Comparison of myocardial fibrosis quantification methods by cardiovascular magnetic resonance imaging for risk stratification of patients with suspected myocarditis

Abstract Background Although the presence of late gadolinium enhancement (LGE) using cardiovascular magnetic resonance imaging (CMR) is a significant discriminator of events in patients with suspected myocarditis, no data are available on the optimal LGE quantification method. Methods Six hundred seventy consecutive patients (48 ± 16 years, 59% male) with suspected myocarditis were enrolled between 2002 and 2015. We performed LGE quantitation using seven different signal intensity thresholding methods based either on 2, 3, 4, 5, 6, 7 standard deviations (SD) above remote myocardium or full width at half maximum (FWHM). In addition, a LGE visual presence score (LGE-VPS) (LGE present/absent in each segment) was assessed. For each of these methods, the strength of association of LGE results with major adverse cardiac events (MACE) was determined. Inter-and intra-rater variability using intraclass-correlation coefficient (ICC) was performed for all methods. Results Ninety-eight (15%) patients experienced a MACE at a medium follow-up of 4.7 years. LGE quantification by FWHM, 2- and 3-SD demonstrated univariable association with MACE (hazard ratio [HR] 1.05, 95% confidence interval [CI]:1.02–1.08, p = 0.001; HR 1.02, 95%CI:1.00–1.04; p = 0.001; HR 1.02, 95%CI: 1.00–1.05, p = 0.035, respectively), whereas 4-SD through 7-SD methods did not reach significant association. LGE-VPS also demonstrated association with MACE (HR 1.09, 95%CI: 1.04–1.15, p < 0.001). In the multivariable model, FWHM, 2-SD methods, and LGE-VPS each demonstrated significant association with MACE adjusted to age, sex, BMI and LVEF (adjusted HR of 1.04, 1.02, and 1.07; p = 0.009, p = 0.035; and p = 0.005, respectively). In these, FWHM and LGE-VPS had the highest degrees of inter and intra-rater reproducibility based on their high ICC values. Conclusions FWHM is the optimal semi-automated quantification method in risk-stratifying patients with suspected myocarditis, demonstrating the strongest association with MACE and the highest technical consistency. Visual LGE scoring is a reliable alternative method and is associated with a comparable association with MACE and reproducibility in these patients. Trial registration number NCT03470571 . Registered 13th March 2018. Retrospectively registered.https://deepblue.lib.umich.edu/bitstream/2027.42/148145/1/12968_2019_Article_520.pd

Quantitative analysis in cardiac magnetic resonance imaging and prognosis

L'IRM cardiaque est un examen non invasif qui permet aujourd’hui de proposer une analyse multiparamétrique alliant notamment fonction, caractérisation tissulaire, perfusion, et appréciation de la fibrose. Cependant afin d'uniformiser ces analyses il convient de favoriser une interprétation objective des images obtenues passant par une étape de quantification de l'information. Nous avons suivi une cohorte de 195 patients ayant présenté un premier infarctus du myocarde avec sus décalage du segment ST et ayant bénéficié d'une revascularisation coronaire en phase aigüe avec succès. Des IRM ont été réalisées au cours de leur hospitalisation puis à 3 mois. Ont été investigués de façon quantitative les volumes ventriculaires, le stress pariétal systolique, la taille d'infarctus, la taille d'obstruction microvasculaire et la taille de l'épanchement péricardique. Une cohorte de 42 patients présentant une cardiomyopathie hypertrophique a également été étudiée par ECG et IRM. Nous avons débuté par une validation clinique comparative des méthodes de quantification semi-automatique de la taille d'infarctus. L’obtention du seuil par la méthode FWHM permet de mesurer la taille d’infarctus initial la mieux corrélée aux volumes ventriculaires à 3 mois. Nous avons également confronté et souligné les relations entre l’ECG et le phénotype des cardiomyopathies hypertrophiques documenté par IRM cardiaque. Nous montrons qu’il n’existe pas de critère ECG corrélé à la présence de fibrose myocardique dans cette pathologie ; à l’inverse la présence d’une onde q semble en relation avec la géométrie cardiaque tel qu’un rapport de la paroi septale sur latérale élevé. Nous avons également montré que les composantes de la déformation myocardique étaient altérées selon le degré de fibrose myocardique dans le post-infarctus. Nous montrons une altération plus marquée en cas d’obstruction microvasculaire et un caractère prédictif du strain longitudinal global pour la taille d’infarctus à 3 mois. Nos analyses soulignent l'intérêt d'une approche multiparamétrique pour préciser les déterminants d'une part de l'insuffisance cardiaque, d'autre part de la constitution d'un épanchement péricardique post-infarctus. Alors que la taille d’infarctus initiale est le meilleur marqueur de risque de développer un épisode d’insuffisance cardiaque pendant l’hospitalisation, c’est le stress pariétal systolique qui est le mieux relié aux épisodes d’insuffisance cardiaque après la sortie. Enfin, un épanchement péricardique était retrouvé chez 58.5% des patients avec une moyenne de 31.6±24.0 ml. Les paramètres associés en analyse multivariée étaient la taille d’infarctus, la présence d’une obstruction microvasculaire et le stress pariétal systolique. L’ensemble de nos résultats montre l’intérêt d’une approche quantitative et multiparamétrique de l’IRM cardiaque. Ses potentielles applications sont nombreuses dans le domaine de la recherche aussi bien descriptive que prospective et randomisée.The various aspect of cardiac function may now be investigated non-invasively by cardiac imaging. Cardiac magnetic resonance (CMR) allows to study multiple parameters in one time, including function, perfusion, tissular characteristics and fibrosis. There is a need to propose adequate and objective criteria for CMR analysis, which may be warranted by a quantitative analysis. We prospectively followed 195 patients with a first ST elevation myocardial infarction and successful revascularisation. CMR were performed at baseline and 3 months. We analysed ventricular volumes, systolic wall stress, infarct size, microvascular obstruction, and pericardial effusion extent. A cohort of 42 patients with hypertrophic cardiomyopathy were also studied. We demonstrated the clinical interest for semi-automated analysis of late gadolinium enhancement imaging. The use of the FWHM algorithm appeared strongly related to left ventricular volumes at 3 months. Then we depicted the lack of relationships between electrocardiograms and fibrosis in patients with hypertrophic cardiomyopathy. The presence of q waves appeared to be related to cardiac phenotype, namely higher septal to posterior ratios. We showed the impairment of myocardial deformations in regard of myocardial fibrosis following a myocardial infarction. We found a much depressed deformation in case of microvascular obstruction and an interest for longitudinal global strain for the prediction of infarct size at 3 months. We also studied the determinants of post-infarction heart failure on one part, pericardial effusion on the other, by the use of a CMR multiparametric approach. Infarct size and systolic wall stress were the best markers of in-hospital and post-discharge heart failure, respectively. A pericardial effusion was found in 58.5% of the patients with a mean size of 31.6±24.0 ml. The determinants by multivariate analysis were infarct size, microvascular obstruction and systolic wall stress. Our results highlighted the interest for a quantitative and multiparametric approach of CMR. Further applications are expected in both descriptive and randomized studies

Left ventricular function in a large cohort of pseudoxanthoma elasticum patients.

Pseudoxanthoma elasticum (PXE) is a rare autosomal recessive disorder characterized by the mineralization and fragmentation of elastic fibers in the skin, retina, and vascular walls. While there is no doubt that peripheral arterial disease is associated with PXE, several other cardiac complications have been linked with PXE, mainly based on case reports. It remains unclear, whether cardiac systolic or diastolic function impairment is a common complication of PXE.This study conducted systematic assessment of left ventricular systolic and diastolic function via standard echocardiography and two-dimensional strain imaging, in a large cohort of asymptomatic PXE patients (n = 75) and matched healthy controls (n = 30).PXE and controls did not differ in terms of any of the diastolic parameters tested: E-wave (82 ± 17 cm/s vs. 82 ± 13 cm/s, p = 0.890), E deceleration time (191.7 ± 55.6 ms vs. 190.0 ± 35.9 ms, p = 0.879), and E/Em ratio (7.1 ± 2.3 vs. 7.0 ± 1.8, p = 0.829). In addition, no significant differences were observed between PXE and control in terms of left ventricular volumes and ejection fraction, as well as global, basal, mid, and apex longitudinal strains.These findings revealed that preclinical cardiac dysfunction is uncommon in a large population of asymptomatic PXE patients

Longitudinal strain is a marker of microvascular obstruction and infarct size in patients with acute ST-segment elevation myocardial infarction.

OBJECTIVES: We assessed the value of speckle tracking imaging performed early after a first ST-segment elevation myocardial infarction (STEMI) in order to predict infarct size and functional recovery at 3-month follow-up. METHODS: 44 patients with STEMI who underwent revascularization within 12 h of symptom onset were prospectively enrolled. Echocardiography was performed 3.9 ± 1.2 days after myocardial reperfusion, assessing circumferential (CGS), radial (RGS), and longitudinal global (GLS) strains. Late gadolinium-enhanced cardiac magnetic imaging (CMR), for assessing cardiac function, infarct size, and microvascular obstruction (MVO), was conducted 5.6 ± 2.5 days and 99.4 ± 4.6 days after myocardial reperfusion. RESULTS: GLS was evaluable in 97% of the patients, while CGS and RGS could be assessed in 85%. Infarct size significantly correlated with GLS (R = 0.601, p<0.001), RGS (R = -0.405, p = 0.010), CGS (R = 0.526, p = 0.001), ejection fraction (R = -0.699, p<0.001), wall motion score index (WMSI) (R = 0.539, p = 0.001), and left atrial volume (R = 0.510, p<0.001). Baseline ejection fraction and GLS were independent predictors of 3-month infarct size. MVO mass significantly correlated with GLS (R = 0.376, p = 0.010), WMSI (R = 0.387, p = 0.011), and ejection fraction (R = -0.389, p = 0.011). In multivariate analysis, GLS was the only independent predictor of MVO mass (p = 0.015). Longitudinal strain >-6.0% within the infarcted area exhibited 96% specificity and 61% sensitivity for predicting the persistence of akinesia (≥ 3 segments) at 3-month follow-up. CONCLUSIONS: Speckle-tracking strain imaging performed early after a STEMI is easy-to-use as a marker for persistent akinetic territories at 3 months. In addition, GLS correlated significantly with MVO and final infarct size, both parameters being relevant post-MI prognostic factors, usually obtained via CMR

Myocarditis in Athletes Is a Challenge: Diagnosis, Risk Stratification, and Uncertainties

International audiencePresentation of myocarditis in athletes is heterogeneous and establishing the diagnosis is challenging with no current uniform clinical gold standard. The combined information from symptoms, electrocardiography, laboratory testing, echocardiography, cardiac magnetic resonance imaging, and in certain cases endomyocardial biopsy helps to establish the diagnosis. Most patients with myocarditis recover spontaneously; however, athletes may be at higher risk of adverse cardiac events. Based on scarce evidence and mainly autopsy studies and expert’s opinions, current recommendations generally advise abstinence from competitive sports ranging from a minimum of 3 to 6 months. However, the dilemma poses that (un)necessary prolonged disqualification of athletes to avoid adverse cardiac events can cause considerable disruption to training schedules and tournament preparation and lead to a decline in performance and ability to compete. Therefore, better risk stratification tools are imperatively needed. Using latest available data, this review contrasts existing recommendations and presents a new proposed diagnostic flowchart putting a greater focus on the use of cardiac magnetic resonance imaging in athletes with suspected myocarditis. This may enable cardiac caregivers to counsel athletes with suspected myocarditis more systematically and furthermore allow for pooling of more unified data. To modify recommendations regarding sports behavior in athletes with myocarditis, evidence, based on large multicenter registries including cardiac magnetic resonance imaging and endomyocardial biopsy, is needed. In the future, physicians might rely on combined novel risk stratification methods, by implementing both noninvasive and invasive tissue characterization methods

Left Atrial Remodeling Following ST‐Segment–Elevation Myocardial Infarction Correlates With Infarct Size and Age Older Than 70 Years

Background Following myocardial infarction, left ventricular remodeling (LVR) is associated with heart failure and cardiac death. At the same time, left atrial (LA) remodeling (LAR) is an essential part of the outcome of a wide spectrum of cardiac conditions. The authors sought to evaluate the correlates of LAR and its relationships with LVR after myocardial infarction. Methods and Results This is a retrospective analysis of 320 of 443 patients enrolled for study of LVR after ST‐elevation myocardial infarction. Left ventricular (LV) volumes, infarct size and LA volume index were assessed by cardiac magnetic resonance imaging during index hospitalization (day 6 [interquartile range, 4–8]) and after a 3‐month follow‐up. LAR was studied using a linear mixed model for repeated measurements. Overall, there was a decrease in LA volume index between 6 days and 3 months (43.9±10.4 mL versus 42.8±11.1 mL, P=0.003). Patients with changes in LA volume index >8% over time were older, with greater body mass index, lower LV ejection fraction, and larger infarct size. Unadjusted predictors of LAR were age older than 70 years, infarct size, anterior infarction, time to reperfusion, history of hypertension, LV end‐diastolic volume, and heart failure at day 6. Independent correlates were age older than 70 years (3.24±1.33, P=0.015) and infarct size (2.16±0.72 per 10% LV, P<0.001). LA remodeling was correlated with LV remodeling (r=0.372, P<0.001), but neither LA nor LV volumes at day 6 were related to LVR or LAR, respectively. Conclusions The authors found LA changes to occur in the months after myocardial infarction, with an overall decrease in LA volumes. While LAR coincided with LVR, the correlates for LAR were age older than 70 years and larger infarct size

Remote Ischemic Conditioning in a Model of Severe Renal Ischemia-Reperfusion Injury

International audienceIschemia-reperfusion (I/R) injury is a leading cause of acute renal dysfunction. Remote ischemic conditioning (rIC) is known to protect organs exposed to I/R. We sought to investigate whether rIC would influence renal function recovery in a severe renal I/R injury rat model. Rats were randomly assigned to four experimental groups following median laparotomy and right nephrectomy: Sham (n = 6); 30-min left renal ischemia (RI) only (n = 20); RI+rIC (n = 20) (four 5-min cycles of limb ischemia interspersed with 5-min limb reperfusion during RI); RI+erythropoietin pre-treatment (EPO) (n = 20). Renal function was evaluated by assessing blood urea nitrogen (BUN) and serum creatinine (Cr) levels before surgery and after 1 day of reperfusion. All animals were monitored for 7 days for survival analysis. BUN and Cr baseline levels did not significantly differ between groups. At Day 1, BUN and Cr were significantly higher than baseline values in all groups. BUN and Cr levels did not significantly differ at Day 1 between RI and RI+rIC (p = 0.68). Conversely, EPO pre-treatment injected 60 minutes before RI was associated with lower BUN and Cr levels compared to RI (p &lt; 0.001 and p = 0.003, respectively) and RI+rIC (p &lt; 0.001 and p = 0.001, respectively). In addition, 7-day survival rates were significantly higher in the Sham group (100%) compared to RI (50%; p = 0.039 vs Sham) and RI+rIC (45%; p = 0.026 vs Sham). Conversely, survival rate did not significantly differ between the Sham and RI+EPO groups (70%, p = 0.15). In conclusion, rIC affected neither acute renal dysfunction nor early mortality in a severe I/R renal injury rat model, contrary to EPO pre-treatment.</p

Echocardiographic data.

<p>LVEDV, Left ventricular end diastolic volume; LVESV, Left ventricular end systolic volume; LVEF, Left ventricular ejection fraction; LS, Longitudinal strain; E, early transmitral flow velocities; A, late transmitral flow velocities; Em, septal early diastolic velocities of the mitral annulus.</p><p>Data are presented as n (%), mean ± standard deviation.</p

Metabolomic Approach in STEMI-Patients Undergoing Left Ventricular Remodeling

Left ventricular remodeling (LVR) occurring after ST-segment elevation myocardial infarction (STEMI) is frequent and severe. We present a metabolomic approach as an attempt to reveal unknown biomarkers associated with post-STEMI LVR. Out of 192 consecutive patients with successfully revascularized STEMI, 32 presented LVR and were clinically matched with 32 no-LVR patients. They underwent cardiac magnetic resonance at baseline, three months and 12 months. Blood samples were collected during index hospitalization. Creatine kinase (CK) peak and inflammatory markers were higher for LVR patients compared to no-LVR patients (mean 3466 &plusmn; 2211 and 2394 &plusmn; 1615 UI/L respectively, p = 0.005 for CK peak; mean 35.9 &plusmn; 44.3 vs. 21.7 &plusmn; 30.4 mg/L respectively, p = 0.020 for C-reactive protein). Leukocyte and neutrophil counts were also higher for LVR patients (mean 12028 &plusmn; 2593/mL vs. 10346 &plusmn; 3626/mL respectively, p = 0.028 and mean 9035 &plusmn; 3036/mL vs. 7596 &plusmn; 3822/mL respectively, p &lt; 0.001). For metabolomic analysis, sphingomyelin C20:2 and symmetrical dimethylarginine were higher for LVR patients, but did not reach significance after the correction for the alpha risk. The metabolomic approach did not discriminate patients with and without LVR. However, common parameters that focus on infarction severity, such as infarct size and inflammatory markers, differed between the groups