Silent myocardial infarction fatty scars detected by coronary calcium score CT scan in diabetic patients without history of coronary heart disease.

OBJECTIVES: To evaluate the prevalence of intra-myocardial fatty scars (IMFS) most likely indicating previous silent myocardial infarction (SMI), as detected on coronary artery calcium (CAC) computed tomography (CT) scans in diabetic patients without history of coronary heart disease (CHD). METHODS: Diabetic patients screened for silent coronary insufficiency in a tertiary-care, university hospital between Jan-2015 and Dec-2016 were categorized according to their CAC score in two groups comprising 242 patients with CACS = 0 and 145 patients with CACS ≥ 300. CAC-CT scans were retrospectively evaluated for subendorcardial and transmural IMFS of the left ventricle. Adipose remodeling, patients' characteristics, cardiovascular risk factors and metabolic profile were compared between groups. RESULTS: Eighty-three (21%) patients with IMFS were identified, 55 (37.9%) in the group CACS ≥ 300 and 28 (11.6%) in the CACS = 0 (OR = 4.67; 95% CI = 2.78-7.84; p < 0.001). Total and average surface of IMFS and their number per patient were similar in both groups (p = 0.55; p = 0.29; p = 0.61, respectively). In the group CACS ≥ 300, patients with IMFS were older (p = 0.03) and had longer-lasting diabetes (p = 0.04). Patients with IMFS were older and had longer history of diabetes, reduced glomerular filtration rate, more coronary calcifications (all p < 0.05), and higher prevalence of carotid plaques (OR = 3.03; 95% CI = 1.43-6.39, p = 0.004). After correction for other variables, only a CACS ≥ 300 (OR = 5.12; 95% CI = 2.66-9.85; p < 0.001) was associated with an increased risk of having IMFS. CONCLUSIONS: In diabetic patients without known CHD, IMFSs were found in patients without coronary calcifications, although not as frequently as in patients with heavily calcified coronary arteries. It remains to be established if this marker translates in an upwards cardiovascular risk restratification especially in diabetic patients with CACS = 0. CLINICAL RELEVANCE STATEMENT: In diabetic patients without history of coronary heart disease, intramyocardial fatty scars, presumably of post-infarction origin, can be detected on coronary artery calcium CT scans more frequently, but not exclusively, if the coronary arteries are heavily calcified as compared to those without calcifications. KEY POINTS: • Intramyocardial fatty scars (IMFS), presumably of post-infarction origin, can be detected on coronary artery calcium (CAC) CT scans more frequently, but not exclusively, in diabetic patients with CACS ≥ 300 as compared to patients CACS = 0. • Patients with IMFS were older and had longer history of diabetes, reduced glomerular filtration rate, and more coronary calcifications. • Carotid plaques and CACS ≥ 300 were associated with an increased risk of having IMFS, about three and five folds respectively.

Coronary CT Angiography with Photon-counting CT: First-In-Human Results.

Background Spatial resolution, soft-tissue contrast, and dose-efficient capabilities of photon-counting CT (PCCT) potentially allow a better quality and diagnostic confidence of coronary CT angiography (CCTA) in comparison to conventional CT. Purpose To compare the quality of CCTA scans obtained with a clinical prototype PCCT system and an energy-integrating detector (EID) dual-layer CT (DLCT) system. Materials and Methods In this prospective board-approved study with informed consent, participants with coronary artery disease underwent retrospective electrocardiographically gated CCTA with both systems after injection of 65-75 mL of 400 mg/mL iodinated contrast agent at 5 mL/sec. A prior phantom task-based quality assessment of the detectability index of coronary lesions was performed. Ultra-high-resolution parameters were used for PCCT (1024 matrix, 0.25-mm section thickness) and EID DLCT (512 matrix, 0.67-mm section thickness). Three cardiac radiologists independently performed a blinded analysis using a five-point quality score (1 = insufficient, 5 = excellent) for overall image quality, diagnostic confidence, and diagnostic quality of calcifications, stents, and noncalcified plaques. A logistic regression model, adjusted for radiologists, was used to evaluate the proportion of improvement in scores with the best method. Results Fourteen consecutive participants (12 men; mean age, 61 years ± 17) were enrolled. Scores of overall quality and diagnostic confidence were higher with PCCT images with a median of 5 (interquartile range [IQR], 2) and 5 (IQR, 1) versus 4 (IQR, 1) and 4 (IQR, 3) with EID DLCT images, using a mean tube current of 255 mAs ± 0 versus 349 mAs ± 111 for EID DLCT images (P < .01). Proportions of improvement with PCCT images for quality of calcification, stent, and noncalcified plaque were 100%, 92% (95% CI: 71, 98), and 45% (95% CI: 28, 63), respectively. In the phantom study, detectability indexes were 2.3-fold higher for lumen and 2.9-fold higher for noncalcified plaques with PCCT images. Conclusion Coronary CT angiography with a photon-counting CT system demonstrated in humans an improved image quality and diagnostic confidence compared with an energy-integrating dual-layer CT. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Sandfort and Bluemke in this issue.

Clinical characteristics and outcome of elderly patients admitted in emergency department with an oxygen mismatch and type 2 myocardial infarction or myocardial injury.

BACKGROUND: Aging is a risk factor for type 2 myocardial infarction or myocardial injury, but few data are available on the elderly. We aimed to determine the factors associated with these pathologies and mortality in the elderly population and its age classes. METHODS: A retrospective cohort of all patients with oxygen mismatch (anemia, hypoxia, tachycardia, hypo/hypertension) for whom a troponin drawn was performed at admission in 2 emergency departments. Medical records were reviewed and classified as having type 2 myocardial infarction, acute or chronic myocardial injury, or no myocardial injury. RESULTS: Of the 824 patients who presented with oxygen mismatch, 675 (81.9%) were older than 65 years. Age over 85 years was a risk factor for acute non-ischemic myocardial injury (odds ratio, 95% confidence interval 2.23, 1.34-3.73). Non-ischemic myocardial injury was associated with hypoxemia, tachycardia, and acute renal failure in those older than 85 years, but only with acute infection in the 75-84-year-old group. Type 2 myocardial infarction was associated only with acute renal failure in the oldest group and, in the 75-84-year-old group, with acute heart failure and shock. Patients older than 85 years with acute myocardial injury, with or without infarction, had a higher in-hospital mortality, but subsequently, mortality depends more on the comorbidities than on age. CONCLUSION: Factors associated with type 2 myocardial infarction and acute non-ischemic myocardial injury in elderly admitted with oxygen mismatch vary notably between age classes. They are associated with in-hospital mortality but not with subsequent mortality when other cormorbities are taken into account.

Importance of infarct size versus other variables for clinical outcomes after PPCI in STEMI patients.

Despite promising experimental studies and encouraging proof-of-concept clinical trials, interventions aimed at limiting infarct size have failed to improve clinical outcomes in patients with ST-elevation myocardial infarction (STEMI). Our objective was to examine whether variables (cardiovascular risk factors, comorbidities, post-procedural variables, cotreatments) might be associated with clinical outcomes in STEMI patients independently from infarct size reduction. The present study was based on a post hoc analysis of the CIRCUS trial database (Clinicaltrials.gov NCT01502774) that assessed the clinical benefit of a single intravenous bolus of cyclosporine in 969 patients with anterior STEMI. Since cyclosporine had no detectable effect on clinical outcomes as well as on any measured variable, we here considered the whole study population as one group. Multivariate analysis was performed to address the respective weight of infarct size and variables in clinical outcomes. Multivariate analysis revealed that several variables (including gender, hypertension, renal dysfunction, TIMI flow grade post-PCI < 3, and treatment administered after PCI with betablockers and angiotensin-converting enzyme inhibitors) had per se a significant influence on the occurrence of [death or hospitalization for heart failure] at 1 year. The relative weight of infarct size and variables on the composite endpoint of [death or hospitalization for heart failure] at 1 year was 18% and 82%, respectively. Several variables contribute strongly to the clinical outcomes of STEMI patients suggesting that cardioprotective strategy might not only focus on infarct size reduction.

Cyclosporine before PCI in Patients with Acute Myocardial Infarction.

BACKGROUND: Experimental and clinical evidence suggests that cyclosporine may attenuate reperfusion injury and reduce myocardial infarct size. We aimed to test whether cyclosporine would improve clinical outcomes and prevent adverse left ventricular remodeling. METHODS: In a multicenter, double-blind, randomized trial, we assigned 970 patients with an acute anterior ST-segment elevation myocardial infarction (STEMI) who were undergoing percutaneous coronary intervention (PCI) within 12 hours after symptom onset and who had complete occlusion of the culprit coronary artery to receive a bolus injection of cyclosporine (administered intravenously at a dose of 2.5 mg per kilogram of body weight) or matching placebo before coronary recanalization. The primary outcome was a composite of death from any cause, worsening of heart failure during the initial hospitalization, rehospitalization for heart failure, or adverse left ventricular remodeling at 1 year. Adverse left ventricular remodeling was defined as an increase of 15% or more in the left ventricular end-diastolic volume. RESULTS: A total of 395 patients in the cyclosporine group and 396 in the placebo group received the assigned study drug and had data that could be evaluated for the primary outcome at 1 year. The rate of the primary outcome was 59.0% in the cyclosporine group and 58.1% in the control group (odds ratio, 1.04; 95% confidence interval [CI], 0.78 to 1.39; P=0.77). Cyclosporine did not reduce the incidence of the separate clinical components of the primary outcome or other events, including recurrent infarction, unstable angina, and stroke. No significant difference in the safety profile was observed between the two treatment groups. CONCLUSIONS: In patients with anterior STEMI who had been referred for primary PCI, intravenous cyclosporine did not result in better clinical outcomes than those with placebo and did not prevent adverse left ventricular remodeling at 1 year. (Funded by the French Ministry of Health and NeuroVive Pharmaceutical; CIRCUS ClinicalTrials.gov number, NCT01502774; EudraCT number, 2009-013713-99.).

Quantification of myocardial extracellular volume fraction with cardiac MR imaging for early detection of left ventricle involvement in systemic sclerosis.

PURPOSE: To determine whether extracellular volume fraction (ECV) quantification at cardiac magnetic resonance (MR) imaging can demonstrate subclinical left ventricle (LV) abnormalities in a cohort of consecutive systemic sclerosis (SS) patients, and to investigate the relationship between ECV and diastolic and systolic LV function. MATERIALS AND METHODS: All subjects gave their written informed consent. The protocol was approved by the ethics committee. ECV quantification with cardiac MR imaging was prospectively performed in 33 consecutive SS patients with normal echocardiography results and no late gadolinium chelate enhancement at MR imaging. Left ventricular and atrial volumes and peak circumferential strain were measured at cardiac MR imaging. Diastolic function was assessed at echocardiography. The results were compared with those of 16 age-matched healthy control subjects by using Mann-Whitney and Kruskal-Wallis tests. RESULTS: SS patients had significantly higher global ECV (P < .001) and higher local ECV for all basal and midventricular LV segments. Global ECV significantly correlated with left atrial volume (P = .002) and with the grade of diastolic dysfunction (P = .016). The majority of SS patients (63%; 21 of 33 patients) had a high global ECV and a low global systolic circumferential strain. CONCLUSION: ECV quantification can identify LV abnormalities at an early stage in SS patients. These abnormalities may reflect increase in diffuse myocardial fibrosis and are associated with diastolic LV dysfunction.

Postconditioning attenuates no-reflow in STEMI patients.

After acute myocardial infarction, the presence of no-reflow (or microvascular obstruction: MVO) has been associated with adverse left ventricular (LV) remodeling and worse clinical outcome. This study examined the effects of mechanical ischemic postconditioning on early and late MVO size in acute ST-elevation myocardial infarction (STEMI) patients. Fifty patients undergoing primary coronary angioplasty for a first STEMI with TIMI grade flow 0-1 and no collaterals were randomized to ischemic postconditioning (PC) (n = 25) or control (n = 25) groups. Ischemic PC consisted in the application of four consecutive cycles of a 1-min balloon occlusion, each followed by a 1-min deflation at the onset of reperfusion. Early (3 min post-contrast) and late (10 min post-contrast) MVO size were assessed by contrast-enhanced cardiac-MRI within 96 h after reperfusion. PC was associated with smaller early and late MVO size (3.9 ± 4.8 in PC versus 7.8 ± 6.6% of LV in controls for early MVO, P = 0.02; and 1.8 ± 3.1 in PC versus 4.1 ± 3.9% of LV in controls for late MVO; P = 0.01). This significant reduction was persistent after adjustment for thrombus aspiration, which neither had any significant effect on infarct size, nor on early or late MVO (P = NS for all). Attenuation of MVO was associated to infarct size reduction. Mechanical postconditioning significantly reduces MVO in patients with acute STEMI treated with primary angioplasty.

Outcome of patients admitted with oxygen mismatch and myocardial injury or infarction in emergency departments.

AIMS: To describe the outcomes and associated factors in a population of patients admitted to emergency departments with at least one condition of oxygen supply/demand imbalance, regardless of the troponin result or restrictive criteria for type 2 myocardial infarction. METHODS: We constituted a retrospective cohort of 824 patients. Medical records of patients having undergone a troponin assay were reviewed for selection and classification, and data including in-hospital stay and readmissions were collected. The reported outcomes are in-hospital mortality, 3-year mortality, and major adverse cardiovascular events. RESULTS: Patients with myocardial infarction or injury, either chronic or acute, were older, with more history of hypertension and chronic heart or renal failure but not for other cardiovascular risk factors and medical history. Acute myocardial injury and type 2 myocardial infarction were significantly associated with in-hospital mortality [odds ratio (OR) 3.71 95% confidence interval (CI) 1.90-7.33 and OR 3.15 95% CI 1.59-6.28, respectively]. However, the long-term mortality does not differ in comparison with patients presenting chronic myocardial injury or nonelevated troponin, ranging from 26.9 to 34.3%. Patients with chronic myocardial injury and type 2 myocardial infarction had more long-term major cardiovascular events (39.3 and 38.8%), but only for acute heart failure, and none was associated with this outcome after adjustment. CONCLUSION: Among patients admitted to emergency departments with an oxygen supply/demand imbalance, acute myocardial injury and type 2 myocardial infarction are strongly associated with in-hospital mortality. However, they are not associated with higher long-term mortality or major cardiovascular events after discharge, which tend to occur in elderly people with comorbidities.

What underlies sex differences in heart failure onset within the first year after a first myocardial infarction?

Background: Women are more likely to develop heart failure (HF) after myocardial infarction. However, diagnosis and reperfusion are often delayed. Objectives: To compare the prevalence of HF after primary percutaneous coronary intervention (PPCI)-treated ST segment myocardial infarction (STEMI) between sexes and to study its associations with comorbidities, infarct size, and left ventricular (LV) systolic and diastolic dysfunctions (DD). Methods: The patients with PPCI-treated anterior STEMI, from the CIRCUS study cohort, were followed up for 1 year and HF events were recorded. Evaluation of ejection fraction (LVEF) and DD were performed at baseline and at 1 year. The elevated LV filling pressure (LVFP) included Grades 2 and 3 DD. Results: Of the 791 patients from the CIRCUS study, 135 were women. At 1 year, the proportion of patients who developed HF was 21% among men and 34% among women (p = 0.001). In the subset of 407 patients with available diastolic parameters, the rate of HF was also higher in women. HF during the initial hospitalization was comparable between the sexes. However, women had a higher incidence of rehospitalization for HF within the first year after STEMI (14.1% vs. 4.1%, p = 0.005). Women were older with a higher prevalence of hypertension. The infarct size and LVEF were similar between the sexes. Elevated LVFP was observed more frequently in women than in men during the initial hospitalization and at 1 year (26% vs. 12%, p = 0.04, and 22% vs. 12%, p = 0.006, respectively). Interestingly, only initial elevated LVFP (HR 5.9, 95% CI: 2.4-14.5, p < 0.001), age, and hypertension were independently associated with rehospitalization for HF. Conclusions: After PPCI-treated anterior STEMI, despite comparable infarct size and LVEF, women presented a higher proportion of rehospitalization for HF than men. That was likely due to a greater DD associated with older age and hypertension.

Systolic myocardial dysfunction in patients with type 2 diabetes mellitus: identification at MR imaging with cine displacement encoding with stimulated echoes.

PURPOSE: To determine if cine displacement encoding with stimulated echoes (DENSE) can help to identify and determine the patterns of subclinical myocardial systolic dysfunction in patients with type 2 diabetes mellitus (DM) when compared with cine DENSE in control patients. MATERIALS AND METHODS: After obtaining approval from the institutional ethics committee and written informed consent from the patients, 37 patients with type 2 DM without overt heart disease and 23 age-matched control patients were prospectively included in the study. The patients underwent standard cine magnetic resonance (MR) imaging with two-dimensional cine DENSE acquisitions. Circumferential (Ecc) and radial (Err) systolic strains were measured on short-axis views at basal, mid, and apical left ventricular levels. Longitudinal strain (Ell) was measured on four- and two-chamber views. Statistical testing included the intraclass correlation coefficient and multiple linear regression analysis. RESULTS: The intraobserver intraclass correlation coefficient values were 0.85, 0.95, and 0.90, and the interobserver intraclass correlation coefficient values were 0.79, 0.91 and 0.80 for Ecc, Err, and Ell, respectively. The left ventricular ejection fraction was in the reference range and similar between the groups, and the patients with DM showed a decrease in Ecc (-14.4%±1.6 vs -17.0%±1.6, P<.001), Err (36.2%±10.9 vs 44.4%±9.9, P=.006) and Ell (-12.9%±2.1 vs -15.5%±1.6, P<.001) compared with the control patients. Finally, DM was independently associated with Ecc (P<.001), Err (P=.05) and Ell (P=.01) after adjustment for age, sex, hypertension, body mass index, and left ventricular mass. CONCLUSION: Cine DENSE, a motion-encoding MR imaging technique for myocardial strain assessment with high spatial resolution, appears to be useful in the identification of subclinical myocardial dysfunction in patients with DM.

Myocardial microvascular disease and major adverse cardiovascular events in patients with end-stage renal disease: rationale and design of the MICROCARD study.

BACKGROUND: Myocardial ischaemia, a consequence of coronary artery disease, is a major cause of death in patients with end-stage renal disease (ESRD). The pathophysiology and clinical presentation of coronary artery disease in ESRD patients seem to differ from non-ESRD patients with higher implication of myocardial microvascular disease (MMD), higher mortality, fewer myocardial infarctions, less significant coronary stenosis and low efficacy of well-established drugs such as statin and angiotensin-converting enzyme inhibitors. No study has investigated the presence of MMD and its clinical impact in ESRD patients. METHODS: We designed an observational prospective cohort study to investigate the prevalence of MMD and its association with major adverse cardiovascular events (MACE) in ESRD patients with a positive non-invasive test for myocardial ischaemia. Patients eligible for inclusion are those>18 years old receiving dialysis and/or undergoing investigation for kidney transplantation, who are referred to our renal clinic and meet all the inclusion criteria but none of the exclusion criteria. Patients with a positive test for myocardial ischaemia will be enrolled in the 'invasive group'. They will be further examined to detect simultaneously epicardial coronary stenosis by coronary angiography and MMD using pressure wire measurement of fractional flow reserve and coronary flow reserve followed by calculation of the index of microcirculatory resistance. Patients with a negative test for myocardial ischaemia will be enrolled in a 'control group' designed to verify whether the invasive group is indeed at high risk for MACE. Both groups will be followed up for 2 years to compare the incidence of MACE. CONCLUSION: The MICROCARD study will phenotype MMD and will investigate its relation with the incidence of MACE in ESRD patients with myocardial ischaemia. Clinicaltrial.gov NCT01291771.

First In-Human Results of Computed Tomography Angiography for Coronary Stent Assessment With a Spectral Photon Counting Computed Tomography.

OBJECTIVES: The aim of this study is to compare the image quality of in vivo coronary stents between an energy integrating detectors dual-layer computed tomography (EID-DLCT) and a clinical prototype of spectral photon counting computed tomography (SPCCT). MATERIALS AND METHODS: In January to June 2021, consecutive patients with coronary stents were prospectively enrolled to undergo a coronary computed tomography (CT) with an EID-DLCT (IQon, Philips) and an SPCCT (Philips). The study was approved by the local ethical committee and patients signed an informed consent. A retrospectively electrocardiogram-gated acquisition was performed with optimized matching parameters on the 2 scanners (EID-DLCT: collimation, 64 × 0.625 mm; kVp, 120, automatic exposure control with target current at 255 mAs; rotation time, 0.27 seconds; SPCCT: collimation, 64 × 0.275 mm; kVp, 120; mAs, 255; rotation time, 0.33 seconds). The injection protocol was the same on both scanners: 65 to 75 mL of Iomeron (Bracco) at 5 mL/s. Images were reconstructed with slice thickness of 0.67 mm, 512 matrix, XCB (Xres cardiac standard) and XCD (Xres cardiac detailed) kernel, iDose 3 for EID-DLCT and 0.25-mm slice thickness, 1024 matrix, Detailed 2 and Sharp kernel, and iDose 6 for SPCCT. Two experienced observers measured the proximal and distal external and internal diameters of the stents to quantify blooming artifacts. Regions of interest were drawn in the lumen of the stent and of the upstream coronary artery. The difference (Δ S-C) between the respective attenuation values was calculated as a quantification of stent-induced artifacts on intrastent image quality. For subjective image quality, 3 experienced observers graded with a 4-point scale the image quality of different parameters: coronary wall before the stent, stent lumen, stent structure, calcifications surrounding the stent, and beam-hardening artifacts. RESULTS: Eight patients (age, 68 years [interquartile range, 8]; all men; body mass index, 26.2 kg/m2 [interquartile range, 4.2]) with 16 stents were scanned. Five stents were not evaluable owing to motion artifacts on the SPCCT. Of the remaining, all were drug eluting stents, of which 6 were platinum-chromium, 3 were cobalt-platinum-iridium, and 1 was stainless steel. For 1 stent, no information could be retrieved. Radiation dose was lower with the SPCCT (fixed CT dose index of 25.7 mGy for SPCCT vs median CT dose index of 35.7 [IQ = 13.6] mGy; P = 0.02). For 1 stent, the internal diameter was not assessable on EID-DLCT. External diameters were smaller and internal diameters were larger with SPCCT (all P < 0.05). Consequently, blooming artifacts were reduced on SPCCT (P < 0.05). Whereas Hounsfield unit values within the coronary arteries on the 2 scanners were similar, the Δ S-C was lower for SPCCT-Sharp as compared with EID-DLCT-XCD and SPCCT-Detailed 2 (P < 0.05). The SPCCT received higher subjective scores than EID-DLCT for stent lumen, stent structure, surrounding calcifications and beam-hardening for both Detailed 2 and Sharp (all P ≤ 0.05). The SPCCT-Sharp was judged better for stent structure and beam-hardening assessment as compared with SPCCT-Detailed 2. CONCLUSION: Spectral photon counting CT demonstrated improved objective and subjective image quality as compared with EID-DLCT for the evaluation of coronary stents even with a reduced radiation dose.

Atrial premature activity detected after an ischaemic stroke unveils atrial myopathy.

BACKGROUND: Recent publications suggest that left atrial (LA) myopathy is a potential source of thromboembolism, independent of atrial fibrillation. AIMS: We sought to investigate whether the presence of atrial premature activity after an ischaemic stroke is associated with LA remodelling and dysfunction, and might be a surrogate marker of LA myopathy. METHODS: After an ischaemic stroke or a transient ischaemic attack, patients without known atrial fibrillation or overt heart disease were included prospectively in the study. All patients had a standard workup, including ambulatory Holter electrocardiogram monitoring and transthoracic echocardiography. In some patients, transoesophageal echocardiography was also performed. Anatomical and functional LA remodelling were assessed using minimal and maximal volumes and LA emptying fraction in two-dimensional and three-dimensional echocardiography. Patients were separated into two groups according to the burden of atrial premature complexes (APCs), measured by Holter electrocardiography. RESULTS: Among 148 eligible patients recruited from October 2015 to May 2016, 93 were included in the group with non-frequent APCs (nf-APC:<100 APCs/24hours) and 43 in the group with frequent APCs (f-APC:>100 APCs/24hours). Twelve patients had paroxysmal atrial fibrillation, and were not included in the statistical analysis. Maximal and minimal indexed LA volumes were significantly higher in the f-APC group than in the nf-APC group (P<0.01). LA emptying fraction was worse in the f-APC group than in the nf-APC group. In addition, LA appendage emptying velocity was impaired in the f-APC group, and was correlated with LA remodelling variables, especially LA emptying fraction (r=0.621). CONCLUSIONS: After an ischaemic stroke or a transient ischaemic attack, excessive APCs are associated with LA remodelling. Thus, LA dilatation and dysfunction reflect early LA myopathy, which might itself be responsible for cardioembolic stroke.

Bis(monoacylglycero)phosphate, a new lipid signature of endosome-derived extracellular vesicles.

Bis(monoacylglycero)phosphate (BMP), also known as lysobisphosphatidic acid (LBPA), is a phospholipid specifically enriched in the late endosome-lysosome compartment playing a crucial role for the fate of endocytosed components. Due to its presence in extracellular fluids during diseases associated with endolysosomal dysfunction, it is considered as a possible biomarker of disorders such as genetic lysosomal storage diseases and cationic amphiphilic drug-induced phospholipidosis. However, there is no true validation of this biomarker in human studies, nor a clear identification of the carrier of this endolysosome-specific lipid in biofluids. The present study demonstrates that in absence of any sign of renal failure, BMP, especially all docosahexaenoyl containing species, are significantly increased in the urine of patients treated with the antiarrhythmic drug amiodarone. Such urinary BMP increase could reflect a generalized drug-induced perturbation of the endolysosome compartment as observed in vitro with amiodarone-treated human macrophages. Noteworthy, BMP was associated with extracellular vesicles (EVs) isolated from human urines and extracellular medium of human embryonic kidney HEK293 cells and co-localizing with classical EV protein markers CD63 and ALIX. In the context of drug-induced endolysosomal dysfunction, increased BMP-rich EV release could be useful to remove excess of undigested material. This first human pilot study not only reveals BMP as a urinary biomarker of amiodarone-induced endolysosomal dysfunction, but also highlights its utility to prove the endosomal origin of EVs, also named as exosomes. This peculiar lipid already known as a canonical late endosome-lysosome marker, may be thus considered as a new lipid marker of urinary exosomes.

Predictive value of early cardiac magnetic resonance imaging functional and geometric indexes for adverse left ventricular remodelling in patients with anterior ST-segment elevation myocardial infarction: A report from the CIRCUS study.

BACKGROUND: Postinfarction adverse left ventricular (LV) remodelling is strongly associated with heart failure events. Conicity index, sphericity index and LV global functional index (LVGFI) are new LV remodelling indexes assessed by cardiac magnetic resonance (CMR). AIM: To assess the predictive value of the new indexes for 1-year adverse LV remodelling in patients with anterior ST-segment elevated myocardial infarction (STEMI). METHODS: CMR studies were performed in 129 patients with anterior STEMI (58±12 years; 78% men) from the randomized CIRCUS trial (CMR substudy) treated with primary percutaneous coronary intervention and followed for the occurrence of major adverse cardiovascular events (MACE) (death or hospitalization for heart failure). Conicity index, sphericity index, LVGFI, infarct size and microvascular obstruction (MVO) were assessed by CMR performed 5±4 days after coronary reperfusion. Adverse LV remodelling was defined as an increase in LV end-diastolic volume of ≥15% by transthoracic echocardiography at 1 year. RESULTS: Adverse LV remodelling occurred in 27% of patients at 1 year. Infarct size and MVO were significantly predictive of adverse LV remodelling: odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01-1.05 (P<0.001) and OR 1.12, 95% CI 1.05-1.22 (P<0.001), respectively. Among the newly tested indexes, only LVGFI was significantly predictive of adverse LV remodelling (OR 1.10, 95% CI 1.03-1.16; P=0.001). In multivariable analysis, infarct size remained an independent predictor of adverse LV remodelling at 1 year (OR 1.05, 95% CI 1.02-1.08; P<0.001). LVGFI and infarct size were associated with occurrence of MACE: OR 1.21, 95% CI 1.08-1.37 (P<0.001) and OR 1.02, 95% CI 1.00-1.04 (P=0.018), respectively. Conicity and sphericity indexes were not associated with MACE. CONCLUSIONS: LVGFI was associated with adverse LV remodelling and MACE 1 year after anterior STEMI.

Influence of afterload on left ventricular radial and longitudinal systolic functions: a two-dimensional strain imaging study.

AIMS: This study aimed to assess the influence of afterload alteration on radial (R) and longitudinal (L) left ventricular (LV) systolic regional functions. METHODS AND RESULTS: We analysed systolic myocardial function by two-dimensional strain (2D-S) and sonomicrometry (SS) in an experimental pig model of aortic banding. Both radial and longitudinal functions were analysed in six open-chest pigs under various loading conditions: baseline and graded aortic banding (subsequent increase in LV pressure of 10, 20, and 40 mmHg). Both systolic 2D-S(long) and 2D-S(rad) were significantly correlated with SS(long) and SS(rad) (r = 0.63, P < 0.001 and r = 0.65, P < 0.01, respectively). At a low increase in LV afterload, 2D-S(rad) was still preserved whereas 2D-S(long) significantly decreased. When LV afterload was subsequently increased, both 2D-S(rad) and 2D-S(long) significantly decreased. Difference in dependence to wall stress might explain these different behaviours. CONCLUSION: 2D-S shows a different response in longitudinal and radial functions to increased afterload. Longitudinal function is early impaired, whereas radial function remains preserved. This finding justifies the combined assessment of both radial and longitudinal regional myocardial functions to characterize myocardial dysfunction and might help to better identify the transition to heart failure in pressure-overload cardiomyopathy.

Efficacy of TIMOLOL nasal spray as a treatment for epistaxis in hereditary hemorrhagic telangiectasia. A double-blind, randomized, placebo-controlled trial.

Hereditary hemorrhagic telangiectasia is a rare vascular genetic disease. Epistaxis is the most frequent and disabling manifestation, and timolol appears to be a new therapeutic option as non-selective beta-blockers have in vitro and in vivo anti-angiogenic properties. Our main objective was to evaluate the efficacy of TIMOLOL nasal spray as a treatment for epistaxis in hereditary hemorrhagic telangiectasia. This study is a single-center, randomized, phase 2, double-blind placebo-controlled study with an allocation ratio of 1:1. It was proposed to patients with hereditary hemorrhagic telangiectasia monitored at the French Reference Center, and we included patients aged over 18 years, diagnosed with hereditary hemorrhagic telangiectasia and epistaxis. The treatment was self-administered by the patient with a posology of one spray (50 µL) of timolol 0.5% or placebo in each nostril twice a day for 28 consecutive days. The primary efficacy endpoint was mean monthly epistaxis duration, assessed by monitoring epistaxis grids. A total of 58 patients were randomized and treated. The baseline characteristics were similar in the 2 groups. Mean monthly epistaxis duration measured at 3 months was not significantly different in the 26 patients receiving the drug in comparison with the placebo group (p = 0.54). Toxicity was low and no severe adverse events were reported. One limitation is that we included all HHT patients with nosebleeds and did not take into account history of nasal surgery or nasal crusts. Timolol, administered by nasal spray at a dose of 0.25 mg in each nostril twice a day for 28 consecutive days, did not improve epistaxis in patients with hereditary hemorrhagic telangiectasia at 4 months after the beginning of the treatment.