Publications by authors named "Thomas Cuisset"

179 Publications

Rapid deployment versus trans-catheter aortic valve replacement in intermediate-risk patients: A propensity score analysis.

J Card Surg 2021 Mar 9. Epub 2021 Mar 9.

Department of Cardiac Surgery, La Timone Hospital, Marseille, France.

Background: There are insufficient studies comparing rapid deployment aortic valve replacement (RDAVR) and trans-aortic valve replacement (TAVR) in intermediate-risk patients with severe aortic stenosis (AS).

Aims: We compared 2-year outcomes between RDAVR with INTUITY and TAVR with SAPIEN 3 in intermediate-risk patients with AS.

Methods: Inclusion criteria were patients with severe AS at a EuroSCORE II ≥ 4%, who received RDAVR or TAVR implantation and clinical evaluation by the Heart Team. Regression adjustment for the propensity score was used to compare RDAVR and TAVR. Primary outcome was the composite criterion of death, disabling stroke, or rehospitalization.

Secondary Outcomes: major bleeding complications postoperation, paravalvular regurgitation ≥ 2, patient-prosthesis mismatch, and pacemaker implantation.

Results: A total of 152 patients were included from 2012 to 2018: 48 in the RDAVR group and 104 in the TAVR group. The mean age was 82.7 ± 6.0,51.3% patients were female, the mean EuroSCORE II was 6.03 ± 1.6%, mean baseline LVEF was 56 ± 13%, mean indexed effective orifice area was 0.41 ± 0.1 cm/m , and the mean gradient was 51.7 ± 14.7 mmHg. RDAVR patients were younger (79.5 ± 6 years vs. 82.6 ± 6 years; p = .01), and at higher risk (EuroSCORE II, 6.61 ± 1.8% vs. 5.63 ± 1.5%; p = .005), Twenty-two patients (45.99%) in the RDAVR group and 32 (66.67%) in the TAVR group met the composite criterion. Through the 1:1 propensity score matching analysis, there was a significant difference between the groups, favoring RDAVR (HR = 0.58 [95% CI: 0.34-1.00]; p = .04). No differences were observed in terms of patient-prosthesis mismatch (0.83 [0.35-1.94]; p = .67), major bleeding events (1.33 [0.47-3.93]; p = .59), paravalvular regurgitation ≥ 2 (0.33[0-6.28]; p = .46), or pacemaker implantation (0.84 [0.25-2.84]; p = .77) CONCLUSION: RDAVR was associated with better 2-year outcomes than TAVR in intermediate-risk patients with severe symptomatic AS.
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http://dx.doi.org/10.1111/jocs.15483DOI Listing
March 2021

Prosthesis-patient mismatch is an independent predictor of congestive heart failure after transcatheter aortic valve replacement.

Arch Cardiovasc Dis 2021 Jan 25. Epub 2021 Jan 25.

Department of Cardiac Surgery, La Timone Hospital, 264, rue Saint-Pierre, 13005 Marseille, France.

Background: Little is known about the effect of prosthesis-patient mismatch (PPM) on outcomes after transcatheter aortic valve replacement. We reported previously an increased risk of PPM with the SAPIEN 3 transcatheter heart valve (S3-THV).

Aims: To investigate the association of PPM with 1-year outcomes in patients with severe aortic stenosis (AS) implanted with S3-THV.

Methods: Moderate PPM was defined by an indexed effective orifice area (iEOA)≤0.85cm/m, and severe PPM by an iEOA<0.65cm/m. Inclusion criteria were severe symptomatic AS and implantation with S3-THV. The primary endpoint was hospitalization for congestive heart failure (CHF) at 1 year; the secondary endpoint was all-cause mortality.

Results: A total of 208 consecutive patients were included between 2016 and 2018. Male sex was prevalent (53.8%), mean age was 81.9±6.2 years, mean EuroSCORE II was 4.35±3.37, mean LVEF was 57.9±13%. Moderate and severe PPM were observed in 69 (33.2%) and 10 (4.8%) patients. Patients with PPM were younger (80.4±7 vs 82.8±5.41 years; P=0.006), had a larger BSA (1.84±0.19 vs 1.77±0.19 m; P=0.01), a lower iEOA (0.73±0.08 vs 1.11±0.22 cm/m; P<0.001) and a higher mean gradient (14±4.6 vs 11.9±3.9mmHg; P<0.001). CHF occurred in 16.5% vs 7% (P=0.03). By multivariable analysis, PPM was independently associated with CHF (hazard ratio [HR] 3.17, 95% confidence interval [CI] 1.17 to 8.55; P=0.032), especially in patients with mitral regurgitation≥2/4 (HR>100, 95%CI>100 to>1000; P<0.01). PPM did not correlate with all-cause mortality (HR 0.90, 95%CI 0.22 to 3.03; P=0.86).

Conclusions: PPM after S3-THV implantation is strongly associated with CHF at 1 year, but is not correlated with overall mortality.
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http://dx.doi.org/10.1016/j.acvd.2020.11.005DOI Listing
January 2021

On-Ticagrelor Platelet Reactivity and Clinical Outcome in Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndrome.

Thromb Haemost 2020 Dec 1. Epub 2020 Dec 1.

Intensive care Unit, Department of Cardiology, Assistance publique des hopitaux de Marseille, Hôpital Nord, Aix Marseille University, Mediterranean Association for Research and Studies in Cardiology (MARS Cardio), Marseille, France.

Background:  A strong association between on-thienopyridine platelet reactivity (PR) and the risk of both thrombotic and bleeding events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) has been demonstrated. However, no study has analyzed the relationship between on-ticagrelor PR and clinical outcome in this clinical setting.

Objectives:  We aimed to investigate the relationship between on-ticagrelor PR, assessed by the vasodilator-stimulated phosphoprotein (VASP) index, and clinical outcome in patients with ACS undergoing PCI.

Methods:  We performed a prospective, multicenter, observational study of patients undergoing PCI for ACS. PR was measured using the VASP index following ticagrelor loading dose. The primary study endpoint was the rate of Bleeding Academic Research Consortium (BARC) type ≥2 at 1 year. The key secondary endpoint was the rate of major adverse cardiovascular events (MACE) defined as the composite of cardiovascular death, myocardial infarction, stroke, and urgent revascularization.

Results:  We included 570 ACS patients, among whom 33.9% had ST-elevation myocardial infarction. BARC type ≥2 bleeding occurred in 10.9% and MACE in 13.8%. PR was not associated with BARC ≥2 or with MACE ( = 0.12 and  = 0.56, respectively). No relationship between PR and outcomes was observed, neither when PR was analyzed quantitatively nor when it was analyzed qualitatively (low on-treatment PR [LTPR] vs. no LTPR).

Conclusion:  On-ticagrelor PR measured by the VASP was not associated with bleeding or thrombotic events in ACS patients undergoing PCI. PR measured by the VASP should not be used as a surrogate endpoint in studies on ticagrelor.
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http://dx.doi.org/10.1055/a-1326-5110DOI Listing
December 2020

Rotational atherectomy through a coronary artery bypass graft after transcatheter aortic valve implantation: a case report.

Eur Heart J Case Rep 2020 Oct 23;4(5):1-5. Epub 2020 Sep 23.

Département de Cardiologie, CHU Timone, Marseille F-13385, France.

Background : Aortic stenosis (AS) in the elderly is frequently associated with complex coronary artery disease. Rotational atherectomy (RA) in this clinical setting is challenging because coronary slow flow could lead to haemodynamic instability aggravated by the severe AS.

Case Summary : We present the case of an 83-year-old woman with symptomatic severe AS, mildly decreased left ventricular ejection fraction and history of coronary artery bypass grafting with right internal mammary artery (RIMA) to the right coronary artery (RCA) and left internal mammary artery to the left anterior descending artery and further percutaneous coronary intervention (PCI) to the circumflex. First, we performed a transcatheter aortic valve implantation (TAVI) to treat the severe AS. Because of persistent symptoms despite good result, we then performed RA of the native RCA through the RIMA with a Guidezilla guide extension catheter.

Discussion : A two-staged procedure of TAVI and PCI with RA of the RCA via RIMA was successfully performed. We decided to perform the PCI after the TAVI to allow a better haemodynamic tolerance of the complex coronary intervention. This procedure needs caution as the conduit is fragile and could be easily damaged during the RA. No data are available about feasibility and safety of RA through a native graft, but this could be a first step to consider it.
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http://dx.doi.org/10.1093/ehjcr/ytaa298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649512PMC
October 2020

Trial Design Principles for Patients at High Bleeding Risk Undergoing PCI: JACC Scientific Expert Panel.

J Am Coll Cardiol 2020 09;76(12):1468-1483

Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: https://twitter.com/Drroxmehran.

Investigating the balance of risk for thrombotic and bleeding events after percutaneous coronary intervention (PCI) is especially relevant for patients at high bleeding risk (HBR). The Academic Research Consortium for HBR recently proposed a consensus definition in an effort to standardize the patient population included in HBR trials. The aim of this consensus-based document, the second initiative from the Academic Research Consortium for HBR, is to propose recommendations to guide the design of clinical trials of devices and drugs in HBR patients undergoing PCI. The authors discuss the designs of trials in HBR patients undergoing PCI and various aspects of trial design specific to HBR patients, including target populations, intervention and control groups, primary and secondary outcomes, and timing of endpoint reporting.
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http://dx.doi.org/10.1016/j.jacc.2020.06.085DOI Listing
September 2020

Antithrombotic Therapy after Percutaneous Coronary Intervention of Bifurcation Lesions.

EuroIntervention 2020 Sep 15. Epub 2020 Sep 15.

Institute of Cardiology, University "G. d'Annuzio" of Chieti-Pescara, Italy.

Coronary bifurcations exhibit localized turbulent flow and enhanced propensity for platelet deposition, plaque rupture, and atherothrombosis. Percutaneous coronary intervention (PCI) of bifurcation lesions is associated with an increased risk of thrombotic events. Such risk is modulated by anatomical complexity, intraprocedural factors and pharmacological therapy. There is no consensus on the appropriate PCI strategy or the optimal regimen and duration of antithrombotic treatment in order to decrease the risk of ischemic and bleeding complications in the setting of coronary bifurcation. A uniform therapeutic approach meets a clinical need. The present initiative, promoted by the European Bifurcation Club (EBC), involves opinion leaders from Europe, America, and Asia with the aim to analyze the currently available evidence. Although mainly derived from sub-studies of large trials or small studies, or from authors' opinions, an algorithm for the optimal management of patients undergoing bifurcation PCI, developed on the basis of clinical presentation, bleeding risk, and intraprocedural strategy is here proposed.
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http://dx.doi.org/10.4244/EIJ-D-20-00885DOI Listing
September 2020

Re-intervention for failed surgical aortic bioprosthesis: Remaining questions on long term outcomes and selection of patients.

Int J Cardiol 2021 Jan 16;323:242. Epub 2020 Sep 16.

Département de Cardiologie, CHU Timone, Marseille, France; Aix Marseille Univ., Inserm, Inra, C2VN, Marseille, France; Aix-Marseille Université, Faculté de Médecine, Marseille, France. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2020.09.006DOI Listing
January 2021

Two-year outcomes after percutaneous coronary intervention with drug-eluting stents or bare-metal stents in elderly patients with coronary artery disease.

Catheter Cardiovasc Interv 2020 Aug 6. Epub 2020 Aug 6.

Cardiology Department Hôpital Cochin, Assistance Publique-Hôpitaux de Paris and, Université de Paris, Paris, France.

Objectives: Report the results at 2 years of the patients included in the SENIOR trial.

Background: Patients above 75 years of age represent a fast-growing population in the cathlab. In the SENIOR trial, patients treated by percutaneous coronary intervention (PCI) with drug eluting stent (DES) and a short duration of P2Y12 inhibitor (1 and 6 months for stable and unstable coronary syndromes, respectively) compared with bare metal stents (BMS) was associated with a 29% reduction in the rate of all-cause mortality, myocardial infarction (MI), stroke, and ischaemia-driven target lesion revascularization (ID-TLR) at 1 year. The results at 2 years are reported here.

Methods And Results: We randomly assigned 1,200 patients (596[50%] to the DES group and 604[50%] to the BMS group). At 2 years, the composite endpoint of all-cause mortality, MI, stroke and ID-TLR had occurred in 116 (20%) patients in the DES group and 131 (22%) patients in the BMS group (RR 0.90 [95%CI 0.72-1.13], p = .37). IDTLR occurred in 14 (2%) patients in the DES group and 41 (7%) patients in the BMS group (RR 0.35 [95%CI 0.16-0.60], p = .0002). Major bleedings (BARC 3-5) occurred in 27(5%) patients in both groups (RR 1.00, [95%CI 0.58-1.75], p = .99). Stent thrombosis rates were low and similar between DES and BMS (0.8 vs 1.3%, (RR 0.52 [95%CI 0.01-1.95], p = .27).

Conclusion: Among elderly PCI patients, a strategy combining a DES together with a short duration of DAPT is associated with a reduction in revascularization up to 2 years compared with BMS with very few late events and without any increased in bleeding complications or stent thrombosis.
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http://dx.doi.org/10.1002/ccd.29159DOI Listing
August 2020

Transcatheter Valve-in-Valve Aortic Valve Replacement as an Alternative to Surgical Re-Replacement.

J Am Coll Cardiol 2020 08;76(5):489-499

Service de Cardiologie, Centre Hospitalier Trousseau, Tours, France.

Background: Valve-in-valve (VIV) transcatheter aortic valve replacement (TAVR) and redo surgical aortic valve replacement (SAVR) represent the 2 treatments for aortic bioprosthesis failure. Clinical comparison of both therapies remains limited by the number of patients analyzed.

Objectives: The purpose of this study was to analyze the outcomes of VIV TAVR versus redo SAVR at a nationwide level in France.

Methods: Based on the French administrative hospital-discharge database, the study collected information for patients treated for aortic bioprosthesis failure with isolated VIV TAVR or redo SAVR between 2010 and 2019. Propensity score matching was used for the analysis of outcomes.

Results: A total of 4,327 patients were found in the database. After matching on baseline characteristics, 717 patients were analyzed in each arm. At 30 days, VIV TAVR was associated with lower rates of the composite of all-cause mortality, all-cause stroke, myocardial infarction, and major or life-threatening bleeding (odds ratio: 0.62; 95% confidence interval: 0.44 to 0.88; p = 0.03). During follow-up (median 516 days), the combined endpoint of cardiovascular death, all-cause stroke, myocardial infarction, or rehospitalization for heart failure was not different between the 2 groups (odds ratio: 1.18; 95% confidence interval: 0.99 to 1.41; p = 0.26). Rehospitalization for heart failure and pacemaker implantation were more frequently reported in the VIV TAVR group. A time-dependent interaction between all-cause and cardiovascular mortality following VIV TAVR was reported (p-interaction <0.05).

Conclusions: VIV TAVR was observed to be associated with better short-term outcomes than redo SAVR. Major cardiovascular outcomes were not different between the 2 treatments during long-term follow-up.
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http://dx.doi.org/10.1016/j.jacc.2020.06.010DOI Listing
August 2020

Homocysteine concentration and adenosine A receptor production by peripheral blood mononuclear cells in coronary artery disease patients.

J Cell Mol Med 2020 08 29;24(16):8942-8949. Epub 2020 Jun 29.

C2VN, INSERM, INRA, Aix Marseille University, Marseille, France.

Hyperhomocysteinemia is associated with coronary artery disease (CAD). The mechanistic aspects of this relationship are unclear. In CAD patients, homocysteine (HCy) concentration correlates with plasma level of adenosine that controls the coronary circulation via the activation of adenosine A receptors (A R). We addressed in CAD patients the relationship between HCy and A R production, and in cellulo the effect of HCy on A R function. 46 patients with CAD and 20 control healthy subjects were included. We evaluated A R production by peripheral blood mononuclear cells using Western blotting. We studied in cellulo (CEM human T cells) the effect of HCy on A R production as well as on basal and stimulated cAMP production following A R activation by an agonist-like monoclonal antibody. HCy concentration was higher in CAD patients vs controls (median, range: 16.6 [7-45] vs 8 [5-12] µM, P < 0.001). A R production was lower in patients vs controls (1.1[0.62-1.6] vs 1.53[0.7-1.9] arbitrary units, P < 0.001). We observed a negative correlation between HCy concentration and A R production (r = -0.43; P < 0.0001), with decreased A R production above 25 µM HCy. In cellulo, HCy inhibited A R production, as well as basal and stimulated cAMP production. In conclusion, HCy is negatively associated with A R production in CAD patients, as well as with A R and cAMP production in cellulo. The decrease in A R production and function, which is known to hamper coronary blood flow and promote inflammation, may support CAD pathogenesis.
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http://dx.doi.org/10.1111/jcmm.15527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417719PMC
August 2020

Valve-in-valve transcatheter aortic valve implantation after failed surgically implanted aortic bioprosthesis versus native transcatheter aortic valve implantation for aortic stenosis: Data from a nationwide analysis.

Arch Cardiovasc Dis 2021 Jan 10;114(1):41-50. Epub 2020 Jun 10.

Service de cardiologie, CHU Trousseau, 37044 Tours, France; EA7505, université de Tours, 37044 Tours, France.

Background: Valve-in-valve transcatheter aortic valve implantation (TAVI) has emerged as a treatment for aortic bioprosthesis failure in case of prohibitive risk for redo surgery. However, clinical evaluation of valve-in-valve TAVI remains limited by the number of patients analysed.

Aim: To evaluate outcomes of valve-in-valve TAVI compared with native aortic valve TAVI at a nationwide level in France.

Methods: Based on the French administrative hospital discharge database, the study collected information for all consecutive patients treated with TAVI for aortic stenosis or with isolated valve-in-valve TAVI for aortic bioprosthesis failure between 2010 and 2019. Propensity score matching was used for the analysis of outcomes.

Results: A total of 44,218 patients were found in the database. After matching on baseline characteristics, 2749 patients were analysed in each arm. At 30 days, no significant differences were observed regarding the occurrence of major clinical events (composite of cardiovascular mortality, all-cause stroke, myocardial infarction, major or life-threatening bleeding and conversion to open heart surgery) (odds ratio [OR] 0.83, 95% confidence interval [CI] 0.68-1.01; P=0.32). During follow-up (mean 516 days), the combined endpoint of cardiovascular death, all-cause stroke or rehospitalization for heart failure was not different between the valve-in-valve TAVI and native TAVI groups (RR 1.03, 95% CI 0.94-1.13; P=1.00).

Conclusion: We observed that valve-in-valve TAVI was associated with good short- and long-term outcomes. No significant differences were observed compared with native valve TAVI regarding clinical follow-up.
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http://dx.doi.org/10.1016/j.acvd.2020.04.005DOI Listing
January 2021

Contribution of exome sequencing to the identification of genes involved in the response to clopidogrel in cardiovascular patients.

J Thromb Haemost 2020 06 20;18(6):1425-1434. Epub 2020 Mar 20.

Geneva Platelet Group, Faculty of Medicine, University of Geneva, Geneva, Switzerland.

Background: On-clopidogrel platelet reactivity (PR) is associated with the risk of thrombotic or bleeding event in selected populations of high-risk patients. PR is a highly heritable phenotype and a few variants of cytochrome genes, essentially CYP2C19, are associated with PR but only explain 5% to 12% of the variability.

Objective: The aim of this study is to delineate genetic determinants of on-clopidogrel PR using high-throughput sequencing.

Methods: We performed a whole exome sequencing of 96 low- and matched high-PR patients in a discovery cohort. Exomes from genes with variants significantly associated with PR were sequenced in 96 low- and matched high-PR patients from an independent replication cohort.

Results: We identified 585 variants in 417 genes with an adjusted P value < .05. In the replication cohort, all top variants including CYP2C8, CYP2C18, and CYP2C19 from the discovery population were found again. An original network analysis identified several candidate genes of potential interest such as a regulator of PI3K, a key actor in the downstream signaling pathway of the P2Y receptor.

Conclusion: This study emphasizes the role of CYP-related genes as major regulators of clopidogrel response, including the poorly investigated CYP2C8 and CYP2C18.
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http://dx.doi.org/10.1111/jth.14776DOI Listing
June 2020

Usefulness of Routine Fractional Flow Reserve for Clinical Management of Coronary Artery Disease in Patients With Diabetes.

JAMA Cardiol 2020 03;5(3):272-281

Serviço de Cardiologia, Hospital de Santa Cruz-Centro Hospitalar de Lisboa Ocidental, Carnaxide, Portugal.

Importance: Approximately one-third of patients considered for coronary revascularization have diabetes, which is a major determinant of clinical outcomes, often influencing the choice of the revascularization strategy. The usefulness of fractional flow reserve (FFR) to guide treatment in this population is understudied and has been questioned.

Objective: To evaluate the usefulness and rate of major adverse cardiovascular events (MACE) of integrating FFR in management decisions for patients with diabetes who undergo coronary angiography.

Design, Setting, And Participants: This cross-sectional study used data from the PRIME-FFR study derived from the merger of the POST-IT study (Portuguese Study on the Evaluation of FFR-Guided Treatment of Coronary Disease [March 2012-November 2013]) and R3F study (French Study of FFR Integrated Multicenter Registries Implementation of FFR in Routine Practice [October 2008-June 2010]), 2 prospective multicenter registries that shared a common design. A population of all-comers for whom angiography disclosed ambiguous lesions was analyzed for rates, patterns, and outcomes associated with management reclassification, including revascularization deferral, in patients with vs without diabetes. Data analysis was performed from June to August 2018.

Main Outcomes And Measures: Death from any cause, myocardial infarction, or unplanned revascularization (MACE) at 1 year.

Results: Among 1983 patients (1503 [77%] male; mean [SD] age, 65 [10] years), 701 had diabetes, and FFR was performed for 1.4 lesions per patient (58.2% of lesions in the left anterior descending artery; mean [SD] stenosis, 56% [11%]; mean [SD] FFR, 0.81 [0.01]). Reclassification by FFR was high and similar in patients with and without diabetes (41.2% vs 37.5%, P = .13), but reclassification from medical treatment to revascularization was more frequent in the former (142 of 342 [41.5%] vs 230 of 730 [31.5%], P = .001). There was no statistical difference between the 1-year rates of MACE in reclassified (9.7%) and nonreclassified patients (12.0%) (P = .37). Among patients with diabetes, FFR-based deferral identified patients with a lower risk of MACE at 12 months (25 of 296 [8.4%]) compared with those undergoing revascularization (47 of 257 [13.1%]) (P = .04), and the rate was of the same magnitude of the observed rate among deferred patients without diabetes (7.9%, P = .87). Status of insulin treatment had no association with outcomes. Patients (6.6% of the population) in whom FFR was disregarded had the highest MACE rates regardless of diabetes status.

Conclusions And Relevance: Routine integration of FFR for the management of coronary artery disease in patients with diabetes may be associated with a high rate of treatment reclassification. Management strategies guided by FFR, including revascularization deferral, may be useful for patients with diabetes.
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http://dx.doi.org/10.1001/jamacardio.2019.5097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990935PMC
March 2020

High prevalence of mutations in perilipin 1 in patients with precocious acute coronary syndrome.

Atherosclerosis 2020 01 12;293:86-91. Epub 2019 Dec 12.

MARS Cardio, Mediterranean Association for Research and Studies in Cardiology, Intensive Care Unit, Hospital Nord, Marseille, France; Aix Marseille Univ, INSERM, INRA, C2VN, Marseille, France. Electronic address:

Background And Aims: Genetic partial lipodystrophies are rare heterogeneous disorders characterized by abnormalities of fat distribution and associated metabolic complications including a predisposition for atherosclerotic cardiovascular disease. We hypothesized that the milder forms of these diseases might be underdiagnosed and might result in early acute coronary syndrome (ACS) as the first sign of the pathology.

Methods: We performed targeted sequencing on a panel of 8 genes involved in genetic lipodystrophy for 62 patients with premature ACS, and selected heterozygous missense variations with low frequency. To confirm those results, we analyzed a second independent group of 60 additional patients through Sanger sequencing, and compared to a control group of 120 healthy patients.

Results: In the first cohort, only PLIN1 exhibited variants in more than 1 patient. In PLIN1, 3 different variants were found in 6 patients. We then analyzed PLIN1 sequence in the second cohort with premature ACS and found 2 other patients. Altogether, 8 patients were carriers of 4 different mutations in PLIN1. The variant frequencies in the total cohort of 122 patients were compared to frequencies observed in a local control cohort and in 2 different public databases showing a significant difference between patient vs control group frequencies for two mutations out of 4 (c.245C > T p = 10; c.839G > A p = 0.014).

Discussion: This is the first study that identifies a high frequency of potential pathogenic mutations in PLIN1 related to early onset ACS. These findings could contribute to the prevention and care of precocious ACS in families carrying those mutations.
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http://dx.doi.org/10.1016/j.atherosclerosis.2019.12.002DOI Listing
January 2020

Cost-Effectiveness of Drug-Eluting Stents in Elderly Patients With Coronary Artery Disease: The SENIOR Trial.

Value Health 2019 12 29;22(12):1355-1361. Epub 2019 Aug 29.

AP-HP URC Eco IdF, Unité de recherche clinique en économie de la santé d'Ile de France, Paris, France.

Background: Elderly patients receive bare metal stents instead of drug-eluting stents (DES) to shorten the duration of dual antiplatelet therapy (DAPT). The SENIOR trial compared outcomes between these 2 types of stents combined with a short duration of DAPT. A significant decrease in the number of patients with at least 1 major adverse cardiac and cerebrovascular event (MACCE) was noted in the DES group.

Objectives: The objective of this article was to perform an economic evaluation of the SENIOR trial.

Methods: This evaluation was performed separately in 5 participating countries using pooled patient-level data from all study patients and country-specific unit costs and utility values. Costs, MACCEs, and quality-adjusted life-years (QALYs) were calculated in both arms at 1 year, and an incremental cost-effectiveness ratio was estimated. Uncertainty was explored by probabilistic bootstrapping.

Results: A total of 1200 patients underwent randomization. The average total cost per patient was higher in the DES group. The number of MACCEs and average QALYs were not statistically different between the 2 groups. The 1-year incremental cost-effectiveness ratio for each country of reference ranged from €13 752 to €20 511/MACCE avoided and from €42 835 to €68 231/QALY gained. The scatter plots found a wide dispersion, reflecting a large uncertainty surrounding the results. But in each country studied, 90% of the bootstrap replications indicated a higher cost for greater effectiveness for the DES group. Assuming a willingness to pay of €50 000/QALY, there was between a 40% and 50% chance that the use of DES was cost-effective in 4 countries.

Conclusion: The use of DES instead of bare metal stents combined with a short duration of DAPT in elderly patients induced higher cost for greater effectiveness in each of the 5 countries studied.
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http://dx.doi.org/10.1016/j.jval.2019.07.008DOI Listing
December 2019

Femoral Versus Nonfemoral Peripheral Access for Transcatheter Aortic Valve Replacement.

J Am Coll Cardiol 2019 12;74(22):2728-2739

Paris Cardiovascular Research Center, INSERM Unit 970, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Cardiology Department, Paris, France.

Background: Femoral access is the gold standard for transcatheter aortic valve replacement (TAVR). Guidelines recommend reconsidering surgery when this access is not feasible. However, alternative peripheral accesses exist, although they have not been accurately compared with femoral access.

Objectives: This study compared nonfemoral peripheral (n-FP) TAVR with femoral TAVR.

Methods: Using the data from the national prospective French registry (FRANCE TAVI [French Transcatheter Aortic Valve Implantation]), this study compared the characteristics and outcomes of TAVR procedures according to whether they were performed through a femoral or a n-FP access, using a pre-specified propensity score-based matching between groups. Subanalysis during 2 study periods (2013 to 2015 and 2016 to 2017) and among low/intermediate-low and intermediate-high/high volume centers were performed.

Results: Among 21,611 patients, 19,995 (92.5%) underwent femoral TAVR and 1,616 (7.5%) underwent n-FP TAVR (transcarotid, n = 914 or trans-subclavian, n = 702). Patients in the n-FP access group had more severe disease (mean logistic EuroSCORE 19.95 vs. 16.95; p < 0.001), with a higher rate of peripheral vascular disease, known coronary artery disease, chronic pulmonary disease, and renal failure. After matching, there was no difference in the rate of post-procedural death and complications according to access site, except for a 2-fold lower rate of major vascular complications (odds ratio: 0.45; 95% confidence interval: 0.21 to 0.93; p = 0.032) and unplanned vascular repairs (odds ratio: 0.41; 95% confidence interval: 0.29 to 0.59; p < 0.001) in those who underwent n-FP access. The comparison of outcomes provided similar results during the second study period and in intermediate-high/high volume centers.

Conclusions: n-FP TAVR is associated with similar outcomes compared with femoral peripheral TAVR, except for a 2-fold lower rate of major vascular complications and unplanned vascular repairs. n-FP TAVR may be favored over surgery in patients who are deemed ineligible for femoral TAVR and may be a safe alternative when femoral access risk is considered too high.
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http://dx.doi.org/10.1016/j.jacc.2019.09.054DOI Listing
December 2019

Outcomes in nonagenarians undergoing transcatheter aortic valve implantation: a nationwide analysis.

EuroIntervention 2020 Apr;15(17):1489-1496

Cardiologie, CHU-Timone, Marseille, France.

Aims: The aim of this study was to describe the midterm outcomes in nonagenarians undergoing transcatheter aortic valve implantation (TAVI).

Methods And Results: Based on the French administrative hospital discharge database, the study collected information for all consecutive patients with aortic stenosis (AS), and specifically those treated with TAVI between 2010 and 2018. Cox regression was used for the analysis of predictors of events. We compared patients according to their age. Within the studied period, 71,095 patients older than 90 years with AS were identified. After matching on baseline characteristics, TAVI was associated with lower rates of a combined outcome of all-cause death, rehospitalisation for heart failure and stroke (relative risk [RR] 0.58, p<0.001) in comparison with matched nonagenarians with AS treated medically. During follow-up (median 161 days, interquartile range 13-625), the combined outcome occurred more frequently in nonagenarians (RR 1.22, p<0.01) who had a TAVI than in younger patients undergoing this procedure. All-cause death was reported in 17.6% versus 14.5% of nonagenarians, rehospitalisation for heart failure in 21.3% versus 18.2%, and stroke in 3.7% versus 2.9% (p<0.01 for all parameters). We identified the Charlson comorbidity index, heart failure, atrial fibrillation, stroke, vascular disease, cognitive impairment and denutrition as independent predictors of adverse outcomes in nonagenarians undergoing TAVI.

Conclusions: Among nonagenarians with AS, patients treated with TAVI had a lower risk of cardiovascular events than matched patients treated medically. The patients undergoing a TAVI at this age were often highly selected; the procedure was associated with acceptable long-term outcomes.
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http://dx.doi.org/10.4244/EIJ-D-19-00647DOI Listing
April 2020

Balloon-Expandable Versus Self-Expanding Transcatheter Aortic Valve Replacement: A Propensity-Matched Comparison From the FRANCE-TAVI Registry.

Circulation 2020 01 16;141(4):243-259. Epub 2019 Nov 16.

Département de Cardiologie, Institut Coeur Poumon, Inserm U1011, Institut Pasteur de Lille, EGID (E.V.B., F.V., N.D., A. Cosenza, G. Schurtz, S.P., E.R., A. Coisne, T. Modine, M.R., C.D.).

Background: No randomized study powered to compare balloon expandable (BE) with self expanding (SE) transcatheter heart valves (THVs) on individual end points after transcatheter aortic valve replacement has been conducted to date.

Methods: From January 2013 to December 2015, the FRANCE-TAVI nationwide registry (Registry of Aortic Valve Bioprostheses Established by Catheter) included 12 141 patients undergoing BE-THV (Edwards, n=8038) or SE-THV (Medtronic, n=4103) for treatment of native aortic stenosis. Long term mortality status was available in all patients (median 20 months; interquartile range, 14 to 30). Patients treated with BE-THV (n=3910) were successfully matched 1:1 with 3910 patients treated with SE-THV by using propensity score (25 clinical, anatomical, and procedural variables) and by date of the procedure (within 3 months). The first coprimary outcome was ≥ moderate occurrence of paravalvular regurgitation or in-hospital mortality, or both. The second coprimary outcome was 2-year all-cause mortality.

Results: In propensity-matched analyses, the incidence of the first coprimary outcome was higher with SE-THV (19.8%) compared with BE-THV (11.9%; relative risk, 1.68 [95% CI, 1.46-1.91]; <0.0001). Each component of the outcome was also higher in patients receiving SE-THV: ≥ moderate paravalvular regurgitation (15.5% versus 8.3%; relative risk, 1.90 [95% CI, 1.63-2.22]; <0.0001) and in hospital mortality (5.6% versus 4.2%; relative risk, 1.34 [95% CI, 1.07-1.66]; =0.01). During follow up, all cause mortality occurred in 899 patients treated with SE-THV (2-year mortality, 29.8%) and in 801 patients treated with BE-THV (2-year mortality, 26.6%; hazard ratio, 1.17 [95% CI, 1.06-1.29]; =0.003). Similar results were found using inverse probability of treatment weighting using propensity score analysis.

Conclusion: The present study suggests that use of SE-THV was associated with a higher risk of paravalvular regurgitation and higher in-hospital and 2-year mortality compared with use of BE-THV. These data strongly support the need for a randomized trial sufficiently powered to compare the latest generation of SE-THV and BE-THV.

Clinical Trial Registration: https://www.clinicaltrials.gov. Unique identifier: NCT01777828.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.043785DOI Listing
January 2020

Impact of Sapien 3 Balloon-Expandable Versus Evolut R Self-Expandable Transcatheter Aortic Valve Implantation in Patients With Aortic Stenosis: Data From a Nationwide Analysis.

Circulation 2020 01 16;141(4):260-268. Epub 2019 Nov 16.

Service d'information médicale, d'épidémiologie et d'économie de la santé, Unité d'épidémiologie hospitalière régionale (J.H., T.L., L.G.-G.), France.

Background: Two competing transcatheter aortic valve replacement (TAVR) technologies are currently available. Head-to-head comparisons of the relative performances of these 2 devices have been published. However, long-term clinical outcome evaluation remains limited by the number of patients analyzed, in particular, for recent-generation devices.

Methods: Based on the French administrative hospital-discharge database, the study collected information for all consecutive patients treated with a TAVR device commercialized in France between 2014 and 2018. Propensity score matching was used for the analysis of outcomes during follow-up. The objective of this study was to analyze the outcomes of TAVR according to Sapien 3 balloon-expandable (BE) versus Evolut R self-expanding TAVR technology at a nationwide level in France.

Results: A total of 31 113 patients treated with either Sapien 3 BE or Evolut R self-expanding TAVR were found in the database. After matching on baseline characteristics, 20 918 patients were analyzed (10 459 in each group with BE or self-expanding valves). During follow-up (mean [SD], 358 [384]; median [interquartile range], 232 [10-599] days), BE TAVR was associated with a lower yearly incidence of all-cause death (relative risk, 0.88; corrected =0.005), cardiovascular death (relative risk, 0.82; corrected =0.002), and rehospitalization for heart failure (relative risk, 0.84; corrected <0.0001). BE TAVR was also associated with lower rates of pacemaker implantation after the procedure (relative risk, 0.72; corrected <0.0001).

Conclusions: On the basis of the largest cohort available, we observed that Sapien 3 BE valves were associated with lower rates of all-cause death, cardiovascular death, rehospitalization for heart failure, and pacemaker implantation after a TAVR procedure.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.043971DOI Listing
January 2020

Reasons for the Failure of Platelet Function Testing to Adjust Antiplatelet Therapy: Pharmacodynamic Insights From the ARCTIC Study.

Circ Cardiovasc Interv 2019 11 7;12(11):e007749. Epub 2019 Nov 7.

Sorbonne University, ACTION Study Group, INSERM UMRS 1166, Cardiology Institute, Pitié-Salpêtrière (AP-HP) University Hospital, Paris, France (B.L., J.S., Y.Y., G.M., J.-P.C.).

Background: In the ARCTIC trial (Assessment by a Double Randomization of a Conventional Antiplatelet Strategy Versus a Monitoring-Guided Strategy for Drug-Eluting Stent Implantation and of Treatment Interruption Versus Continuation One Year After Stenting), treatment adjustment following platelet function testing failed to improve clinical outcomes. However, high-on-treatment platelet reactivity (HPR) is considered as a predictor of poor ischemic outcome. This prespecified substudy evaluated clinical outcomes according to the residual platelet reactivity status after antiplatelet therapy adjustment.

Methods: We analyzed the 1213 patients assigned to the monitoring arm of the ARCTIC trial in whom platelet reactivity was evaluated by the VerifyNow P2Y test before percutaneous coronary intervention and during the maintenance phase (at 14 days). HPR was defined as platelet reaction unit≥235U. The primary ischemic end point, a composite of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularization and the safety end point of major bleeding were assessed according to the platelet reactivity status.

Results: Before percutaneous coronary intervention, 35.7% of patients displayed HPR (n=419). During the acute phase, between percutaneous coronary intervention and the 14-day platelet function testing, ischemic (adjusted hazard ratio, 0.94 [95% CI, 0.74-1.18]; =0.58) and safety outcomes (hazard ratio, 1.28 [95% CI, 0.22-7.59]; =0.78) were similar in HPR and non-HPR patients. During the maintenance phase, the proportion of HPR patients (n=186, 17.4%) decreased by 56%. At 1-year, there was no difference for the ischemic end point (5.9% versus 6.0%; adjusted hazard ratio, 0.79 [95% CI, 0.40-1.58]; =0.51) and a nonsignificant higher rate of major bleedings (2.7% versus 1.0%, hazard ratio, 2.83 [95% CI, 0.96-8.41]; =0.06) in HPR versus non-HPR patients.

Conclusions: The proportion of HPR was halved after platelet function testing and treatment adjustment but without significant ischemic benefit at 1 year. HPR seems more as a modifiable risk marker than a risk factor of ischemic outcome.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00827411.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.118.007749DOI Listing
November 2019

Platelet CD40 ligand and bleeding during P2Y12 inhibitor treatment in acute coronary syndrome.

Res Pract Thromb Haemost 2019 Oct 26;3(4):684-694. Epub 2019 Jul 26.

Aix Marseille University INSERM, INRA, C2VN Marseille France.

Antiplatelet therapy through inhibition of the adenosine diphosphate (ADP)/P2Y12 pathway is commonly used in the treatment of acute coronary syndrome (ACS). Although efficient in preventing platelet activation and thrombus formation, it increases the risk of bleeding complications. In patients with ACS receiving platelet aggregation inhibitors, that is, P2Y12 blockers (n = 923), we investigated the relationship between plasma and platelet-associated CD40L levels and bleeding events (n = 71). Treatment with P2Y12 inhibitors in patients with ACS did not affect plasma-soluble CD40L levels, but decreased platelet CD40L surface expression (pCD40L) and platelet-released CD40L (rCD40L) levels in response to stimulation as compared to healthy controls. In vitro inhibition of the ADP pathway in healthy control platelets reduced both pCD40L and rCD40L levels. In a multivariable analysis, the reduced pCD40L level observed in ACS patients was significantly associated with the risk of bleeding occurrence (adjusted odds ratio = 0.15; 95% confidence interval = 0.034-0.67). P2Y12 inhibitor-treated (ticagrelor) mice exhibited a 2.5-fold increase in tail bleeding duration compared with controls. A significant reduction in bleeding duration was observed on CD40L but not CD40L platelet infusion. In addition, CD40L blockade in P2Y12 inhibitor-treated blood samples from a healthy human reduced thrombus growth over immobilized collagen under arterial flow. In conclusion, measurement of pCD40L may offer a novel approach to assessing bleeding risk in patients with ACS who are being treated with P2Y12 inhibitors.
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http://dx.doi.org/10.1002/rth2.12244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781928PMC
October 2019

Platelet reactivity inhibition following ticagrelor loading dose in patients undergoing percutaneous coronary intervention for acute coronary syndrome.

J Thromb Haemost 2019 12 27;17(12):2188-2195. Epub 2019 Jul 27.

Intensive Care Unit, Department of Cardiology, Assistance Publique-Hôpitaux de Marseille, Hôpital Nord, Aix-Marseille University, Marseille, France.

Background: Ticagrelor induces more potent platelet reactivity (PR) inhibition with reduced interindividual variability compared to clopidogrel. Although on-clopidogrel PR was shown to correlate with ischemia and bleeding events, no study has investigated the relationship between on-ticagrelor PR and outcome.

Objectives: We aimed to evaluate the relationship between on-ticagrelor PR, assessed by the vasodilator-stimulated phosphoprotein index (VASP), and thrombotic and bleeding events in patients with acute coronary syndrome (ACS) treated by percutaneous coronary intervention (PCI).

Methods: We performed a prospective, multicenter observational study on patients treated with PCI for ACS. The VASP index was used to assess PR after ticagrelor loading dose (LD). The primary endpoint was the link between major adverse cardiovascular events (MACE) and PR.

Results: Among the 530 patients with ACS included, 183 (34.5%) were admitted for ST elevation myocardial infarction. We observed high potency and limited interindividual variability after the ticagrelor LD (VASP 19.1% ± 16.6%). At 1 month, 21 (3.8%) MACE and 29 (5.5%) bleedings ≥ 2 according to the Bleedings Academic Research Consortium (BARC) scale were recorded. Neither MACE nor bleeding was associated with PR (P = .34 and P = .78, respectively). However, there was a strong association between PR and the occurrence of definite acute stent thrombosis (P = .03). Platelet reactivity was the only factor associated with acute definite stent thrombosis.

Conclusion: In patients receiving a ticagrelor LD while undergoing PCI for ACS, PR using the VASP did not predict MACE or bleeding, but it was significantly associated with the occurrence of definite acute stent thrombosis.
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http://dx.doi.org/10.1111/jth.14592DOI Listing
December 2019

Antithrombotics: From Aspirin to DOACs in Coronary Artery Disease and Atrial Fibrillation (Part 3/5).

J Am Coll Cardiol 2019 08 2;74(5):699-711. Epub 2019 Jul 2.

Duke Clinical Research Institute and Division of Cardiology, Duke University Medical Center, Durham, North Carolina.

For secondary prevention of coronary artery disease (CAD), oral antiplatelet therapy is essential. In case of coronary intervention, temporary dual antiplatelet therapy is mandatory as well. Recently, low-dose oral anticoagulation has entered the CAD arena. Atrial fibrillation (AF) is often seen in CAD and vice versa. In most patients stroke prevention in AF consists of oral anticoagulation. In many cases of CAD in patients with AF, anticoagulation has to be combined with antiplatelet agents (so called, dual pathway antithrombotic therapy). Excess bleeding in these conditions is a rapidly rising problem. This review addresses the antithrombotic options in CAD alone, in AF alone, and in their combination, when either an invasive or a noninvasive approach has been chosen.
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http://dx.doi.org/10.1016/j.jacc.2019.02.080DOI Listing
August 2019

Updated Expert Consensus Statement on Platelet Function and Genetic Testing for Guiding P2Y Receptor Inhibitor Treatment in Percutaneous Coronary Intervention.

JACC Cardiovasc Interv 2019 08 12;12(16):1521-1537. Epub 2019 Jun 12.

Division of Cardiology, University of Florida College of Medicine, Jacksonville, Florida. Electronic address:

Dual-antiplatelet therapy (DAPT) with aspirin and a P2Y receptor inhibitor is the standard treatment for patients undergoing percutaneous coronary intervention. The availability of different P2Y receptor inhibitors (clopidogrel, prasugrel, ticagrelor) with varying levels of potency has enabled physicians to contemplate individualized treatment regimens, which may include escalation or de-escalation of P2Y-inhibiting therapy. Indeed, individualized and alternative DAPT strategies may be chosen according to the clinical setting (stable coronary artery disease vs. acute coronary syndrome), the stage of the disease (early- vs. long-term treatment), and patient risk for ischemic and bleeding complications. A tailored DAPT approach may be potentially guided by platelet function testing (PFT) or genetic testing. Although the routine use of PFT or genetic testing in percutaneous coronary intervention-treated patients is not recommended, recent data have led to an update in guideline recommendations that allow considering selective use of PFT for DAPT de-escalation. However, guidelines do not expand on when to implement the selective use of such assays into decision making for personalized treatment approaches. Therefore, an international expert consensus group of key leaders from North America, Asia, and Europe with expertise in the field of antiplatelet treatment was convened. This document updates 2 prior consensus papers on this topic and summarizes the contemporary updated expert consensus recommendations for the selective use of PFT or genotyping in patients undergoing percutaneous coronary intervention.
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http://dx.doi.org/10.1016/j.jcin.2019.03.034DOI Listing
August 2019

Optimal duration of dual antiplatelet therapy post percutaneous coronary intervention in acute coronary syndrome.

Trends Cardiovasc Med 2020 05 31;30(4):198-202. Epub 2019 May 31.

Département de Cardiologie, CHU Timone, Marseille, F-13385 France; Aix-Marseille Université, Faculté de Médecine, F-13385, Marseille, France; Aix Marseille Univ, Inserm, Inra, C2VN, Marseille, France.

Dual antiplatelet therapy (DAPT), with aspirin plus a P2Y12 inhibitor agent, is the cornerstone treatment after percutaneous coronary intervention for acute coronary syndrome. Based on randomized clinical trial using aspirin and clopidogrel, a DAPT duration of 12 months has been recommended after an acute coronary syndrome. Despite the development of more potent antiplatelet agents (i.e. prasugrel and ticagrelor) and the reduction in ischemic recurrences after acute coronary syndrome, 12 months DAPT currently remains the gold standard. However, a significant proportion of patients experience recurrent ischemic events beyond the first 12 months after an acute coronary syndrome. Meanwhile, with more effective antiplatelet agent, bleeding has become a major safety concern on DAPT. Therefore, the ischemic and bleeding risk balance is central considering the duration of DAPT after an acute coronary syndrome. This review aims to report the evidence for an optimization and individualization of DAPT duration after an acute coronary syndrome.
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http://dx.doi.org/10.1016/j.tcm.2019.05.008DOI Listing
May 2020