Publications by authors named "Kensuke Matsushita"

46 Publications

Reply to "Patients with aortic stenosis exhibit early improved endothelial function following transcatheter aortic valve replacement: The eFAST study" by Comella et al.

Int J Cardiol 2021 Apr 30. Epub 2021 Apr 30.

Department of Cardiovascular Medicine, Nouvel Hôpital Civil, Strasbourg University Hospital, Strasbourg, France; INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine, FMTS, Strasbourg, France. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2021.04.058DOI Listing
April 2021

Letter by Carmona et al Regarding Article, "Beneficial Effect of Statins in COVID-19-Related Outcomes-Brief Report: a National Population-Based Cohort Study".

Arterioscler Thromb Vasc Biol 2021 05 21;41(5):e280-e281. Epub 2021 Apr 21.

Division of Cardiovascular Medicine, Strasbourg University Hospital, France (A.C., B.M., K.M., O.M.).

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http://dx.doi.org/10.1161/ATVBAHA.121.316224DOI Listing
May 2021

Incomplete Recovery From Takotsubo Syndrome Is a Major Determinant of Cardiovascular Mortality.

Circ J 2021 Apr 6. Epub 2021 Apr 6.

Université de Strasbourg, Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire.

Background: Although there is an apparent rapid and spontaneous recovery of left ventricular ejection fraction (LVEF) in patients with Takotsubo syndrome (TTS), recent studies have demonstrated a long-lasting functional impairment in those patients. The present study sought to evaluate the predictors of incomplete recovery following TTS and its impact on cardiovascular mortality.Methods and Results:Patients with TTS between 2008 and 2018 were retrospectively enrolled at 3 different institutions. After exclusion of in-hospital deaths, 407 patients were split into 2 subgroups according to whether their LVEF was >50% (recovery group; n=341), or ≤50% (incomplete recovery group; n=66) at the chronic phase. Multivariate logistic regression analysis found that LVEF (odds ratio [OR]: 0.94; 95% confidence interval [CI]: 0.91-0.98; P<0.001) and C-reactive protein levels (OR: 1.11; 95% CI: 1.02-1.22; P=0.02) at discharge were independent predictors of incomplete recovery. At a median follow up of 52 days, a higher cardiovascular mortality was evident in the incomplete recovery group (16% vs. 0.6%; P<0.001).

Conclusions: This study demonstrated that incomplete recovery after TTS is characterized by residual systemic inflammation and an increased cardiac mortality at follow up. Altogether, the present study findings determined that patients with persistent inflammation are a high-risk subgroup, and should be targeted in future clinical trials with specific therapies to attenuate inflammation.
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http://dx.doi.org/10.1253/circj.CJ-20-1116DOI Listing
April 2021

Discrepancy in Von Willebrand Abnormalities Between Degenerative and Functional Mitral Regurgitation.

Am J Cardiol 2021 Mar 14. Epub 2021 Mar 14.

Université de Strasbourg, Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Strasbourg, France.; UMR1260 INSERM, Nanomédecine Régénérative, Faculté de Pharmacie, Université de Strasbourg, Illkirch, France.

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http://dx.doi.org/10.1016/j.amjcard.2021.03.007DOI Listing
March 2021

Angiotensin II-induced upregulation of SGLT1 and 2 contributes to human microparticle-stimulated endothelial senescence and dysfunction: protective effect of gliflozins.

Cardiovasc Diabetol 2021 Mar 16;20(1):65. Epub 2021 Mar 16.

Regenerative Nanomedicine, Faculty of Pharmacy, UMR 1260, INSERM (French National Institute of Health and Medical Research), University of Strasbourg, 67000, Strasbourg, France.

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduced cardiovascular risk in type 2 diabetes patients independently of glycemic control. Although angiotensin II (Ang II) and blood-derived microparticles are major mediators of cardiovascular disease, their impact on SGLT1 and 2 expression and function in endothelial cells (ECs) and isolated arteries remains unclear.

Methods: ECs were isolated from porcine coronary arteries, and arterial segments from rats. The protein expression level was assessed by Western blot analysis and immunofluorescence staining, mRNA levels by RT-PCR, oxidative stress using dihydroethidium, nitric oxide using DAF-FM diacetate, senescence by senescence-associated beta-galactosidase activity, and platelet aggregation by aggregometer. Microparticles were collected from blood of patients with coronary artery disease (CAD-MPs).

Results: Ang II up-regulated SGLT1 and 2 protein levels in ECs, and caused a sustained extracellular glucose- and Na-dependent pro-oxidant response that was inhibited by the NADPH oxidase inhibitor VAS-2780, the AT1R antagonist losartan, sotagliflozin (Sota, SGLT1 and SGLT2 inhibitor), and empagliflozin (Empa, SGLT2 inhibitor). Ang II increased senescence-associated beta-galactosidase activity and markers, VCAM-1, MCP-1, tissue factor, ACE, and AT1R, and down-regulated eNOS and NO formation, which were inhibited by Sota and Empa. Increased SGLT1 and SGLT2 protein levels were observed in the rat aortic arch, and Ang II- and eNOS inhibitor-treated thoracic aorta segments, and were associated with enhanced levels of oxidative stress and prevented by VAS-2780, losartan, Sota and Empa. CAD-MPs promoted increased levels of SGLT1, SGLT2 and VCAM-1, and decreased eNOS and NO formation in ECs, which were inhibited by VAS-2780, losartan, Sota and Empa.

Conclusions: Ang II up-regulates SGLT1 and 2 protein expression in ECs and arterial segments to promote sustained oxidative stress, senescence and dysfunction. Such a sequence contributes to CAD-MPs-induced endothelial dysfunction. Since AT1R/NADPH oxidase/SGLT1 and 2 pathways promote endothelial dysfunction, inhibition of SGLT1 and/or 2 appears as an attractive strategy to enhance the protective endothelial function.
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http://dx.doi.org/10.1186/s12933-021-01252-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967961PMC
March 2021

The Effect of Transoesophageal Echocardiography on Treatment Change in a High-Volume Stroke Unit.

J Clin Med 2021 Feb 17;10(4). Epub 2021 Feb 17.

Division of Cardiovascular Medicine, Hôpital Civil, Strasbourg University Hospital, 67000 Strasbourg, France.

Background and purpose-current guidelines recommend the use of transesophageal echocardiography (TEE) in relation to cardio-embolic sources of stroke. Methods-by using an hospital-based cohort, we retrospectively analyzed consecutive patients with acute ischemic stroke (AIS), acute hemorrhagic stroke (AHS) and transient ischemic attack (TIA) who were admitted in Strasbourg Stroke Center, France between November 2017 to December 2018. TEE reports were screened for detection of potential cardiac sources of embolism and the subsequent change in medical management. We performed univariate and multivariate analyses to identify predictors of relevant TEE findings. Results-out of the 990 patients admitted with confirmed stroke, 432 patients (42.6%) underwent TEE. Patients with TEE were younger (62.8 ± 14.8 vs. 73.8, < 0.001), presented less comorbidities and lower stroke severity assessed by lower NIHSS (2 IQR (0-4) vs. 3 IQR (0-10), < 0.01) and Modified (1 IQR (0-1) vs. 1 (0-3), < 0.01). A total of 227 examinations (52.5%) demonstrated abnormal findings considered as potential cardiac sources of embolism and 31 examinations (7.1%) were followed by subsequent change in medical management. Age (HR: 0.948, 95% CI 0.923 to 0.974; < 0.001), previous AIS (HR: 3.542, 95% CI 1.290 to 9.722; = 0.01), previous TIA (HR: 7.830, CI 95% 2214 to 27,689; = 0.001) and superficial middle cerebral artery territory infarction (HR: 2.774, CI 95% 1.168-6.589; = 0.021) were strong independent predictors with change in medical management following TEE. Conclusions-additional TEE changed the medical course of stroke patients in 7.1% in a French high-volume stroke unit.
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http://dx.doi.org/10.3390/jcm10040805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922802PMC
February 2021

Life-threatening arrhythmias in anterior ST-segment elevation myocardial infarction patients treated by percutaneous coronary intervention: adverse impact of morphine.

Eur Heart J Acute Cardiovasc Care 2020 Oct 14. Epub 2020 Oct 14.

Université de Strasbourg, Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, BP 426, 67091 Strasbourg, France.

Aims: Important controversies remain concerning the determinants of life-threatening arrhythmias during ST-segment elevation myocardial infarction (STEMI) and their impact on late adverse events. This study sought to investigate which factors might facilitate ventricular tachycardia (VT) and ventricular fibrillation (VF), in a homogeneous population of anterior STEMI patients defined by abrupt left anterior descending coronary artery (LAD) occlusion and no collateral flow.

Methods And Results: The 967 patients, who entered into the CIRCUS (Does Cyclosporine ImpRove Clinical oUtcome in ST elevation myocardial infarction patients) study, were assessed for further analysis. Acute VT/VF was defined as VT (run of tachycardia >30 s either self-terminated or requiring electrical/pharmacological cardioversion) or VF documented by electrocardiogram or cardiac monitoring, during transportation to the cathlab or initial hospitalization. VT/VF was documented in 136 patients (14.1%). Patients with VT/VF were younger and had shorter time from symptom onset to hospital arrival. Site of LAD occlusion, thrombus burden, area at risk, pre-percutaneous coronary intervention Thrombolysis in Myocardial Infarction flow, and ST-segment resolution were similar to that of patients without VT/VF. There was no impact of VT/VF on left ventricular remodelling or clinical outcomes. By multivariate analysis, the use of morphine (odds ratio 1.71; 95% confidence interval (1.13-2.60); P = 0.012) was the sole independent predictor of VT/VF occurrence.

Conclusions: In STEMI patients with LAD occlusion, our findings support the view that morphine could favour severe ventricular arrhythmias.
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http://dx.doi.org/10.1093/ehjacc/zuaa005DOI Listing
October 2020

Electrocardiographic Strain Pattern Is a Major Determinant of Rehospitalization for Heart Failure After Transcatheter Aortic Valve Replacement.

J Am Heart Assoc 2021 Feb 17;10(3):e014481. Epub 2021 Jan 17.

Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire Nouvel Hôpital CivilCentre Hospitalier UniversitaireUniversité de Strasbourg Strasbourg France.

Background Electrocardiographic strain pattern (ESP) has recently been associated with increased adverse outcome in aortic stenosis and after surgical aortic valve replacement. Our study sought to determine the impact and incremental value of ESP pattern in predicting adverse outcome after transcatheter aortic valve replacement. Methods and Results A total of 585 patients with severe aortic stenosis (mean age, 83±7 years; men, 39.8%) were enrolled for transcatheter aortic valve replacement from November 2012 to May 2018. ESP was defined as ≥1-mm concave down-sloping ST-segment depression and asymmetrical T-wave inversion in the lateral leads. The primary end points of the study were all-cause mortality, rehospitalization for heart failure, myocardial infarction, and stroke. A total of 178 (30.4%) patients were excluded because of left bundle-branch block (n=103) or right bundle-branch block (n=75). Among the 407 remaining patients, 106 had ESP (26.04%). At a median follow-up of 20.00 months (11.70-29.42 months), no impact of electric strain on overall and cardiac death could be established. By contrast, incidence of rehospitalization for heart failure was significantly higher (33/106 [31.1%] versus 33/301 [11%]; <0.001) in patients with ESP. By multivariate analyses, ESP remained a strong predictor of rehospitalization for heart failure (hazard ratio, 2.75 [95% CI, 1.61-4.67]; <0.001). Conclusions In patients with aortic stenosis who were eligible for transcatheter aortic valve replacement, ESP is frequent and associated with an increased risk of postinterventional heart failure regardless of preoperative left ventricular hypertrophy. ESP represents an easy, objective, reliable, and low-cost tool to identify patients who may benefit from intensified postinterventional follow-up.
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http://dx.doi.org/10.1161/JAHA.119.014481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955442PMC
February 2021

Effective Orifice Area of Balloon-Expandable and Self-Expandable Transcatheter Aortic Valve Prostheses: An Echo Doppler Comparative Study.

J Clin Med 2021 Jan 7;10(2). Epub 2021 Jan 7.

Pôle d'Activité Médico-Chirurgicale Cardiovasculaire, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France.

Published data on the size-specific effective orifice area (EOA) of transcatheter heart valves (THVs) remain scarce. Here, we sought to investigate the intra-individual changes in EOA and mean transvalvular aortic gradient (MG) of the Sapien 3 (S3), CoreValve (CV), and Evolut R (EVR) prostheses both at short-term and at 1-year follow-up. The study sample consisted of 260 consecutive patients with severe aortic stenosis who underwent transcatheter aortic valve implantation (TAVI). EOAs and MGs were measured with Doppler echocardiography for the following prostheses: S3 23 mm ( = 74; 28.5%), S3 26 mm ( = 67; 25.8%), S3 29 mm ( = 20; 7.7%), CV 23 mm ( = 2; 0.8%), CV 26 mm ( = 15; 5.8%), CV 29 mm ( = 24; 9.2%), CV 31 mm ( = 9; 3.5%), EVR 26 mm ( = 22; 8.5%), and EVR 29 mm ( = 27; 10.4%). Values were obtained at discharge, 1 month, 6 months, and 1 year from implantation. At discharge, EOAs were larger and MGs lower for larger-size prostheses, regardless of being balloon-expandable or self-expandable. In patients with small aortic annulus size, the hemodynamic performances of CV and EVR prostheses were superior to those of S3. However, we did not observe significant differences in terms of all-cause mortality according to THV type or size. Both balloon-expandable and self-expandable new-generation THVs show excellent hemodynamic performances without evidence of very early valve degeneration.
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http://dx.doi.org/10.3390/jcm10020186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825656PMC
January 2021

D-Dimers Level as a Possible Marker of Extravascular Fibrinolysis in COVID-19 Patients.

J Clin Med 2020 Dec 24;10(1). Epub 2020 Dec 24.

Division of Cardiovascular Medicine, Nouvel Hôpital Civil, Strasbourg University Hospital, 67000 Strasbourg, France.

Background And Objective: Host defence mechanisms to counter virus infection include the activation of the broncho-alveolar haemostasis. Fibrin degradation products secondary to extravascular fibrin breakdown could contribute to the marked increase in D-Dimers during COVID-19. We sought to examine the prognostic value on lung injury of D-Dimers in non-critically ill COVID-19 patients without thrombotic events.

Methods: This study retrospectively analysed hospitalized COVID-19 patients classified according to a D-Dimers threshold following the COVID-19 associated haemostatic abnormalities (CAHA) classification at baseline and at peak (Stage 1: D-Dimers less than three-fold above normal; Stage 2: D-Dimers three- to six-fold above normal; Stage 3: D-Dimers six-fold above normal). The primary endpoint was the occurrence of critical lung injuries on chest computed tomography. The secondary outcome was the composite of in-hospital death or transfer to the intensive care unit (ICU).

Results: Among the 123 patients included, critical lung injuries were evidenced in 8 (11.9%) patients in Stage 1, 6 (20%) in Stage 2 and 15 (57.7%) in Stage 3 ( = 0.001). D-Dimers staging at peak was an independent predictor of critical lung injuries regardless of the inflammatory burden assessed by CRP levels (OR 2.70, 95% CI (1.50-4.86); < 0.001) and was significantly associated with increased in-hospital death or ICU transfer (14.9 % in Stage 1, 50.0% in Stage 2 and 57.7% in Stage 3 ( < 0.001)). D-Dimers staging at peak was an independent predictor of in-hospital death or ICU transfer (OR 2.50, CI 95% (1.27-4.93); = 0.008).

Conclusions: In the absence of overt thrombotic events, D-Dimers quantification is a relevant marker of critical lung injuries and dismal patient outcome.
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http://dx.doi.org/10.3390/jcm10010039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795726PMC
December 2020

Risk and Severity of COVID-19 and ABO Blood Group in Transcatheter Aortic Valve Patients.

J Clin Med 2020 Nov 22;9(11). Epub 2020 Nov 22.

Division of Cardiovascular Medicine, Strasbourg University Hospital, 67000 Strasbourg, France.

While cardiovascular disease has been associated with an increased risk of coronavirus disease 2019 (COVID-19), no studies have described its clinical course in patients with aortic stenosis who had undergone transcatheter aortic valve replacement (TAVR). Numerous observational studies have reported an association between the A blood group and an increased susceptibility to SARS-CoV-2 infection. Our objective was to investigate the frequency and clinical course of COVID-19 in a large sample of patients who had undergone TAVR and to determine the associations of the ABO blood group with disease occurrence and outcomes. Patients who had undergone TAVR between 2010 and 2019 were included in this study and followed-up through the recent COVID-19 outbreak. The occurrence and severity (hospitalization and/or death) of COVID-19 and their associations with the ABO blood group served as the main outcome measures. Of the 1125 patients who had undergone TAVR, 403 (36%) died before 1 January 2020, and 20 (1.8%) were lost to follow-up. The study sample therefore consisted of 702 patients. Of them, we identified 22 cases (3.1%) with COVID-19. Fourteen patients (63.6%) were hospitalized or died of disease. Multivariable analysis identified the A blood group (vs. others) as the only independent predictor of COVID-19 in patients who had undergone TAVR (odds ratio (OR) = 6.32; 95% confidence interval (CI) = 2.11-18.92; = 0.001). The A blood group (vs. others; OR = 8.27; 95% CI = 1.83-37.43, = 0.006) and a history of cancer (OR = 4.99; 95% CI = 1.64-15.27, = 0.005) were significantly and independently associated with disease severity (hospitalization and/or death). We conclude that patients who have undergone TAVR frequently have a number of cardiovascular comorbidities that may work to increase the risk of COVID-19. The subgroup with the A blood group was especially prone to developing the disease and showed unfavorable outcomes.
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http://dx.doi.org/10.3390/jcm9113769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700222PMC
November 2020

Impact of residual inflammation on myocardial recovery and cardiovascular outcome in Takotsubo patients.

ESC Heart Fail 2021 Feb 18;8(1):259-269. Epub 2020 Nov 18.

Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Université de Strasbourg, BP 426, Strasbourg, 67091, France.

Aims: Recent insights have emphasized the importance of myocardial and systemic inflammation in Takotsubo syndrome (TTS). In a large registry of unselected patients, we sought to evaluate whether residual high inflammatory response (RHIR) could impact cardiovascular outcome after TTS.

Methods And Results: Patients with TTS were retrospectively included between 2008 and 2018 in three general hospitals. Three hundred eighty-five patients with TTS were split into three subgroups, according to tertiles of C-reactive protein (CRP) levels at discharge (CRP <5.2 mg/L, CRP range 5.2 to 19 mg/L, and CRP >19 mg/L). The primary endpoint was the impact of RHIR, defined as CRP >19 mg/L at discharge, on cardiac death or hospitalization for heart failure. Follow up was obtained in 382 patients (99%) after a median of 747 days. RHIR patients were more likely to have a history of cancer or a physical trigger. Left ventricular ejection fraction (LVEF) at admission and at discharge were comparable between groups. By contrast, RHIR was associated with lower LVEF at follow up (61.7% vs. 60.7% vs. 57.9%; P = 0.004) and increased cardiac late mortality (0% vs. 0% vs. 10%; P = 0.001). By multivariate Cox regression analysis, RHIR was an independent predictor of cardiac death or hospitalization for heart failure (hazard ratio: 1.87; 95% confidence interval: 1.08 to 3.25; P = 0.025).

Conclusions: Residual high inflammatory response was associated with impaired LVEF at follow up and was evidenced as an independent factor of cardiovascular events. All together, these findings underline RHIR patients as a high-risk subgroup, to target in future clinical trials with specific therapies to attenuate RHIR.
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http://dx.doi.org/10.1002/ehf2.12945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835625PMC
February 2021

Increased susceptibility to SARS-CoV-2 infection in patients with reduced left ventricular ejection fraction.

ESC Heart Fail 2021 02 18;8(1):380-389. Epub 2020 Nov 18.

Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Université de Strasbourg, Strasbourg, France.

Aims: Cardiovascular disease has been recognized as a major determinant of coronavirus disease 2019 (COVID-19) vulnerability and severity. Angiotensin-converting enzyme (ACE) 2 is a functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is up-regulated in patients with heart failure. We sought to examine the potential association between reduced left ventricular ejection fraction (LVEF) and the susceptibility to SARS-CoV-2 infection.

Methods And Results: Of the 1162 patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention between February 2014 and October 2018, we enrolled 889 patients with available clinical follow-up data. Follow-up was conducted by telephone interviews 1 month after the start of the French lockdown which began on 17 March 2020. Patients were divided into two groups according to LVEF <40% (reduced LVEF) (n = 91) or ≥40% (moderately reduced + preserved LVEF) (n = 798). The incidence of COVID-19-related hospitalization or death was significantly higher in the reduced LVEF group as compared with the moderately reduced + preserved LVEF group (9% vs. 1%, P < 0.001). No association was found between discontinuation of ACE-inhibitor or angiotensin-receptor blockers and COVID-19 test positivity. By multivariate logistic regression analysis, reduced LVEF was an independent predictor of COVID-19 hospitalization or death (odds ratio: 6.91, 95% confidence interval: 2.60 to 18.35, P < 0.001).

Conclusions: In a large cohort of patients with previous ACS, reduced LVEF was associated with increased susceptibility to COVID-19. Aggressive COVID-19 testing and therapeutic strategies may be considered for patient with impaired heart function.
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http://dx.doi.org/10.1002/ehf2.13083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753539PMC
February 2021

Clinical features of patients with acute coronary syndrome during the COVID-19 pandemic.

J Thromb Thrombolysis 2020 Nov 16. Epub 2020 Nov 16.

Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Université de Strasbourg, 1 place de l'Hôpital, 67091, Strasbourg cedex, France.

Although a reduction in hospital admissions of acute coronary syndromes (ACS) patients has been observed globally during the coronavirus disease 2019 (COVID-19) pandemic, clinical features of those patients have not been fully investigated. The aim of the present analysis is to investigate the incidence, clinical presentation, and outcomes of patients with ACS during the COVID-19 pandemic. We performed a retrospective analysis of consecutive patients who were admitted for ACS at our institution between March 1 and April 20, 2020 and compared with the equivalent period in 2019. Admissions for acute myocardial infarction (AMI) reduced by 39.5% in 2020 compared with the equivalent period in 2019. Owing to the emergency medical services (EMS) of our region, all time components of ST-elevated myocardial infarction care were similar during the COVID-19 outbreak as compared with the previous year's dataset. Among the 106 ACS patients in 2020, 7 patients tested positive for COVID-19. Higher incidence of type 2 myocardial infarction (29% vs. 4%, p = 0.0497) and elevated D-dimer levels (5650 μg/l [interquartile range (IQR) 1905-13,625 μg/l] vs. 400 μg/l [IQR 270-1050 μg/l], p = 0.02) were observed in COVID-19 patients. In sum, a significant reduction in admission for AMI was observed during the COVID-19 pandemic. COVID-19 patients were characterized by elevated D-dimer levels on admission, reflecting enhanced COVID-19 related thrombogenicity. The prehospital evaluation by EMS may have played an important role for the timely revascularization for STEMI patients.
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http://dx.doi.org/10.1007/s11239-020-02340-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668406PMC
November 2020

Value of Cardiac Biomarkers in the Early Diagnosis of Takotsubo Syndrome.

J Clin Med 2020 Sep 15;9(9). Epub 2020 Sep 15.

Université de Strasbourg, Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, 67091 Strasbourg, France.

Background: Bedside diagnosis between Takotsubo syndrome (TTS) and ST elevation (STEMI) and non-ST elevation (NSTEMI) myocardial infarction remains challenging. We sought to determine a cardiac biomarker profile to enable their early distinction.

Methods: 1100 patients (TTS = 314, STEMI = 452, NSTEMI = 334) were enrolled in two centers. Baseline clinical and biological characteristics were compared between groups.

Results: At admission, cut-off values of BNP (B-type natriuretic peptide)/TnI (Troponin I) ratio of 54 and 329 distinguished respectively STEMI from NSTEMI, and NSTEMI from TTS. Best differentiation was obtained by the use of BNP/TnI ratio at peak (cut-of values of 6 and 115 discriminated respectively STEMI from NSTEMI, and NSTEMI from TTS). We developed a score including five parameters (age, gender, history of psychiatric disorders, LVEF, and BNP/TnI ratio at admission) enabling good distinction between TTS and STEMI (77% specificity and 92% sensitivity, AUC 0.93). For the distinction between TTS and NSTEMI, a four variables score (gender, history of psychiatric disorders, LVEF, and BNP at admission) achieved a good diagnostic performance (89% sensitivity, 85% specificity, AUC 0.94).

Conclusion: A distinctive cardiac biomarker profile enables at an early stage a differentiation between TTS and ACS. A four (NSTEMI) or five variables score (STEMI) permitted a better discrimination.
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http://dx.doi.org/10.3390/jcm9092985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564647PMC
September 2020

Periprocedural Predictors of New-Onset Conduction Abnormalities After Transcatheter Aortic Valve Replacement.

Circ J 2020 09 1;84(10):1875-1883. Epub 2020 Sep 1.

Université de Strasbourg, Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire.

Background: New-onset conduction abnormalities (CAs) following transcatheter aortic valve replacement (TAVR) are associated with hospital rehospitalization and long-term mortality, but available predictors are sparse. This study sought to determine clinical predictors of new-onset left bundle branch block (LBBB) and new permanent pacemaker (PPM) implantation in patients undergoing TAVR.Methods and Results:We enrolled 290 patients who received SAPIEN 3 (Edwards Lifesciences, Irvine, CA, USA; n=217) or Evolut R (Medtronic, Minneapolis, MN, USA; n=73) from a prospective registry at Nouvel Hôpital Civil, Strasbourg, France between September 2014 and February 2018. Of 242 patients without pre-existing LBBB, 114 (47%) experienced new-onset LBBB and/or new PPM implantation. A difference between membranous septal length and implantation depth (∆MSID) was the only predictor of CAs for both types of valves. In the multivariate analysis, PR interval and ∆MSID remained as sole predictors of CAs. The risk for adverse clinical events, including all-cause death, myocardial infarction, stroke, and heart failure hospitalization, was higher for patients with CAs as compared with patients without CAs (hazard ratio: 2.10; 95% confidence interval: 1.26 to 3.57; P=0.004).

Conclusions: Computed tomography assessment of membranous septal anatomy and implantation depth predicted CAs after TAVR with new-generation valves. Future studies are required to identify whether adjustment of the implantation depth can reduce the risk of CAs and adverse clinical outcomes.
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http://dx.doi.org/10.1253/circj.CJ-20-0257DOI Listing
September 2020

Staging Severity of COVID-19 according to Hemostatic Abnormalities (CAHA Score).

Thromb Haemost 2020 Dec 30;120(12):1716-1719. Epub 2020 Aug 30.

Division of Cardiovascular Medicine, Nouvel Hôpital Civil, Strasbourg University Hospital, Strasbourg, France.

This is the first study to show a stepwise increase in venous thrombotic events according to COVID-19 coagulopathy (COVID-19-associated hemostatic abnormalities [CAHA]) staging and lung injuries assessed by chest computed tomography. Excess mortality and/or transfer to intensive care unit according to CAHA staging.
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http://dx.doi.org/10.1055/s-0040-1715836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869051PMC
December 2020

Predictive Impact of Paravalvular Leak Assessments on Clinical Outcomes Following Transcatheter Aortic Valve Replacement.

Am J Cardiol 2020 11 25;135:181-182. Epub 2020 Aug 25.

Université de Strasbourg, Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Strasbourg, France; UMR1260 INSERM, Nanomédecine Régénérative, Faculté de Pharmacie, Université de Strasbourg, Illkirch, France. Electronic address:

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http://dx.doi.org/10.1016/j.amjcard.2020.08.006DOI Listing
November 2020

Accordion phenomenon in the descending aorta during transcatheter aortic valve replacement followed by mesenteric ischaemia.

Eur Heart J 2020 08;41(29):2819

Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Université de Strasbourg, 1 place de l'Hôpital - 67091 Strasbourg, France.

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http://dx.doi.org/10.1093/eurheartj/ehz793DOI Listing
August 2020

Paradoxical Increase of Stroke in Patients with Defect of High Molecular Weight Multimers of the von Willebrand Factors following Transcatheter Aortic Valve Replacement.

Thromb Haemost 2020 Sep 29;120(9):1330-1338. Epub 2020 Jul 29.

Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Université de Strasbourg, Strasbourg, France.

Background:  Stroke is a major cause of disability after transcatheter aortic valve replacement (TAVR) and stroke prediction models and data are crucially needed. Following TAVR, high molecular weight (HMW) multimers defect of von Willebrand factor (VWF) as assessed by closure time of adenosine diphosphate (CT-ADP) value > 180 seconds is an independent predictor of bleeding events. This study sought to identify predictors of ischemic neurological events in patients who underwent TAVR and the specific impact of HMW multimers defect of VWF.

Methods:  Patients were prospectively enrolled between November 2012 and May 2018 at our institution. The CT-ADP, a point-of-care measure of hemostasis, was assessed the day before and 24 hours after the procedures. The rate of ischemic stroke and transient ischemic attack (TIA) was recorded up to 30 days after the procedures.

Results:  Of 565 TAVR patients, ischemic stroke/TIA was observed in 21 (3.7%) patients within 30 days. Ischemic stroke/TIA was associated with major/life-threatening bleeding complications (MLBCs) (9 [43%] vs. 88 [16%],  = 0.002) and postprocedure CT-ADP > 180 seconds (10 [48%] vs. 116 [21%],  = 0.01). By multivariate analysis, MLBCs (odds ratio [OR]: 3.58; 95% confidence interval [CI]: 1.45-8.84;  = 0.006) and postprocedure CT-ADP > 180 seconds (OR: 3.38; 95% CI: 1.38-8.25;  = 0.008) were evidenced as independent predictors of ischemic stroke/TIA.

Conclusion:  MLBCs and CT-ADP > 180 seconds were identified as predictors for ischemic stroke or TIA. The present study suggests that the defects of HMW multimers of the VWFs may contribute not only to bleeding events but also to thrombotic events.
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http://dx.doi.org/10.1055/s-0040-1713424DOI Listing
September 2020

Impact of Incomplete Coronary Revascularization on Late Ischemic and Bleeding Events after Transcatheter Aortic Valve Replacement.

J Clin Med 2020 Jul 16;9(7). Epub 2020 Jul 16.

Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Université de Strasbourg, 67000 Strasbourg, France.

Background: The impact of coronary artery disease (CAD) and revascularization by percutaneous coronary intervention (PCI) on prognosis in patients undergoing transcatheter aortic valve replacement (TAVR) remain debated. A dismal prognosis in patients undergoing PCI has been associated with elevated baseline SYNTAX score (bSS) and residual SYNTAX score (rSS). The objective was to investigate whether the degree of bSS and rSS impacted ischemic and bleeding events after TAVR.

Methods: bSS and rSS were calculated in 311 patients admitted for TAVR. The primary outcome was the occurrence of major adverse cardiac events (MACE), a composite endpoint of myocardial infarction, stroke, cardiovascular death, or rehospitalization for heart failure. The occurrence of late major/life-threatening bleeding complications (MLBCs) and each primary endpoint individually were the secondary endpoints.

Results: bSS > 22 was associated with higher occurrence of MACE ( = 0.013). rSS > 8 and bSS > 22 had no impact on overall cardiovascular mortality. rSS > 8 and bSS > 22 were associated with higher rates of myocardial infarction ( = 0.001 and = 0.004) and late occurrence of MLBCs. Multivariate analysis showed that bSS > 22 (sHR 2.48) and rSS > 8 (sHR 2.35) remained predictors of MLBCs but not of myocardial infarction.

Conclusions: Incomplete coronary revascularization and CAD burden did not impact overall and cardiac mortality but constitute predictors of late MLBCs in TAVR patients.
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http://dx.doi.org/10.3390/jcm9072267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408638PMC
July 2020

Venous thromboembolism in non-critically ill patients with COVID-19 infection.

Thromb Res 2020 09 17;193:166-169. Epub 2020 Jul 17.

Division of Cardiovascular Medicine, Nouvel Hôpital Civil, Strasbourg University Hospital, Strasbourg, France; INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine, FMTS, Strasbourg, France. Electronic address:

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http://dx.doi.org/10.1016/j.thromres.2020.07.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367026PMC
September 2020

Thromboprophylaxis: balancing evidence and experience during the COVID-19 pandemic.

J Thromb Thrombolysis 2020 Nov;50(4):799-808

Division of Cardiovascular Medicine, Nouvel Hôpital Civil, Strasbourg University Hospital, 1 place de l'Hôpital, 67000, Strasbourg, France.

A common and potent consideration has recently entered the landscape of the novel coronavirus disease of 2019 (COVID-19): venous thromboembolism (VTE). COVID-19 has been associated to a distinctive related coagulopathy that shows unique characteristics. The research community has risen to the challenges posed by this « evolving COVID-19 coagulopathy » and has made unprecedented efforts to promptly address its distinct characteristics. In such difficult time, both national and international societies of thrombosis and hemostasis released prompt and timely responses to guide recognition and management of COVID-19-related coagulopathy. However, latest guidelines released by the international Society on Thrombosis and Haemostasis (ISTH) on May 27, 2020, followed the American College of Chest Physicians (CHEST) on June 2, 2020 showed some discrepancies regarding thromboprophylaxis use. In this forum article, we would like to offer an updated focus on thromboprophylaxis with current incidence of VTE in ICU and non-ICU patients according to recent published studies; highlight the main differences regarding ISTH and CHEST guidelines; summarize and describe which are the key ongoing RCTs testing different anticoagulation strategies in patients with COVID-19; and finally set a proposal for COVID-19 coagulopathy specific risk factors and dedicated trials.
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http://dx.doi.org/10.1007/s11239-020-02231-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372740PMC
November 2020

COVID-19 Related Coagulopathy: A Distinct Entity?

J Clin Med 2020 May 31;9(6). Epub 2020 May 31.

Université de Strasbourg, Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, 67000 Strasbourg, France.

The coronavirus disease 2019 (COVID-19) pandemic has impacted healthcare communities across the globe on an unprecedented scale. Patients have had diverse clinical outcomes, but those developing COVID-19-related coagulopathy have shown a disproportionately worse outcome. This narrative review summarizes current evidence regarding the epidemiology, clinical features, known and presumed pathophysiology-based models, and treatment guidance regarding COVID-19 coagulopathy.
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http://dx.doi.org/10.3390/jcm9061651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356260PMC
May 2020

Impact of COVID-19 on the Cardiovascular System: A Review.

J Clin Med 2020 May 9;9(5). Epub 2020 May 9.

Université de Strasbourg, Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, 67091 Strasbourg, France.

The recent outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 has been declared a public health emergency of international concern. COVID-19 may present as acute respiratory distress syndrome in severe cases, and patients with pre-existing cardiovascular comorbidities are reported to be the most vulnerable. Notably, acute myocardial injury, determined by elevated high-sensitivity troponin levels, is commonly observed in severe cases, and is strongly associated with mortality. Therefore, understanding the effects of COVID-19 on the cardiovascular system is essential for providing comprehensive medical care for critically ill patients. In this review, we summarize the rapidly evolving data and highlight the cardiovascular considerations related to COVID-19.
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http://dx.doi.org/10.3390/jcm9051407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291320PMC
May 2020

Bedside Renal Doppler Ultrasonography and Acute Kidney Injury after TAVR.

J Clin Med 2020 Mar 25;9(4). Epub 2020 Mar 25.

Université de Strasbourg, Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, 67000 Strasbourg, France.

Acute kidney injury (AKI) following transcatheter aortic valve replacement (TAVR) is associated with a dismal prognosis. Elevated renal resistive index (RRI), through renal Doppler ultrasound (RDU) evaluation, has been associated with AKI development and increased systemic arterial stiffness. Our pilot study aimed to investigate the performance of Doppler based RRI to predict AKI and outcomes in TAVR patients. From May 2018 to May 2019, 100 patients with severe aortic stenosis were prospectively enrolled for TAVR and concomitant RDU evaluation at our institution (Nouvel Hôpital Civil, Strasbourg University, France). AKI by serum Creatinine (sCr-AKI) was defined according to the VARC-2 definition and AKI by serum Cystatin C (sCyC-AKI) was defined as an sCyC increase of greater than 15% with baseline value. Concomitant RRI measurements as well as renal and systemic hemodynamic parameters were recorded before, one day, and three days after TAVR. It was found that 10% of patients presented with AKI and AKI. The whole cohort showed higher baseline RRI values (0.76 ± 0.7) compared to normal known and accepted values. AKI had significant higher post-procedural RRI one day (Day 1) after TAVR (0.83 ± 0.1 vs. 0.77 ± 0.6, CI 95%, = 0.005). AUC for AKI was 0.766 and a RRI cut-off value of ≥ 0.795 had the most optimal sensitivity/specificity (80/62%) combination. By univariate Cox analysis, Mehran Risk Score, higher baseline right atrial pressure at baseline > 0.8 RRI values one day after TAVR (HR 6.5 (95% CI 1.3-32.9; = 0.021) but not RRI at baseline were significant predictors of AKI. Importantly, no significant impact of baseline biological parameters, renal or systemic parameters could be demonstrated. Doppler-based RRI can be helpful for the non-invasive assessment of AKI development after TAVR.
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http://dx.doi.org/10.3390/jcm9040905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230258PMC
March 2020

Systemic Inflammatory Response Syndrome Is a Major Determinant of Cardiovascular Outcome in Takotsubo Syndrome.

Circ J 2020 03 7;84(4):592-600. Epub 2020 Mar 7.

Department of Cardiology, Nouvel Hopital Civil, University Hospital of Strasbourg.

Background: Recent insights have emphasized the importance of inflammatory response in takotsubo syndrome (TTS). We sought to evaluate the predictors of systemic inflammatory response syndrome (SIRS) and its impact on cardiovascular mortality after TTS.Methods and Results:The 215 TTS patients were retrospectively included between September 2008 and January 2018. SIRS was diagnosed in 96 patients (44.7%). They had lower left ventricular ejection fraction (LVEF) on admission (34.5% vs. 41.9%; P<0.001) and higher peak brain natriuretic peptide and troponin. At a median follow-up of 518 days, SIRS was associated with increased in-hospital mortality (14.6% vs. 5.0%; P=0.019), overall mortality (29.4% vs. 10.8%; P=0.002), and cardiovascular mortality (10.6% vs. 2.1%; P=0.026). A history of cancer (OR, 3.36; 95% CI: 1.54-7.31; P=0.002) and LVEF <40% at admission (OR, 2.31; 95% CI: 1.16-4.58; P=0.017) were identified as independent predictors of SIRS. On multivariate Cox regression analysis, SIRS (HR, 12.8; 95% CI: 1.58-104; P=0.017), age (HR, 1.09; 95% CI: 1.02-1.16; P=0.01), and LVEF <40% at discharge (HR, 9.88; 95% CI: 2.54-38.4; P=0.001) were independent predictors of cardiovascular death.

Conclusions: SIRS was found in a large proportion of TTS patients and was associated with enhanced myocardial damage and adverse outcome in the acute phase. At long-term follow-up, SIRS remained an independent factor of cardiovascular death.
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http://dx.doi.org/10.1253/circj.CJ-19-1088DOI Listing
March 2020

Impact of serum lipoprotein (a) level on coronary plaque progression and cardiovascular events in statin-treated patients with acute coronary syndrome: a yokohama-acs substudy.

J Cardiol 2020 07 7;76(1):66-72. Epub 2020 Feb 7.

Division of Cardiology, Yokohama City University Medical Center, Yokohama, Japan.

Background: Lipoprotein (a) [Lp(a)] has been reported to be a residual risk factor in patients who have achieved target lipid levels. The aim of the present study was to investigate the associations of Lp(a) with plaque progression and major cardiovascular events in patients with acute coronary syndromes (ACS).

Methods: The Yokohama-ACS study included 102 patients with ACS who underwent intravascular ultrasound (IVUS) at baseline and at 10-month follow-up after percutaneous coronary intervention (PCI). The patients were randomly assigned to receive either moderate- or low-intensity statin therapy. IVUS was performed to measure the plaque volume at non-culprit lesions. We enrolled 76 patients for whom Lp(a) levels at 10-month follow-up were available.

Results: The patients were divided into 2 groups according whether their Lp(a) levels were ≤20 mg/dl [low Lp(a) group; n = 49] or >20 mg/dl [high Lp(a) group; n = 27]. Baseline characteristics and low-density lipoprotein cholesterol levels at 10-month follow-up were similar in the low Lp(a) group and high Lp(a) group (87 ± 29 mg/dl vs. 93 ± 27 mg/dl, p = 0.42). The low Lp(a) group had significant plaque regression, whereas the high Lp(a) group showed slight plaque progression (-6.8% vs. 2.5%, p = 0.02). Ninety-five percent of the prognostic data were obtained 5 years after PCI. The cumulative event-free survival rate was significantly lower in the high Lp(a) group (p = 0.02; log-rank test).

Conclusions: Lp(a) levels may be an alternative predictor of further plaque regression and the likelihood of major adverse cardiovascular events in statin-treated ACS patients.
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http://dx.doi.org/10.1016/j.jjcc.2020.01.005DOI Listing
July 2020

Progression of left anterior descending artery dissection due to stent implantation for spontaneous coronary artery dissection of left circumflex artery: a case report.

Eur Heart J Case Rep 2019 Dec 9;3(4):1-6. Epub 2019 Oct 9.

Université de Strasbourg, Pôle d'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, 1 place de l'Hôpital, 67091 Strasbourg, France.

Background: Spontaneous coronary artery dissection (SCAD) is a rare disease that predominantly affects woman. Percutaneous coronary intervention (PCI) is recommended only in patients with ongoing ischaemia because it carries a high risk of procedural complications in SCAD patients.

Case Summary: A 51-year-old woman was admitted to our institution owing to severe chest pain. Coronary angiography showed a diffuse narrowing and radiolucent luminal flap which runs parallel to the vessel wall in the proximal left circumflex coronary artery and SCAD was diagnosed. After PCI was undertaken, optical coherence tomography disclosed a circular haematoma at the stent distal segment and an intimal tear at the distal left main coronary artery. A conservative approach was decided owing to patient stability without evidence of ongoing ischaemia and normal coronary flow. Thirty minutes later, the patient started to complain of chest pain with the ST-segment elevation in leads I, aVL, and V2-3. Coronary angiography demonstrated a total occlusion of the second diagonal brunch and double lumen morphology at the proximal-potion of left anterior descending with TIMI2 distal flow suggesting the extension of coronary dissection. Optical coherence tomography imaging revealed that the entry door of the dissection was located where the small intimal tear was found. Percutaneous coronary intervention was successfully performed, and the patient was discharged without any complication.

Discussion: Although the underlying mechanism of recurrent SCAD remain largely unknown, our case suggests that the residual inlet of the dissection may associate with the extension of the coronary dissection.
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http://dx.doi.org/10.1093/ehjcr/ytz173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6939789PMC
December 2019

Atrial Fibrillation Progression Is Associated with Cell Senescence Burden as Determined by p53 and p16 Expression.

J Clin Med 2019 Dec 23;9(1). Epub 2019 Dec 23.

INSERM UMR 1260-Regenerative Nanomedecine, FMTS, Université de Strasbourg-Faculté de Pharmacie, 67401 Illkirch-Graffenstaden, France.

Background: Whilst the link between aging and thrombogenicity in atrial fibrillation (AF) is well established, the cellular underlying mechanisms are unknown. In AF, the role of senescence in tissue remodeling and prothrombotic state remains unclear.

Aims: We investigated the link between AF and senescence by comparing the expression of senescence markers (p53 and p16), with prothrombotic and inflammatory proteins in right atrial appendages from patients in AF and sinus rhythm (SR).

Methods: The right atrial appendages of 147 patients undergoing open-heart surgery were harvested. Twenty-one non-valvular AF patients, including paroxysmal (PAF) or permanent AF (PmAF), were matched with 21 SR patients according to CHA2DS2-VASc score and treatment. Protein expression was assessed by tissue lysates Western blot analysis.

Results: The expression of p53, p16, and tissue factor (TF) was significantly increased in AF compared to SR (0.91 ± 0.31 vs. 0.58 ± 0.31, = 0.001; 0.76 ± 0.32 vs. 0.35 ± 0.18, = 0.0001; 0.88 ± 0.32 vs. 0.68 ± 0.29, = 0.045, respectively). Expression of endothelial NO synthase (eNOS) was lower in AF (0.25 ± 0.15 vs. 0.35 ± 0.12, = 0.023). There was a stepwise increase of p53, p16, TF, matrix metalloproteinase-9, and an eNOS progressive decrease between SR, PAF, and PmAF. AF was the only predictive factor of p53 and p16 elevation in multivariate analysis. The study brought new evidence indicating that AF progression is strongly related to human atrial senescence burden and points at a link between senescence, thrombogenicity, endothelial dysfunction and atrial remodeling.
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http://dx.doi.org/10.3390/jcm9010036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019631PMC
December 2019