Publications by authors named "Franck Thuny"

131 Publications

Myocardial T1 and T2 Mapping by Magnetic Resonance in Patients With Immune Checkpoint Inhibitor-Associated Myocarditis.

J Am Coll Cardiol 2021 Mar;77(12):1503-1516

Cardio-Oncology Program, Department of Cardiology, Clínica Universidad de Navarra, Pamplona and Madrid, Spain.

Background: Myocarditis is a potentially fatal complication of immune checkpoint inhibitor (ICI) therapy. Data on the utility of cardiovascular magnetic resonance (CMR) T1 and T2 mapping in ICI myocarditis are limited.

Objectives: This study sought to assess the value of CMR T1 and T2 mapping in patients with ICI myocarditis.

Methods: In this retrospective study from an international registry of patients with ICI myocarditis, clinical and CMR findings (including T1 and T2 maps) were collected. Abnormal T1 and T2 were defined as 2 SD above site (vendor/field strength specific) reference values and a z-score was calculated for each patient. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block.

Results: Of 136 patients with ICI myocarditis with a CMR, 86 (63%) had T1 maps and 79 (58%) also had T2 maps. Among the 86 patients (66.3 ± 13.1 years of age), 36 (41.9%) had a left ventricular ejection fraction <55%. Across all patients, mean z-scores for T1 and T2 values were 2.9 ± 1.9 (p < 0.001) and 2.2 ± 2.1 (p < 0.001), respectively. On Siemens 1.5-T scanner (n = 67), native T1 (1,079.0 ± 55.5 ms vs. 1,000.3 ± 22.1 ms; p < 0.001) and T2 (56.2 ± 4.9 ms vs. 49.8 ± 2.2 ms; p < 0.001) values were elevated compared with reference values. Abnormal T1 and T2 values were seen in 78% and 43% of the patients, respectively. Applying the modified Lake Louise Criteria, 95% met the nonischemic myocardial injury criteria and 53% met the myocardial edema criteria. Native T1 values had excellent discriminatory value for subsequent MACE, with an area under the curve of 0.91 (95% confidence interval: 0.84 to 0.98). Native T1 values (for every 1-unit increase in z-score, hazard ratio: 1.44; 95% confidence interval: 1.12 to 1.84; p = 0.004) but not T2 values were independently associated with subsequent MACE.

Conclusions: The use of T1 mapping and application of the modified Lake Louise Criteria provides important diagnostic value, and T1 mapping provides prognostic value in patients with ICI myocarditis.
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http://dx.doi.org/10.1016/j.jacc.2021.01.050DOI Listing
March 2021

Electrocardiographic features of immune checkpoint inhibitor associated myocarditis.

J Immunother Cancer 2021 Mar;9(3)

Department of Dermatology and Allergy, LMU Klinikum, Munich, Germany.

Background: Myocarditis is a highly morbid complication of immune checkpoint inhibitor (ICI) use that remains inadequately characterized. The QRS duration and the QTc interval are standardized electrocardiographic measures that are prolonged in other cardiac conditions; however, there are no data on their utility in ICI myocarditis.

Methods: From an international registry, ECG parameters were compared between 140 myocarditis cases and 179 controls across multiple time points (pre-ICI, on ICI prior to myocarditis, and at the time of myocarditis). The association between ECG values and major adverse cardiac events (MACE) was also tested.

Results: Both the QRS duration and QTc interval were similar between cases and controls prior to myocarditis. When compared with controls on an ICI (93±19 ms) or to baseline prior to myocarditis (97±19 ms), the QRS duration prolonged with myocarditis (110±22 ms, p<0.001 and p=0.009, respectively). In contrast, the QTc interval at the time of myocarditis (435±39 ms) was not increased compared with pre-myocarditis baseline (422±27 ms, p=0.42). A prolonged QRS duration conferred an increased risk of subsequent MACE (HR 3.28, 95% CI 1.98 to 5.62, p<0.001). After adjustment, each 10 ms increase in the QRS duration conferred a 1.3-fold increase in the odds of MACE (95% CI 1.07 to 1.61, p=0.011). Conversely, there was no association between the QTc interval and MACE among men (HR 1.33, 95% CI 0.70 to 2.53, p=0.38) or women (HR 1.48, 95% CI 0.61 to 3.58, p=0.39).

Conclusions: The QRS duration is increased in ICI myocarditis and is associated with increased MACE risk. Use of this widely available ECG parameter may aid in ICI myocarditis diagnosis and risk-stratification.
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http://dx.doi.org/10.1136/jitc-2020-002007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929895PMC
March 2021

Intensified immunosuppressive therapy in patients with immune checkpoint inhibitor-induced myocarditis.

J Immunother Cancer 2020 12;8(2)

University Mediterranean Centre of Cardio-Oncology (MEDI-CO centre), Unit of Heart Failure and Valvular Heart Diseases, Department of Cardiology, Nord Hospital, Centre for CardioVascular and Nutrition research (C2VN), INSERM 1263, INRAE 1260, Aix-Marseille University, Assistance Publique - Hôpitaux de Marseille, Marseille, Provence-Alpes-Côte d'Azur, France

Background: Myocarditis is a rare but life-threatening adverse event of cancer treatments with immune checkpoint inhibitors (ICIs). Recent guidelines recommend the use of high doses of corticosteroids as a first-line treatment, followed by intensified immunosuppressive therapy (IIST) in the case of unfavorable evolution. However, this strategy is empirical, and no studies have specifically addressed this issue. Therefore, we aimed to investigate and compare the clinical course, management and outcome of ICI-induced myocarditis patients requiring or not requiring IIST.

Methods: This case-control study included all patients consecutively admitted to The Mediterranean University Center of Cardio-Oncology (Aix-Marseille University, France) for the diagnosis of ICI-induced myocarditis according to Bonaca's criteria and treated with or without IIST. In addition, we searched PubMed and included patients from previously published case reports treated with IIST in the analysis. The clinical, biological, imaging, treatment, all-cause death and cardiovascular death data of patients who required IIST were compared with those of patients who did not.

Results: A total of 60 patients (69±12 years) were included (36 were treated with IIST and 24 were not). Patients requiring IIST were more likely to have received a combination of ICIs (39% vs 8%, p=0.01), and developed the first symptoms/signs of myocarditis earlier after the onset of ICI therapy (median, 18 days vs 60 days, p=0.002). They had a significantly higher prevalence of sustained ventricular arrhythmia, complete atrioventricular block, cardiogenic shock and troponin elevation. Moreover, they were more likely to have other immune-related adverse events simultaneously (p<0.0001), especially myositis (p=0.0002) and myasthenia gravis (p=0.009). Patients who required IIST were more likely to die from any cause (50% vs 21%, p=0.02). Among them, patients who received infliximab were more likely to die from cardiovascular causes (OR, 12.0; 95% CI 2.1 to 67.1; p=0.005).

Conclusion: The need for IIST was more common in patients who developed myocarditis very early after the start of ICI therapy, as well as when hemodynamic/electrical instability or neuromuscular adverse events occurred. Treatment with infliximab might be associated with an increased risk of cardiovascular death.
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http://dx.doi.org/10.1136/jitc-2020-001887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725077PMC
December 2020

Perspectives on the COVID-19 pandemic impact on cardio-oncology: results from the COVID-19 International Collaborative Network survey.

Cardiooncology 2020 Nov 27;6(1):28. Epub 2020 Nov 27.

Franciscan Health, Indianapolis, IN, USA.

Background: Re-allocation of resources during the COVID-19 pandemic has resulted in delays in care delivery to patients with cardiovascular disease and cancer. The ability of health care providers to provide optimal care in this setting has not been formally evaluated.

Objectives: To assess the impact of COVID-19 resource re-allocation on scheduling, testing, elective procedures, telemedicine access, use of new COVID-19 therapies, and providers' opinions on healthcare policies among oncology and cardiology practitioners.

Methods: An electronic survey was conducted by a cardio-oncology collaborative network through regional and state chapters of the American College of Cardiology, American Society of Clinical Oncology, and the International Cardio-Oncology Society. Descriptive statistics were reported by frequency and proportion for analyses, and stratified categorically by geographic region and specialty.

Results: One thousand four hundred fifteen providers (43 countries) participated: 986 cardiologists, 306 oncologists, and 118 trainees/internal medicine. 63% (195/306) of oncologists vs 92% (896/976) of cardiologists reported cancellations of treatments/elective procedures (p = 0.01). 46% (442/970) of cardiologists and 25% (76/303) of oncologists modified the scope of their practice (p = < 0.001). Academic physicians (74.5%) felt better supplied with personal protective equipment (PPE) vs non-academic (74.5% vs 67.2%; p = 0.018). Telemedicine was less common in Europe 81% (74/91), and Latin America 64% (101/158), than the United States, 88% (950/1097) (p = < 0.001). 95% of all groups supported more active leadership from medical professional societies.

Conclusions: These results support initiatives to promote expanded coverage for telemedicine, increased access to PPE, better testing availability and involvement of medical professional societies to help with preparedness for future health care crisis.
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http://dx.doi.org/10.1186/s40959-020-00085-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691954PMC
November 2020

Cardiovascular Toxicity Related to Cancer Treatment: A Pragmatic Approach to the American and European Cardio-Oncology Guidelines.

J Am Heart Assoc 2020 09 5;9(18):e018403. Epub 2020 Sep 5.

Unit of Heart Failure and Valvular Heart Diseases Department of Cardiology Nord Hospital Center for CardioVascular and Nutrition Research (C2VN) University Mediterranean Center of Cardio-Oncology (MEDI-CO Center) Assistance Publique - Hôpitaux de MarseilleAix-Marseille University Marseille France.

The considerable progress made in the field of cancer treatment has led to a dramatic improvement in the prognosis of patients with cancer. However, toxicities resulting from these treatments represent a cost that can be harmful to short- and long-term outcomes. Adverse events affecting the cardiovascular system are one of the greatest challenges in the overall management of patients with cancer, as they can compromise the success of the optimal treatment against the tumor. Such adverse events are associated not only with older chemotherapy drugs such as anthracyclines but also with many targeted therapies and immunotherapies. Recognizing this concern, several American and European governing societies in oncology and cardiology have published guidelines on the cardiovascular monitoring of patients receiving potentially cardiotoxic cancer therapies, as well as on the management of cardiovascular toxicities. However, the low level of evidence supporting these guidelines has led to numerous discrepancies, leaving clinicians without a consensus strategy to apply. A cardio-oncology expert panel from the French Working Group of Cardio-Oncology has undertaken an ambitious effort to analyze and harmonize the most recent American and European guidelines to propose roadmaps and decision algorithms that would be easy for clinicians to use in their daily practice. In this statement, the experts addressed the cardiovascular monitoring strategies for the cancer drugs associated with the highest risk of cardiovascular toxicities, as well as the management of such toxicities.
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http://dx.doi.org/10.1161/JAHA.120.018403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727003PMC
September 2020

Identification of anticancer drugs associated with atrial fibrillation - analysis of the WHO pharmacovigilance database.

Eur Heart J Cardiovasc Pharmacother 2020 Apr 30. Epub 2020 Apr 30.

Normandie Univ, UNICAEN, CHU de Caen Normandie, PICARO Cardio-oncology Program, Department of Pharmacology, EA 4650, Signalisation, électrophysiologie et imagerie des lésions d'ischémie-reperfusion myocardique, F-14000 CAEN, France.

Aims: The explosion of novel anticancer therapies has meant emergence of cardiotoxicity signals including atrial fibrillation (AF). Reliable data concerning the liability of anticancer drugs in inducing AF are scarce. Using the World Health Organization individual case safety report database, VigiBase®, we aimed to determine the association between anticancer drugs and AF.

Methods And Results: A disproportionality analysis evaluating the multivariable adjusted reporting odd-ratios (aROR) for AF with their 99.97% confidence intervals (CI) was performed for 176 FDA- or EMA-labeled anticancer drugs in VigiBase®, followed by a descriptive analysis of AF cases for the anticancer drugs identified in VigiBase®. ClinicalTrial registration number: NCT03530215.A total of 11,757 AF cases associated with at least one anticancer drug were identified in VigiBase® of which 95.8% were deemed serious. Nineteen anticancer drugs were significantly associated with AF of which 14 (74%) are used in hematologic malignancies and 9 (45%) represented new AF associations not previously confirmed in literature including immunomodulating agents (lenalidomide, pomalidomide), several kinase inhibitors (nilotinib, ponatinib, midostaurin), antimetabolites (azacytidine, clofarabine), docetaxel (taxane) and obinutuzumab, an anti-CD20 monoclonal antibody.

Conclusion: Although cancer malignancy itself may generate AF, we identified 19 anticancer drugs significantly associated with a significant increase in AF over-reporting. This pharmacovigilance study provides evidence that anticancer drugs themselves could represent independent risk factors for AF development. Dedicated prospective clinical trials are now required to confirm these 19 associations. This list of suspected anticancer drugs should be known by physicians when confronted to AF in cancer patients, particularly in case of hematologic malignancies.
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http://dx.doi.org/10.1093/ehjcvp/pvaa037DOI Listing
April 2020

Immune Checkpoint Inhibitor Rechallenge After Immune-Related Adverse Events in Patients With Cancer.

JAMA Oncol 2020 06;6(6):865-871

Normandie University, University of Caen Normandy, Centre Hospitalier Universitaire (CHU) de Caen Normandie, PICARO Cardio-oncology Program, Department of Pharmacology, EA 4650, Signalisation, Électrophysiologie et Imagerie des Lésions d'Ischémie-Reperfusion Myocardique, Caen, France.

Importance: Limited information is available on the safety of a rechallenge with an immune checkpoint inhibitor (ICI) after an immune-related adverse event (irAE).

Objective: To identify the recurrence rate of the same irAE that prompted discontinuation of ICI therapy after an ICI rechallenge in patients with cancer and to identify the clinical features associated with such recurrences.

Design, Setting, And Participants: This observational, cross-sectional, pharmacovigilance cohort study examined individual case safety reports from the World Health Organization database VigiBase, which contains case reports from more than 130 countries. Case reports were extracted from database inception (1967) to September 1, 2019. All consecutive ICI cases with at least 1 associated irAE were included.

Main Outcomes And Measures: The primary outcome was the rate of recurrence of the initial irAE after an ICI rechallenge. Secondary outcomes included the factors associated with the recurrence after a rechallenge among informative rechallenges, the recurrence rate according to the ICI regimen (anti-programmed cell death 1 or anti-programmed cell death ligand 1 monotherapy, anti-cytotoxic T-lymphocyte antigen-4 monotherapy, or combination therapy), and the rate of occurrence of a different irAE after a rechallenge.

Results: A total of 24 079 irAE cases associated with at least 1 ICI were identified. Among the irAEs, 452 of 6123 irAEs associated with ICI rechallenges (7.4%) were informative rechallenges. One hundred thirty recurrences (28.8%; 95% CI, 24.8-33.1) of the initial irAE were observed. In a rechallenge, colitis (reporting odds ratio [OR], 1.77; 95% CI, 1.14-2.75; P = .01), hepatitis (reporting OR, 3.38; 95% CI, 1.31-8.74; P = .01), and pneumonitis (reporting OR, 2.26; 95% CI, 1.18-4.32; P = .01) were associated with a higher recurrence rate, whereas adrenal events were associated with a lower recurrence rate (reporting OR, 0.33; 95% CI, 0.13-0.86; P = .03) compared with other irAEs.

Conclusions And Relevance: This cohort study found a 28.8% recurrence rate of the same irAE associated with the discontinuation of ICI therapy after a rechallenge with the same ICI. Resuming ICI therapy could be considered for select patients, with appropriate monitoring and use of standard treatment algorithms to identify and treat toxic effects.
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http://dx.doi.org/10.1001/jamaoncol.2020.0726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163782PMC
June 2020

[Valvular heart disease].

Rev Prat 2019 Nov;69(9):e291-e305

Unité Nord insuffisance cardiaque et valvulopathies, Aix-Marseille Université, Assistance publique-Hôpitaux de Marseille, hôpital Nord, 13015 Marseille, France.

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November 2019

Acute Coronary Syndrome With Immune Checkpoint Inhibitors: A Proof-of-Concept Case and Pharmacovigilance Analysis of a Life-Threatening Adverse Event.

Can J Cardiol 2020 04 11;36(4):476-481. Epub 2019 Dec 11.

University Mediterranean Centre of Cardio-Oncology, Assistance Publique-Hôpitaux de Marseille, Aix-Marseille University, and Unit of Heart Failure and Valvular Heart Diseases, Department of Cardiology, Hôpital Nord, Marseille, France; Groupe Méditerranéen de Cardio-Oncologie, Marseille, France; Centre for Cardiovascular and Nutrition Research, Aix-Marseille University, INSERM 1263, INRA 1260, Marseille, France. Electronic address:

Isolated cases of acute coronary syndrome (ACS) associated with immune checkpoint inhibitors (ICIs) have been described without the establishment of a formal cause-and-effect relationship between treatment and adverse event. We reported a case of ACS after the first administration of an ICI and with a fatal recurrence in another coronary area immediately after readministration. According to guidelines, causality was considered to be certain. Subsequently, we queried the French pharmacovigilance database and found 4 cases of ACS with coronary artery thrombosis. Causality was probable in those patients. These data suggest that ACS may be another life-threatening cardiac adverse event occurring with ICI exposure.
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http://dx.doi.org/10.1016/j.cjca.2019.11.035DOI Listing
April 2020

Cardiovascular magnetic resonance in immune checkpoint inhibitor-associated myocarditis.

Eur Heart J 2020 05;41(18):1733-1743

Division of Oncology and Hematology, Department of Medicine, Lehigh Valley Hospital, 1200 S Cedar Crest Blvd, Allentown, PA 18103, USA.

Aims: Myocarditis is a potentially fatal complication of immune checkpoint inhibitors (ICI). Sparse data exist on the use of cardiovascular magnetic resonance (CMR) in ICI-associated myocarditis. In this study, the CMR characteristics and the association between CMR features and cardiovascular events among patients with ICI-associated myocarditis are presented.

Methods And Results: From an international registry of patients with ICI-associated myocarditis, clinical, CMR, and histopathological findings were collected. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. In 103 patients diagnosed with ICI-associated myocarditis who had a CMR, the mean left ventricular ejection fraction (LVEF) was 50%, and 61% of patients had an LVEF ≥50%. Late gadolinium enhancement (LGE) was present in 48% overall, 55% of the reduced EF, and 43% of the preserved EF cohort. Elevated T2-weighted short tau inversion recovery (STIR) was present in 28% overall, 30% of the reduced EF, and 26% of the preserved EF cohort. The presence of LGE increased from 21.6%, when CMR was performed within 4 days of admission to 72.0% when CMR was performed on Day 4 of admission or later. Fifty-six patients had cardiac pathology. Late gadolinium enhancement was present in 35% of patients with pathological fibrosis and elevated T2-weighted STIR signal was present in 26% with a lymphocytic infiltration. Forty-one patients (40%) had MACE over a follow-up time of 5 months. The presence of LGE, LGE pattern, or elevated T2-weighted STIR were not associated with MACE.

Conclusion: These data suggest caution in reliance on LGE or a qualitative T2-STIR-only approach for the exclusion of ICI-associated myocarditis.
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http://dx.doi.org/10.1093/eurheartj/ehaa051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205467PMC
May 2020

Global Longitudinal Strain and Cardiac Events in Patients With Immune Checkpoint Inhibitor-Related Myocarditis.

J Am Coll Cardiol 2020 02;75(5):467-478

Cardiology Division, New York-Presbyterian Hospital, Weill Cornell Medical Center, New York, New York.

Background: There is a need for improved methods for detection and risk stratification of myocarditis associated with immune checkpoint inhibitors (ICIs). Global longitudinal strain (GLS) is a sensitive marker of cardiac toxicity among patients receiving standard chemotherapy. There are no data on the use of GLS in ICI myocarditis.

Objectives: This study sought to evaluate the role of GLS and assess its association with cardiac events among patients with ICI myocarditis.

Methods: This study retrospectively compared echocardiographic GLS by speckle tracking at presentation with ICI myocarditis (cases, n = 101) to that from patients receiving an ICI who did not develop myocarditis (control subjects, n = 92). Where available, GLS was also measured pre-ICI in both groups. Major adverse cardiac events (MACE) were defined as a composite of cardiogenic shock, arrest, complete heart block, and cardiac death.

Results: Cases and control subjects were similar in age, sex, and cancer type. At presentation with myocarditis, 61 cases (60%) had a normal ejection fraction (EF). Pre-ICI, GLS was similar between cases and control subjects (20.3 ± 2.6% vs. 20.6 ± 2.0%; p = 0.60). There was no change in GLS among control subjects on an ICI without myocarditis (pre-ICI vs. on ICI, 20.6 ± 2.0% vs. 20.5 ± 1.9%; p = 0.41); in contrast, among cases, GLS decreased to 14.1 ± 2.8% (p < 0.001). The GLS at presentation with myocarditis was lower among cases presenting with either a reduced (12.3 ± 2.7%) or preserved EF (15.3 ± 2.0%; p < 0.001). Over a median follow-up of 162 days, 51 (51%) experienced MACE. The risk of MACE was higher with a lower GLS among patients with either a reduced or preserved EF. After adjustment for EF, each percent reduction in GLS was associated with a 1.5-fold increase in MACE among patients with a reduced EF (hazard ratio: 1.5; 95% confidence interval: 1.2 to 1.8) and a 4.4-fold increase with a preserved EF (hazard ratio: 4.4; 95% confidence interval: 2.4 to 7.8).

Conclusions: GLS decreases with ICI myocarditis and, compared with control subjects, was lower among cases presenting with either a preserved or reduced EF. Lower GLS was strongly associated with MACE in ICI myocarditis presenting with either a preserved or reduced EF.
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http://dx.doi.org/10.1016/j.jacc.2019.11.049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067226PMC
February 2020

Late cardiac adverse events in patients with cancer treated with immune checkpoint inhibitors.

J Immunother Cancer 2020 01;8(1)

CHU de Caen, PICARO Cardio-oncology Program, Department of Pharmacology, CHU de Caen, Caen, France.

Background: Immune checkpoint inhibitor (ICI)-associated early cardiac adverse events (CAEs), mostly acute and fulminant myocarditis, have been well characterized and mainly occur during the first 90 days after ICI therapy initiation. ICI-associated late CAEs (occurring after the first 90 days of treatment) have not yet been described.

Methods: First, we compared characteristics of a cohort involving early (defined as a CAE time to onset (TTO) of <90 days after ICI therapy initiation) and late (defined as a CAE TTO of ≥90 days after ICI therapy initiation) ICI-associated CAE consecutive cases who were referred to three French cardio-oncology units. Second, ICI-associated CAE cases were searched in VigiBase, the WHO global individual case safety report database, and early and late ICI-associated CAEs were compared.

Results: In the cohort study, compared with early CAE cases (n=19, median TTO of 14 days), late ICI-associated CAE cases (n=19, median TTO of 304 days) exhibited significantly more left ventricular systolic dysfunction (LVSD) and heart failure (HF) and less frequent supraventricular arrhythmias. In VigiBase, compared with early cases (n=437, 73.3%, median TTO 21 days), the late ICI-associated CAE reports (n=159, 26.7%, median TTO 178 days) had significantly more frequent HF (21.1% vs 31.4%, respectively, p=0.01). Early and late ICI-associated CAE cases had similarly high mortality rates (40.0% vs 44.4% in the cohort and 30.0% vs 27.0% in VigiBase, respectively).

Conclusions: Late CAEs could occur with ICI therapy and were mainly revealed to be HF with LVSD.

Trial Registration Numbers: NCT03678337, NCT03882580, and NCT03492528.
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http://dx.doi.org/10.1136/jitc-2019-000261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057417PMC
January 2020

[Myocarditis: Uncommon but severe toxicity of immune checkpoint inhibitors].

Bull Cancer 2019 Nov 15;106(11):1050-1056. Epub 2019 Oct 15.

Hôpital de la Croix-Rousse et Hôpital Lyon Sud, hospices civils de Lyon, Cardiology Department, 69004, Lyon, France; Université de Lyon, université Claude-Bernard Lyon 1, hospices civils de Lyon, CREATIS ; CNRS UMR5220, INSA-Lyon, IMMUCARE, Inserm U1044, 69004, Lyon, France.

Traditional cancer therapies, such as treatment with anthracyclines and chest radiation, are known to induce cardiovascular complications. Currently, the increase of cancer therapies will involve new mechanisms such as cancer immunotherapies, also called immune checkpoint inhibitors (PD-1, PD-L1 and CTLA-4 inhibitors). These treatments have shown long-term remissions in subgroup of cancers, including melanomas, non-small-cell lung cancer, urothelial carcinoma, renal cell carcinoma, squamous cell carcinoma of the head and neck and colorectal cancer. Although these treatments will change the natural course of these cancers, they may sometimes induce cardiovascular complications, which has been reported as about 1 % in the literature. Currently, the physicians must keep in mind one uncommon but severe cardiac complication: auto-immune myocarditis. The clinical presentation may include various symptoms like chest pain, heart failure or rhythm disorders. In this situation, a baseline cardiologic check-up before starting cancer immunotherapy may be very helpful. Cardiac biomarkers (troponin and brain natriuretic peptide) and 12-lead resting electrocardiogram must be promptly performed when myocarditis is suspected. A cardiologist's opinion must be requested in emergency to discuss both a transthoracic echocardiography and the appropriate treatment (stopping immunotherapy, adding immunosuppressive treatment such as corticoids) and the monitoring in an intensive care unit. Cardiac MRI and endomyocardial biopsies may help to approach the final diagnosis. In this situation, other cancer therapies may be discussed.
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http://dx.doi.org/10.1016/j.bulcan.2019.09.003DOI Listing
November 2019

Cardio-oncology: Clinical and imaging perspectives for optimal cardiodetection and cardioprotection in patients with cancer.

Arch Cardiovasc Dis 2019 Oct 12;112(10):550-558. Epub 2019 Sep 12.

Inserm 856, université Pierre et Marie Curie (Paris VI), hôpitaux universitaires Est Parisien (Hôpital Saint Antoine, Hôpital Tenon), AP-HP, 75571 Paris, France; Cardio-oncology Programme AP-HP, 75013 Paris, France.

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http://dx.doi.org/10.1016/j.acvd.2019.07.001DOI Listing
October 2019

Pulmonary hypertension in patients with myeloproliferative neoplasms: A large cohort of 183 patients.

Eur J Intern Med 2019 Oct 14;68:71-75. Epub 2019 Aug 14.

Hematology and Cellular Therapy Department, La Conception, University Hospital of Marseille, France; Aix-Marseille University, INSERM, UMR1090 TAGC, Marseille F_13288, France.

Background: Chronic myeloproliferative neoplasms (MPN) are recognized as a cause of pulmonary hypertension (pH). We ought to describe the prevalence and characteristics of PH in a cohort of MPN who were screened using transthoracic echocardiography (TTE).

Methods: One hundred eighty-three newly diagnosed consecutive MPN patients were prospectively evaluated using TTE to detect PH.

Results: Two patients were diagnosed with chronic eosinophilic leukemia, two patients had post-essential thrombocythemia (ET) myelofibrosis (MF), two patients had post-polycythemia vera (PV) MF, 11 patients had primary myelofibrosis (PMF), 28 patients had chronic myeloid leukemia (CML), 51 patients had PV, and 87 patients had ET. TTE was used to determine PH, and PH was suspected in 16 of 183 patients as follows: four with PV, seven with ET, two with PMF, and three with CML. Two patients with ET were excluded because of global cardiac failure. Three patients underwent right heart catheterization to confirm PH. The 14 (7.7%) patients with PH had no cardiac or lung disease that directly involved MPN in PH development.

Conclusion: In this large cohort of 183 MPN patients, TTE was used to diagnose PH, and 14 patients (7.7%) developed PH. This prevalence was lower than expected based on previously reported data, but it remains higher than in the general population.
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http://dx.doi.org/10.1016/j.ejim.2019.08.004DOI Listing
October 2019

Takotsubo syndrome in patients with cancer treated with immune checkpoint inhibitors: a new adverse cardiac complication.

Eur J Heart Fail 2019 Jul;21(7):945-947

Assistance Publique-Hôpitaux de Paris, Hôpital Saint Antoine, Department of Cardiology, Paris, France; INSERM U 856, Paris, France and UNICO APHP.6 Cardio-oncology Program.

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http://dx.doi.org/10.1002/ejhf.1497DOI Listing
July 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

High incidence of atrial fibrillation in patients treated with ibrutinib.

Open Heart 2019;6(1):e001049. Epub 2019 May 8.

Department of Cardiology, Unit of Heart Failure and Valvular Heart Diseases, Mediterranean University Cardio-Oncology Center (MEDI-CO Center), Hôpital Nord, Aix-Marseille I University, Marseille, France.

Objective: Atrial fibrillation (AF) is one of the most common side effects of ibrutinib, a drug that has dramatically improved the prognosis of chronic B-cell malignancies such as chronic lymphocytic leukaemia (CLL). The true incidence of ibrutinib-related AF (IRAF) is not well known and its therapeutic management poses unique challenges especially due to the inherent risk of bleeding. We aimed to determine the incidence and predictors of IRAF, and to analyse its management and outcome.

Methods: A standardised monitoring was applied at two cardio-oncology clinics in consecutive patients referred before and during ibrutinib therapy. The primary endpoint was the incidence of IRAF. The excess of AF incidence with ibrutinib was studied by comparing the incidence of IRAF with the expected incidence of AF in general population and in patients with CLL not exposed to ibrutinib.

Results: 53 patients were included. The incidence of IRAF was 38% at 2 years and the risk was 15-fold higher than the AF risk in both the general population and patients with CLL not exposed to ibrutinib (p<0.0001). The majority of cases occurred in asymptomatic patients within the first 6 months. Left atrial volume index ≥40 mL/m at treatment initiation identified patients at high risk of developing IRAF. No major bleeding events occurred in patients on ibrutinib, although the majority of patients with IRAF were treated with anticoagulants.

Conclusions: This cardio-oncology study showed that the risk of IRAF was much higher than previously reported. The majority of cases occurred in asymptomatic patients justifying close monitoring.
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http://dx.doi.org/10.1136/openhrt-2019-001049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519413PMC
May 2019

Dynamic iron status after acute heart failure.

Arch Cardiovasc Dis 2019 Jun - Jul;112(6-7):410-419. Epub 2019 Apr 18.

Heart Failure and Valvular Heart Disease Unit, Mediterranean University Cardio-Oncology (MEDI-CO) Centre, Department of Cardiology, Aix-Marseille University, hôpital Nord, AP-HM, chemin des Bourrely, 13015 Marseille, France; Inserm 1263, INRA, centre de recherche cardiovasculaire et nutrition (C2VN), Aix-Marseille University, 13385 Marseille, France. Electronic address:

Background: Iron deficiency (ID) is common in heart failure (HF), and is associated with unfavourable clinical outcomes. Although it is recommended to screen for ID in HF, there is no clear consensus on the optimal timing of its assessment.

Aim: To analyse changes in iron status during a short-term follow-up in patients admitted for acute HF.

Methods: Iron status (serum ferritin concentration and transferrin saturation) was determined in 110 consecutive patients (median age: 81 years) admitted to a referral centre for acute HF, at three timepoints (admission, discharge and 1 month after discharge). ID was defined according to the guidelines.

Results: The prevalence rates of ID at admission, discharge and 1 month were, respectively, 75% (95% confidence interval [CI] 67-83%), 61% (95% CI: 52-70%), and 70% (95% CI: 61-79%) (P=0.008). Changes in prevalence were significant between admission and discharge (P=0.0018). Despite a similar ID prevalence at admission and 1 month (P=0.34), iron status changed in 25% of patients. Between admission and discharge, variation in C-reactive protein correlated significantly with that of ferritin (ρ=0.30; P=0.001). Advanced age, anaemia, low ferritin concentration and low creatinine clearance were associated with the persistence of ID from admission to 1 month.

Conclusions: Iron status is dynamic in patients admitted for acute HF. Although ID was as frequent at admission as at 1 month after discharge, iron status varied in 25% of patients.
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http://dx.doi.org/10.1016/j.acvd.2019.02.002DOI Listing
December 2019

[How to organise cardiovascular management of cancer patients?]

Rev Prat 2018 Mar;68(3):332-335

Aix-Marseille université, Assistance publique-Hôpitaux de Marseille, unité Nord insuffisance cardiaque et valvulopathies, centre méditerranéen hospitalo-universitaire de cardiologie oncologique - Medi-CO Center, hôpital Nord, Marseille, France.

How to organise cardiovascular management of cancer patients? Advances in cancer therapy have reduced cancer mortality. However, these results are sometimes achieved at the cost of cardiovascular adverse events that may limit the overall benefit of treatment. Cardio-oncology is a recent discipline that aims to prevent, screen and manage cardiovascular diseases associated with or secondary to cancer treatment without compromising its effectiveness. These goals must therefore be integrated into the patient care program at the time of cancer diagnosis. Therefore, a cardiovascular toxicity risk assessment should be conducted prior treatment to identify patients candidate for closer monitoring. In parallel with their oncologic follow-up, these high-risk patients should receive cardiovascular follow-up that should not be restricted to a solely measurement of the left ventricular ejection fraction. Indeed, toxicities can be multiple, so the assessment must be comprehensive and should include at least clinical examination, ECG, cardiac imaging, and sometimes biomarkers. In the case of cardiovascular events, this organisation will enable an earlier and coordinated management with oncologists, which will result in an improvement of the patients' overall prognosis.
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March 2018

Influenza vaccination and myocarditis among patients receiving immune checkpoint inhibitors.

J Immunother Cancer 2019 02 22;7(1):53. Epub 2019 Feb 22.

Cardio-Oncology Program, Division of Cardiology, Hopitaux Universitaires est Paris, Paris, France.

Background: Influenza vaccination (FV) is recommended for patients with cancer. Recent data suggested that the administration of the FV was associated with an increase in immune-related adverse events (irAEs) among patients on immune checkpoint inhibitors (ICIs). Myocarditis is an uncommon but serious complication of ICIs and may also result from infection with influenza. There are no data testing the relationship between FV and the development of myocarditis on ICIs.

Methods: Patients on ICIs who developed myocarditis (n = 101) (cases) were compared to ICI-treated patients (n = 201) without myocarditis (controls). A patient was defined as having the FV if they were administered the FV from 6 months prior to start of ICI to anytime during ICI therapy. Alternate thresholds for FV status were also tested. The primary comparison of interest was the rate of FV between cases and controls. Patients with myocarditis were followed for major adverse cardiac events (MACE), defined as the composite of cardiogenic shock, cardiac arrest, hemodynamically significant complete heart block and cardiovascular death.

Results: The FV was administered to 25% of the myocarditis cases compared to 40% of the non-myocarditis ICI-treated controls (p = 0.01). Similar findings of lower rates of FV administration were noted among myocarditis cases when alternate thresholds were tested. Among the myocarditis cases, those who were vaccinated had 3-fold lower troponin levels when compared to unvaccinated cases (FV vs. No FV: 0.12 [0.02, 0.47] vs. 0.40 [0.11, 1.26] ng/ml, p = 0.02). Within myocarditis cases, those administered the FV also had a lower rate of other irAEs when compared to unvaccinated cases (36 vs. 55% p = 0.10) including lower rates of pneumonitis (12 vs. 36%, p = 0.03). During follow-up (175 [IQR 89, 363] days), 47% of myocarditis cases experienced a MACE. Myocarditis cases who received the FV were at a lower risk of cumulative MACE when compared to unvaccinated cases (24 vs. 59%, p = 0.002).

Conclusion: The rate of FV among ICI-related myocarditis cases was lower than controls on ICIs who did not develop myocarditis. In those who developed myocarditis related to an ICI, there was less myocardial injury and a lower risk of MACE among those who were administered the FV.
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http://dx.doi.org/10.1186/s40425-019-0535-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387531PMC
February 2019

OCT Analysis of Very Early Strut Coverage of the Synergy Stent in Non-ST Segment Elevation Acute Coronary Syndrome Patients.

J Invasive Cardiol 2019 01 11;31(1):10-14. Epub 2018 Nov 11.

Service de Cardiologie, Hôpital Nord Chemin des Bourrely, 13015, Marseille, France.

Objectives: Early endothelialization of drug-eluting stent (DES) is a major challenge to reduce the risk of stent thrombosis and the duration of dual-antiplatelet therapy (DAPT) in high bleeding-risk patients. The aim of the present study is to evaluate very early strut coverage with optical coherence tomography (OCT) of the Synergy stent (Boston Scientific) at 1 month in non-ST segment elevation acute coronary syndrome (NSTE-ACS) patients.

Methods: This substudy of the EARLY trial prospectively included NSTE-ACS patients treated with the Synergy DES. OCT analysis of the Synergy stent was performed during a staged PCI of additional lesions at 1 month. The primary endpoint was the percentage of covered struts assessed with OCT at 1 month.

Results: Twenty-four patients were included, with a mean stent length of 35.9 ± 10.1 mm per patient. The rate of covered struts was 78.5% out of 3839 struts analyzed. Nineteen patients (79.2%) had at least 70% of their struts covered. The average neointimal thickness was 0.0508 ± 0.016 mm.

Conclusions: In NSTE-ACS patients undergoing culprit percutaneous coronary intervention with the Synergy stent, the rate of covered struts at 1 month was 78.5%. This rapid coverage is in line with the results of clinical trials demonstrating the safety of short-duration DAPT in selected patients who are at high bleeding risk and treated with new-generation DES options.
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January 2019

Seasonal variations in cardiac implantable electronic device infections.

Heart Vessels 2019 May 10;34(5):824-831. Epub 2018 Nov 10.

APHM, Unit of Arrhythmias, Department of Cardiology, Aix-Marseille Univ, Hôpital Timone, Marseille, France.

Infections of cardiac implantable electronic devices (CIEDs) have increased over the past decade. However, the impact of the climate on CIED infections is unknown. To determine whether there is a seasonal variation in CIED infections. In this single-center observational study, retrospective analysis of prospectively collected data was performed. Timone Hospital in Marseille (south-east France) is a tertiary care institution and the regional reference center for management of CIED infections. All consecutive patients with CIED extractions for infectious reasons were included over a 12-year period. We noted the mean temperature (°C), precipitation (mm) and the incidence of CIED infections over this period. Among 612 patients [mean (standard deviation) age, 72.4 (13.0) years; 74.0% male], 238 had endocarditis alone (38.9%), 249 had pocket infection alone (40.7%), and 125 had both (20.4%). We found bacterial documentation in 428 patients (70.0%), commensal in 245 (40.0%). The incidence of CIED infections was positively associated with high temperature (regression coefficient = 0.075; P = 0.01) and precipitation (regression coefficient = 0.022; P < 0.01). Seasonal variation was specific of pocket infections, whether they were associated with endocarditis or not. Subgroups with infection seasonality were: women, elderly people (> 75 years), late CIED infection and skin commensal bacterial infections. We found a seasonal variation in pocket infections, whether associated with endocarditis or not. Infections were associated with elevated temperatures and precipitation. Therefore, specific prevention strategy should be discussed in high-risk patients.
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http://dx.doi.org/10.1007/s00380-018-1292-4DOI Listing
May 2019

Device-Related Thrombus After Left Atrial Appendage Occlusion With the Amulet Device.

Heart Lung Circ 2019 Nov 27;28(11):1683-1688. Epub 2018 Sep 27.

Aix-Marseille University, Assistance Publique - Hôpitaux de Marseille (APHM), Department of Cardiology, Nord Hospital, Chemin des Bourrelly, 13915 Marseille, Cedex, France; MARS Cardio, Mediterranean Association for Research and Studies in Cardiology, Nord Hospital, Chemin des Bourrelly, 13915 Marseille, Cedex, France.

Background: Left atrial appendage occlusion (LAAO) is increasingly used for stroke prevention in patients with atrial fibrillation who are considered unsuitable for a lifelong oral anticoagulant regimen. Recently, a single-centre study reported device-related thrombus formation in 16.7% of patients treated with the second-generation Amulet device (St. Jude Medical, St. Paul, MN, USA), presenting a potential major safety concern. As "real-world" data on device-related thrombus formation following LAAO with the Amulet occluder are scarce, we aimed to evaluate this outcome in a retrospective registry.

Methods: Clinical and tranosesophageal echocardiography data after LAAO with the Amulet in consecutive patients from three centres were collated.

Results: Among 38 patients (mean age 75.8 years), mean (standard deviation) CHADS-VASc and HAS-BLED scores were 4.4 (1.2) and 3.4 (0.9), respectively. All patients underwent successful device placement without procedure-related adverse events. The antithrombotic regimen at discharge consisted of dual antiplatelet therapy (DAPT) in 27 patients (71.1%), single antiplatelet therapy in 10 patients (26.3%), and no antithrombotic therapy in one patient (2.6%). Device-related thrombus was observed in one patient (2.6%) despite DAPT regimen. The outcome of this patient was uncomplicated after adjustment of oral anticoagulant therapy. No patients presented with a thromboembolic event following LAAO during a mean (standard deviation) follow-up of 15 (5) months.

Conclusions: In this retrospective study, device-related thrombus formation with the second-generation Amulet device was rare and occurred at a rate similar to that of the previous device. Importantly, no patient experienced a device-related thromboembolic event during follow-up. Larger real-life studies are required to confirm the safety profile of this increasingly used device.
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http://dx.doi.org/10.1016/j.hlc.2018.08.022DOI Listing
November 2019

Meta-Analysis of Potent P2Y12-ADP Receptor Antagonist Therapy Compared to Clopidogrel Therapy in Acute Coronary Syndrome Patients with Chronic Kidney Disease.

Thromb Haemost 2018 Oct 20;118(10):1839-1846. Epub 2018 Sep 20.

Department of Public Health (BIOSTIC), Aix-Marseille University, Hôpital de la Timone, Marseille, France.

Background:  The clinical benefit of anti-platelet agents in patients with chronic kidney disease (CKD) is uncertain. In addition, the risk-benefit ratio of potent oral P2Y12-adenosine diphosphate (ADP) receptor antagonists (PPAs), namely, prasugrel and ticagrelor, compared with clopidogrel in CKD patients suffering from acute coronary syndrome (ACS) remains unknown.

Objective:  We performed a meta-analysis of all studies comparing the clinical outcomes of PPA and clopidogrel therapy in CKD patients suffering from ACS.

Methods:  We searched PubMed, the Cochrane library, Google Scholar, Clinical trial.org and the abstracts of international cardiology congresses from April 2000 to October 2017. Clinical studies comparing PPA with clopidogrel in ACS patients with CKD were selected. Our literature research identified five studies which were included in the meta-analysis. The primary endpoint was a composite of major adverse cardiovascular events (MACEs) at the latest follow-up available. Secondary endpoint included bleedings.

Results:  We included data from three sub-group analysis of randomized clinical trials and two prospective observational studies ( = 31,234). Overall, PPAs were associated with lower rates of major cardiovascular events, with a pooled hazard ratio (pHR) of 0.88 (95% confidence interval [CI]: 0.79-0.99;  = 0.03), without increased bleedings (pHR = 1.10) (95% CI: 0.95-1.27;  = 0.18). In a sensitivity analysis restricted to studies enrolling invasively managed patients, the benefit of PPA on MACE was maintained (pHR = 0.85) (95% CI: 0.77-0.93;  < 0.001), including a reduction in mortality (pHR = 0.82) (95% CI: 0.7-0.96;  = 0.016).

Conclusion:  Compared with clopidogrel, PPAs were associated with a reduced rate of MACE without increased bleedings in CKD patients with ACS. Among invasively managed patients, this benefit from PPA included a reduction in mortality.
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http://dx.doi.org/10.1055/s-0038-1669426DOI Listing
October 2018

Doppler echocardiography for assessment of systemic vascular resistances in cardiogenic shock patients.

Eur Heart J Acute Cardiovasc Care 2020 Mar 20;9(2):102-107. Epub 2018 Aug 20.

Intensive Care Unit, Aix-Marseille University, France.

Objective: Impaired vascular tone plays an important role in cardiogenic shock. Doppler echocardiography provides a non-invasive estimation of systemic vascular resistance. The aim of the present study was to compare Doppler echocardiography with the transpulmonary thermodilution method for the assessment of systemic vascular resistance in patients with cardiogenic shock.

Methods: This prospective monocentric comparison study was conducted in a single cardiology intensive care unit (Hopital Nord, Marseille, France). We assessed the systemic vascular resistance index by both echocardiography and transpulmonary thermodilution in 28 patients admitted for cardiogenic shock, on admission and after the introduction of an inotrope or vasopressor treatment.

Results: A total of 35 paired echocardiographic and transpulmonary thermodilution estimations of the systemic vascular resistance index were compared. Echocardiography values ranged from 1309 to 3526 dynes.s.m/cm and transpulmonary thermodilution values ranged from 1320 to 3901 dynes.s.m/cm. A statistically significant correlation was found between echocardiography and transpulmonary thermodilution (=0.86, 95% confidence interval (CI) 0.74, 0.93; <0.0001). The intraclass correlation coefficient was 0.84 (95% CI 0.72, 0.92). The mean bias was -111.95 dynes.s.m/cm (95% CI -230.06, 6.16). Limits of agreement were -785.86, 561.96.

Conclusions: Doppler echocardiography constitutes an accurate non-invasive alternative to transpulmonary thermodilution to provide an estimation of systemic vascular resistance in patients with cardiogenic shock.
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http://dx.doi.org/10.1177/2048872618795514DOI Listing
March 2020

Adenosine Plasma Level and A2A Receptor Expression in Patients With Cardiogenic Shock.

Crit Care Med 2018 09;46(9):e874-e880

Department of Cardiology, Assistance Publique-Hôpitaux de Marseille, Hôpital Nord, Marseille, France.

Objectives: To investigate whether adenosine A2A receptors lead to vasodilation and positive inotropic function under stimulation and whether they play a role in the control of blood pressure in patients with cardiogenic shock.

Design: Prospective observational study.

Setting: Monocentric, Hopital Nord, Marseille, France.

Subjects: Patients with cardiogenic shock (n = 16), acute heart failure (n = 16), and acute myocardial infarction (n = 16).

Interventions: None.

Measurements And Main Results: Arterial adenosine plasma level and A2A receptor expression on peripheral blood mononuclear cells were evaluated by mass spectrometry and Western blot, respectively, at admission and after 24 hours. Hemodynamic parameters, including systemic vascular resistance, were also assessed. Mean adenosine plasma level at admission was significantly higher in patients with cardiogenic shock (2.74 ± 1.03 µM) versus acute heart failure (1.33 ± 0.27) or acute myocardial infarction (1.19 ± 0.27) (normal range, 0.4-0.8 µM) (p < 0.0001). No significant correlation was found between adenosine plasma level and systemic vascular resistance. Mean adenosine plasma level decreased significantly by 24 hours after admission in patients with cardiogenic shock (2.74 ± 1.03 to 1.53 ± 0.68; p < 0.001). Mean A2A receptor expression was significantly lower in patients with cardiogenic shock (1.18 ± 0.11) versus acute heart failure (1.18 ± 0.11 vs 1.39 ± 0.08) (p = 0.005).

Conclusions: We observed high adenosine plasma level and low A2A receptor expression at admission in patients with cardiogenic shock versus acute heart failure or acute myocardial infarction. This may contribute to the physiopathology of cardiogenic shock.
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http://dx.doi.org/10.1097/CCM.0000000000003252DOI Listing
September 2018

Response by Thuny et al to Letter Regarding Article, "Clinical Features, Management, and Outcomes of Immune Checkpoint Inhibitor-Related Cardiotoxicity".

Circulation 2018 05;137(22):2423-2424

Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille, Mediterranean University Cardio-Oncology Center, Unit of Heart Failure and Valvular Heart Diseases, Department of Cardiology, Hôpital Nord, Marseille, France (F.T., M.E., J.C.).

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http://dx.doi.org/10.1161/CIRCULATIONAHA.118.033783DOI Listing
May 2018

Uric acid levels are associated with endothelial dysfunction and severity of coronary atherosclerosis during a first episode of acute coronary syndrome.

Purinergic Signal 2018 06 6;14(2):191-199. Epub 2018 Apr 6.

Department of Cardiology, Hopital Nord, Marseille, France.

The role of serum uric acid in coronary artery disease has been extensively investigated. It was suggested that serum uric acid level (SUA) is an independent predictor of endothelial dysfunction and related to coronary artery lesions. However, the relationship between SUA and severity of coronary atherosclerosis evaluated via endothelial dysfunction using peripheral arterial tone (PAT) and the reactive hyperhemia index (RHI) has not been investigated during a first episode of acute coronary syndrome (ACS). The aim of our study was to address this point. We prospectively enrolled 80 patients with a first episode of ACS in a single-center observational study. All patients underwent coronary angiography, evaluation of endothelial function via the RHI, and SUA measurement. The severity of the coronary artery lesion was assessed angiographically, and patients were classified in three groups based on the extent of disease and Gensini and SYNTAX scores. Endothelial function was considered abnormal if RHI < 1.67. We identified a linear correlation between SUA and RHI (R = 0.66 P < 0.001). In multivariable analyses, SUA remained associated with RHI, even after adjustment for traditional cardiovascular risk factors and renal function. SUA was associated with severity of coronary artery disease. SUA is associated with severity of coronary atherosclerosis in patients with asymptomatic hyperuricemia. This inexpensive, readily measured biological parameter may be useful to monitor ACS patients.
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http://dx.doi.org/10.1007/s11302-018-9604-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940631PMC
June 2018