Effets du sacubitril/valsartan sur la néprilysine et le métabolisme des peptides natriurétiques dans l'insuffisance cardiaque chronique : étude clinique mécanistique

Aim: this study aimed at evaluating the effects of sacubitril/valsartan on neprilysin (NEP), and the metabolism of natriuretic peptides in heart failure (HF) and providing additional mechanistic information on the mode of action of the drug. Methods and results: we enrolled 73 chronic HF patients who were switched from angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to sacubitril/valsartan. In addition to clinical and echocardiographic assessment, plasma biomarkers were measured at baseline, day 30 and day 90 after initiation of treatment. Sacubitril/valsartan led to decrease in New York Heart Association class and improvement of echocardiographic parameters, as well as a dose-dependent decrease in soluble NEP (sNEP) activity, while sNEP concentration remained unchanged. Neprilysin inhibition translated into an increase in its substrates such as atrial natriuretic peptide (ANP), substance P, and glucagon-like peptide 1, the latter translating into a decrease in fructosamine. Cardiac troponin and soluble ST2 levels, biomarkers of HF severity unrelated to NEP metabolism also decreased. While there was a ~4-fold increase in ANP, we observed no change in plasma brain natriuretic peptide (BNP) and plasma BNP activity, and a mild decrease in N-terminal proBNP (NT-proBNP) concentrations. Finally, we found a progressive increase in the relationship between BNP and NT-proBNP, which strongly correlated with an increase in T71 proBNP glycosylation (R2 = 0.94). Conclusion: sacubitril/valsartan rapidly and strongly reduced sNEP activity, leading to an increase in levels of NEP substrates.These data suggest a pleiotropic favourable impact of sacubitril/valsartan on the metabolism of HF patients with ANP rather than BNP as major effectors amongst natriuretic peptides.Objectif : cette étude visait à évaluer les effets du sacubitril/valsartan (LCZ696) sur l'activité de la néprilysine (NEP), le métabolisme des peptides natriurétiques dans l'insuffisance cardiaque chronique (ICC) et à fournir des informations supplémentaires sur le mode d'action du médicament. Méthodes et résultats : nous avons recruté 73 patients souffrant d'ICC chez qui nous avons introduits le LCZ696 en remplacement de l’IEC ou ARA2 préalable. En plus de l'évaluation clinique et échocardiographique, les biomarqueurs plasmatiques ont été mesurés avant introduction du LCZ696 puis à J3 à et J90 après le début du traitement. L’introduction de LCZ696 a été associée à une diminution, liée à la dose, de l’activité de la néprilysine soluble (sNEP), tandis que la concentration en sNEP n’était pas modifiée. L’inhibition de la NEP se traduit par une augmentation de ses substrats tels que le peptide natriurétique auriculaire (ANP), la substance P et le peptide 1 semblable au glucagon, ce dernier se traduisant par une diminution de la fructosamine. Les taux de Troponine cardiaque et de ST2 soluble, ainsi que les biomarqueurs de la sévérité de l'ICC non liés au métabolisme de la NEP ont également diminué. Malgré une augmentation d'environ 4 fois de l'ANP, nous n'avons observé aucune modification du peptide natriurétique cérébral (BNP) et de l'activité du BNP plasmatique, et une légère diminution de la concentration du proBNP N-terminal (NT-proBNP). Enfin, nous avons trouvé une augmentation progressive de la relation entre le BNP et le NT-proBNP, fortement corrélée à une augmentation de la glycosylation du proBNP (R2 = 0,94). Conclusion : le LCZ696 a rapidement et fortement réduit l'activité de la sNEP, amélioré le métabolisme du glucose en partie via l'augmentation du GLP-1 et modérément réduit le NT-proBNP tout en laissant le BNP plasmatique inchangé. Ces données remettent en cause l'explication mécanistique actuelle des effets bénéfiques du LCZ696 sur l'ICC

Cardiovascular Magnetic Resonance Imaging Pattern in Campylobacter jejuni-related Myocarditis

Background: Campylobacter jejuni (C. jejuni) is a common cause of mostly self-limiting enterocolitis. Although rare, myocarditis has been increasingly documented as a complication following campylobacteriosis. Such cases have occurred predominantly in younger males and involved a single causative species, namely C. jejuni. Case report: We report herein a case of myocarditis complicating gastroenteritis in a 23-year-old immunocompetent patient, caused by this bacterium with a favorable outcome. Cardiac magnetic resonance imagining was useful in establishing an early diagnosis. Conclusions: Myocarditis should be considered in younger patients presenting with chest pain and plasmatic troponin elevations. The occurrence of myocarditis complicating C. jejuni is reviewed

Characterization of non‐response to cardiac resynchronization therapy by post‐procedural computed tomography

International audienceIntroduction: Causes of non-response to cardiac resynchronization therapy (CRT) include mechanical dyssynchrony, myocardial scar, and suboptimal left ventricular (LV) lead location. We aimed to assess the utility of Late Iodine Enhancement Computed Tomography (LIE-CT) with image subtraction in characterizing CRT non-response. Methods: CRT response was defined as a decrease in LV end-systolic volume > 15% at 6 months. LIE-CT was performed after 6 months, and analyzed global and segmental dyssynchrony, myocardial scar, coronary venous anatomy, and position of LV lead relative to scar and segment of latest mechanical contraction. Results: We evaluated 29 patients (age 71 ± 12 years; 72% men) including 18 (62%) responders. All metrics evaluating residual dyssynchrony such as wall motion index and wall thickness index were worse in non-responders. There was no difference in presence and extent of scar between responders and non-responders. However, in non-responders, the LV lead was more often over an akinetic/dyskinetic area (72% vs. 22%, p = .007), a fibrotic area (64% vs. 8%, p = .0007), an area with myocardial thickness < 6 mm (82% vs. 22%, p = .002), and less often concordant with the region of maximal wall thickness (9% vs. 72%, p = .001). Among the 11 non-responders, eight had at least another coronary venous branch visualized by CT, including three (27%) coursing over a potentially interesting myocardial area (free of scar, with normal wall motion, and with a myocardial thickness ≥6 mm). Conclusion: LIE-CT with image subtraction allows a comprehensive characterization of patients after CRT and may provide clues for management of non-responders

Effects of sacubitril/valsartan on neprilysin targets and the metabolism of natriuretic peptides in chronic heart failure: a mechanistic clinical study

AIM This study aimed at evaluating the effects of sacubitril/valsartan on neprilysin (NEP), and the metabolism of natriuretic peptides in heart failure (HF) and providing additional mechanistic information on the mode of action of the drug. METHODS AND RESULTS We enrolled 73 chronic HF patients who were switched from angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to sacubitril/valsartan. In addition to clinical and echocardiographic assessment, plasma biomarkers were measured at baseline, day 30 and day 90 after initiation of treatment. Sacubitril/valsartan led to decrease in New York Heart Association class and improvement of echocardiographic parameters, as well as a dose-dependent decrease in soluble NEP (sNEP) activity, while sNEP concentration remained unchanged. Neprilysin inhibition translated into an increase in its substrates such as atrial natriuretic peptide (ANP), substance P, and glucagon-like peptide 1, the latter translating into a decrease in fructosamine. Cardiac troponin and soluble ST2 levels, biomarkers of HF severity unrelated to NEP metabolism also decreased. While there was a ∼4-fold increase in ANP, we observed no change in plasma brain natriuretic peptide (BNP) and plasma BNP activity, and a mild decrease in N-terminal proBNP (NT-proBNP) concentrations. Finally, we found a progressive increase in the relationship between BNP and NT-proBNP, which strongly correlated with an increase in T71 proBNP glycosylation (R = 0.94). CONCLUSION Sacubitril/valsartan rapidly and strongly reduced sNEP activity, leading to an increase in levels of NEP substrates. These data suggest a pleiotropic favourable impact of sacubitril/valsartan on the metabolism of HF patients with ANP rather than BNP as major effectors amongst natriuretic peptides

Coronary Computed Tomography Angiography Analysis of Calcium Content to Identify Non-culprit Vulnerable Plaques in Patients With Acute Coronary Syndrome

International audienceBackground: Aside from the culprit plaque, the presence of vulnerable plaques in patients with acute coronary syndrome (ACS) may be associated with future cardiac events. A link between calcification and plaque rupture has been previously described.Aim: To assess whether analysis of the calcium component of coronary plaques using CT angiography, coronary computed tomographic angiography (CCTA) can help to detect additional vulnerable plaques in patients with non-ST elevation myocardial infarction (NSTEMI).Materials and methods: Cross sectional study of consecutive patients referred for NSTEMI from 30 July to 30 August 2018 with CCTA performed before coronary angiography with systematic optical coherence tomography (OCT) analysis of all coronary arteries within 24 h of clinical onset of NSTEMI. Three types of plaques were defined: culprit plaques defined by angiography (vulnerable culprit plaques-VCP) - plaques with a fibrous cap thickness < 65 microns or thrombus in OCT (vulnerable non-culprit plaque-VNCP) - plaques with a fibrous cap thickness ≥ 65 microns in OCT (stable plaque-SP).Results: A total of 134 calcified plaques were identified in 29 patients (73% male, 59 ± 14 years) with 29(22%) VCP, 28(21%) VNCP and 77(57%) SP. Using CCTA analysis of the calcium component, factors associated with vulnerable plaques were longer calcification length, larger calcification volume, lower calcium mass, higher Agatston score plaque-specific (ASp), presence of spotty calcifications and an intimal position in the wall. In multivariate analysis, ASp, calcification length and spotty calcifications were independently associated to vulnerable plaques. There was no difference between VCP and VNCP.Conclusions: CCTA analysis of calcium component of the plaque could help to identify additional vulnerable plaques in NSTEMI patients

European Association of Cardiovascular Imaging survey on cardiovascular multimodality imaging in acute myocarditis

International audienceAims To assess the current role of cardiac imaging in the diagnosis, management, and follow-up of patients with acute myocarditis (AM) through a European Association of Cardiovascular Imaging survey. Methods and results A total of 412 volunteers from 74 countries responded to the survey. Most participants worked in tertiary centres (56%). All participants had access to echocardiography, while 79 and 75% had access to cardiac computed tomography angiography (CCTA) and cardiac magnetic resonance (CMR), respectively. Less than half (47%) had access to myocardial biopsy, and only 5% used this test routinely. CMR was performed within 7 days of presentation in 73% of cases. Non-ischaemic late gadolinium enhancement (LGE, 88%) and high-signal intensity in T2-weighted images (74%) were the most used diagnostic criteria for AM. CCTA was preferred to coronary angiography by 47% of participants to exclude coronary artery disease. Systematic prescription of beta-blockers and angiotensin-converting enzyme inhibitors was reported by 38 and 32% of participants. Around a quarter of participants declared considering LGE burden as a reason to treat. Most participants (90%) reported performing a follow-up echocardiogram, while 63% scheduled a follow-up CMR. The main reason for treatment discontinuation was improvement of left ventricular ejection fraction (89%), followed by LGE regression (60%). In two-thirds of participants, the decision to resume high-intensity sport was influenced by residual LGE. Conclusion This survey confirms the high utilization of cardiac imaging in AM but reveals major differences in how cardiac imaging is used and how the condition is managed between centres, underlining the need for recommendation statements in this topic

EACVI communication paper: first international young dedicated multimodal cardiovascular imaging simulation education event organized by the ESC.

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