risk factors and require close
1878-6480/
follow-up, especially when the AVA is close to 1 cm2 , as AVR is associated with better survival. Disclosure of interest The authors declare that they have no competing interest. https://doi.org/10.1016/j.acvdsp.2019.02.153 174
Analysis of length of hospital stay after Transfemoral Transcatheter Aortic Valve Implantation: Results from the FRANCE TAVI (FRench Transcatheter Aortic Valve Implantation) Registry G. Avinee 1,2,∗ , H. Eltchaninoff 1,2 , C. Tron 1 , N. Bettinger 1 , N. Bouhzam 1 , M. Gilard 3 , J.P. Verhoye 4 , R. Koning 5 , T. Lefevre 6 , E. Van Belle 7 , P. Leprince 8 , B. Iung 9 , H. Le Breton 10,11 , E. Durand 1,2 1 Department of Cardiology, Rouen University Hospital 2 Cardiologie, CHU de Rouen 3 Normandie Université, UNIROUEN, Inserm U1096, FHU Remod-VHF, Rouen 4 Department of Cardiology, Brest University Hospital, Brest 5 Department of Cardiac surgery, Rennes University Hospital, Rennes 6 Department of Cardiology, Clinique Saint-Hilaire, Rouen 7 Department of Cardiology, Institut Hospitalier Jacques-Cartier, Massy 8 Department of Cardiology, Lille University hospital, Lille 9 Department of Cardiac surgery, Pitié-Salpêtrière hospital 10 Department of Cardiology, Inserm U1148, Bichat Hospital, Paris 11 Department of Cardiology, Rennes University Hospital, Rennes, France ∗ Corresponding author. E-mail address: [email protected] (G. Avinee) Introduction Transcatheter aortic valve implantation (TAVI) is playing a growing role in the management of patients with symptomatic severe aortic stenosis. However, length of hospital stay (LOS) after transfemoral (TF) TAVI remains widely variable.
254
Topic 22—Valvular heart disease, congenital cardiopathy—C
Objective We aimed to evaluate LOS after TF TAVI and the variability of LOS among French centers using data from the FRANCE TAVI registry. Methods TAVI was performed in 12,804 patients in 48 French centers between January 2013 and December 2015. LOS was evaluated in 5,857 (45.7%) patients treated via a TF approach and discharged directly at home. LOS was calculated from TAVI procedure (day 0) to discharge. The study population was divided into 2 groups based on tertile LOS values. Results The median LOS in the studied population was 7 (5—9) days and was extremely variable among centers. Patients in the lowest tertile (LOS < 6 days, n = 2,233) constituted the ‘‘Early Discharge’’ group, and patients with a length of stay > 6 days (n = 3,624) constituted the ‘‘Late Discharge group’’. Variables independently associated with late discharge were comorbidities (history of mitral valve prosthesis, respiratory failure, atrial fibrillation, and severe pulmonary hypertension), complications occurring during or after TAVI (need for a new pacemaker, tamponade, stroke, vascular complications and acute kidney injury), the use of self-expandable valve and general anesthesia with a significant center effect. In contrast, the history of previous pacemaker before TAVI was a protective factor. Finally, we did not observe any significant difference in the rate of death and re-admission in the early versus late discharge groups. Conclusion LOS remain high after TF TAVI in France and extremely variable. As expected, co-morbidities and complications were predictive factors of late discharge after TAVI. Furthermore, our results suggest that the use of self-expandable prosthesis and general anesthesia also contributes to late discharge. Disclosure of interest The authors declare that they have no competing interest.
blast marker ACTA2 was decreased. VIC fibroblastic phenotype was restored and calcification decreased when hVICs were co-cultured with healthy hVECs or incubated with ET-1 antagonist. Conclusion The present study suggests that ET-1 play a role in the pathogenesis of AS, and therefore, pharmacological ET-1 antagonists could be used to attenuate or stop VIC calcification. Disclosure of interest The authors declare that they have no competing interest.
https://doi.org/10.1016/j.acvdsp.2019.02.154 199
Implication of endothelin-1 in human aortic valve calcification B. Colleville 1,∗ , N. Perzo 1 , H. Eltchaninoff 1,2 , V. Richard 1,2 , E. Durand 1,2 1 Normandie University, Institute for Research and Innovation in Biomedicine, Inserm U1096, Endothelium, Valvulopathy and Heart Failure, FHU REMOD-VHF 2 University Hospital, Department of Cardiology, Rouen, France ∗ Corresponding author. E-mail address: [email protected] (B. Colleville) Introduction Aortic Stenosis (AS) is the most common acquired valvulopathy in the Western world. AS is characterized by the differenciation of valvular interstitial cells (VICs) into osteoblastic cells, leading to valvular calcification. The physiopathology of AS is not fully understood and there is, to date, no treatments to stop or slow the progression of AS. Objective The purpose of our study was to investigate the role of endothelin-1 (ET-1) on VICs calcification. Method Primary human valvular interstitial cells (hVICs) were first cultured in pro-osteogenic medium or incubated with ET1. hVICs were also co-cultured with human valvular endothelial cells (hVECs) obtained from patients with (pathological) or without (healthy) AS in TranswellTM inserts. hVICs calcification was quantified using o-cresolphthalein assay. Real-time quantitative PCR (qRT-PCR) and Western blot analysis were performed to determine the expression of ET-1 (EDN1), inflammation (IL1B, IL6) and bone markers (RUNX2, OPG, OPN). Immunochemistry was performed using ACTA2 antibody to evaluate the phenotype of VICs. Results hVICs showed an increase of calcification and a decrease of ACTA2 when cultured in pro-osteogenic medium or co-cultured with pathological hVECs. qRT-PCR revealed higher mRNA levels of EDN1, RUNX2, OPG, OPN, IL1B and IL6. At the same time, fibro-
https://doi.org/10.1016/j.acvdsp.2019.02.155 316
Functional characterization of PALMD risk locus in calcific aortic valve stenosis R. Mickael 1,∗ , M.C. Boulanger 1 , R. Devillers 1 , A. Chignon 1 , D. Argaud 1 , G. Mkannez 1 , Z. Li 1,2 , G. Rhéaume 1 , N. Gaudreault 2 , S. Thériault 3 , Y. Bossé 2 , P. Mathieu 1 1 Laboratory of Cardiovascular Pathobiology, Quebec Heart and Lung, Institute/Research Center, Department of Surgery, Laval University, Québec 2 Department of Molecular Medicine, Laval University, Québec 3 Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University, Québec, Canada ∗ Corresponding author. E-mail address: [email protected] (R. Mickael) Introduction Calcific aortic valve stenosis (CAVS) is the most common heart valve disorder. Genome and transcriptome-wide association studies identified risk variant rs6702619 at the PALMD locus as casually associated with CAVS and with lower PALMD expression. Objective To map and fine-grain molecular analyses to probe the regulation and function of PALMD. Methods Regulation of the PALMD risk locus and its impact on valve interstitial cells (VICs) were evaluated. Reporter assays, DNA-binding assays and CRISPR-mediated gene activation were performed to study the role of rs6702619 on the expression of PALMD. PALMD interactome was assessed by LC/MS/MS and functions of PALMD were investigated. Results Functional mapping prioritized rs6702619 as a causal noncoding variant. Analysis of chromatin interactions showed that the risk locus interacts with the promoter of PALMD. CRISPR activation at rs6702619 increased the expression of PALMD by 30%. The variant rs6702619 is located in a binding site for NFATC2, a transcription factor involved in valve embryology. The presence of the risk variant modifies DNA shape as shown by the analysis of atomic resolution structure. Reporter assays demonstrated a decrease in the response to NFATC2 by 5.8 fold with the risk allele. DNAprotein interaction ELISA revealed that the risk allele decreased the affinity for NFATC2. Actin was identified in PALMD interactome and in vitro data showed that PALMD is a novel regulator of actin polymerization. Downregulation of PALMD expression in VICs promoted a myofibroblastic program leading to actin polymerization in stress fibers and the expression of alpha-actin and collagen. Conclusions The risk variant rs6702619 is located in a binding site for NFATC2, modifies DNA shape and decreases enhancermediated expression of PALMD. PALMD downregulation in VICs results in actin polymerization, a myofibroblast-like phenotype and promotes fibrosis processes, a key feature in the pathogenesis of CAVS. Disclosure of interest The authors declare that they have no competing interest. https://doi.org/10.1016/j.acvdsp.2019.02.156