Myriam Amsallem

Right heart imaging in patients with heart failure: a tale of two ventricles

Purpose of review The purpose is to describe the recent advances made in imaging of the right heart, including deformation imaging, tissue, and flow characterization by MRI, and molecular imaging. Recent findings Recent developments have been made in the field of deformation imaging of the right heart, which may improve risk stratification of patients with heart failure and pulmonary hypertension. In addition, more attention has been given to load adaptability metrics of the right heart; these simplified indices, however, still face challenges from a conceptual point of view. The emergence of novel MRI sequences, such as native T1 mapping, allows better detection and quantification of myocardial fibrosis and could allow better prediction of postsurgical recovery of the right heart. Other advances in MRI include four-dimensional flow imaging, which may be particularly useful in congenital heart disease or for the detection of early stages of pulmonary vascular disease. Summary The review will place the recent developments in right heart imaging in the context of clinical care and research.

Dual-Modality Activity-Based Probes as Molecular Imaging Agents for Vascular Inflammation

Macrophages are cellular mediators of vascular inflammation and are involved in the formation of atherosclerotic plaques. These immune cells secrete proteases such as matrix metalloproteinases and cathepsins that contribute to disease formation and progression. Here, we demonstrate that activity-based probes (ABPs) targeting cysteine cathepsins can be used in murine models of atherosclerosis to noninvasively image activated macrophage populations using both optical and PET/CT methods. The probes can also be used to topically label human carotid plaques demonstrating similar specific labeling of activated macrophage populations. Methods: Macrophage-rich carotid lesions were induced in FVB mice fed on a high-fat diet by streptozotocin injection followed by ligation of the left common carotid artery. Mice with carotid atherosclerotic plaques were injected with the optical or dual-modality probes BMV109 and BMV101, respectively, via the tail vein and noninvasively imaged by optical and small-animal PET/CT at different time points. After noninvasive imaging, the murine carotid arteries were imaged in situ and ex vivo, followed by immunofluorescence staining to confirm target labeling. Additionally, human carotid plaques were topically labeled with the probe and analyzed by both sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunofluorescence staining to confirm the primary targets of the probe. Results: Quantitative analysis of the signal intensity from both optical and PET/CT imaging showed significantly higher levels of accumulation of BMV109 and BMV101 (P < 0.005 and P < 0.05, respectively) in the ligated left carotid arteries than the right carotid or healthy arteries. Immunofluorescence staining for macrophages in cross-sectional slices of the murine artery demonstrated substantial infiltration of macrophages in the neointima and adventitia of the ligated left carotid arteries compared with the right. Analysis of the human plaque tissues by sodium dodecyl sulfate polyacrylamide gel electrophoresis confirmed that the primary targets of the probe were cathepsins X, B, S, and L. Immunofluorescence labeling of the human tissue with the probe demonstrated colocalization of the probe with CD68, elastin, and cathepsin S, similar to that observed in the experimental carotid inflammation murine model. Conclusion: We demonstrate that ABPs targeting the cysteine cathepsins can be used in murine models of atherosclerosis to noninvasively image activated macrophage populations using both optical and PET/CT methods. The probes could also be used to topically label human carotid plaques demonstrating similar specific labeling of activated macrophage populations. Therefore, ABPs targeting the cysteine cathepsins are potentially valuable new reagents for rapid and noninvasive imaging of atherosclerotic disease progression and plaque vulnerability.

Right Heart End-Systolic Remodeling Index Strongly Predicts Outcomes in Pulmonary Arterial Hypertension: Comparison With Validated Models.

Background— Right ventricular (RV) end-systolic dimensions provide information on both size and function. We investigated whether an internally scaled index of end-systolic dimension is incremental to well-validated prognostic scores in pulmonary arterial hypertension. Methods and Results— From 2005 to 2014, 228 patients with pulmonary arterial hypertension were prospectively enrolled. RV end-systolic remodeling index (RVESRI) was defined by lateral length divided by septal height. The incremental values of RV free wall longitudinal strain and RVESRI to risk scores were determined. Mean age was 49±14 years, 78% were female, 33% had connective tissue disease, 52% were in New York Heart Association class ≥III, and mean pulmonary vascular resistance was 11.2±6.4 WU. RVESRI and right atrial area were strongly connected to the other right heart metrics. Three zones of adaptation (adapted, maladapted, and severely maladapted) were identified based on the RVESRI to RV systolic pressure relationship. During a mean follow-up of 3.9±2.4 years, the primary end point of death, transplant, or admission for heart failure was reached in 88 patients. RVESRI was incremental to risk prediction scores in pulmonary arterial hypertension, including the Registry to Evaluate Early and Long-Term PAH Disease Management score, the Pulmonary Hypertension Connection equation, and the Mayo Clinic model. Using multivariable analysis, New York Heart Association class III/IV, RVESRI, and log NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) were retained (&khgr;2, 62.2; P<0.0001). Changes in RVESRI at 1 year (n=203) were predictive of outcome; patients initiated on prostanoid therapy showed the greatest improvement in RVESRI. Among right heart metrics, RVESRI demonstrated the best test–retest characteristics. Conclusions— RVESRI is a simple reproducible prognostic marker in patients with pulmonary arterial hypertension.

First Reported Human Case of Native Mitral Infective Endocarditis Caused by Streptococcus canis

A 65 year-old woman was admitted for acute heart failure and severe sepsis revealing definite mitral infective endocarditis with severe regurgitation, complicated by multiple embolisms. Three blood cultures yielded a group G Streptococcus canis strain. Urgent surgery was performed with bioprosthetic valve replacement. Polymerase chain reaction analysis of the valve found S canis DNA. Amoxicillin and gentamicin were given for 2 weeks followed by 4 weeks of amoxicillin alone. She reported contact with a dog without bite. S canis has been reported to cause zoonotic septicemia but to our knowledge, this is the first human case of native valve infective endocarditis.

Medically managed patients with non-ST-elevation acute myocardial infarction have heterogeneous outcomes, based on performance of angiography and extent of coronary artery disease.

Background: Medically managed individuals represent a high-risk group among patients with non–ST-elevation acute myocardial infarction (NSTE-AMI). We hypothesized that prognosis in this group is heterogeneous, depending on whether medical management was decided with or without coronary angiography (CAG). Methods: Using data from the French Registry of Acute ST-Elevation or Non–ST-Elevation Myocardial Infarction (FAST-MI), we analysed data from 798 patients with NSTE-AMI who were medically managed (i.e. without revascularization during the index hospitalization). Patients were categorized according to the performance of CAG and, if performed, to the extent of coronary artery disease (CAD). Results: There were marked differences in baseline demographics, according to whether CAG was performed and to the extent of CAD. While the overall mortality rate at five years was high (56.2%), it differed greatly between groups, with patients who did not undergo CAG having a higher mortality rate (77.4%) than patients who underwent CAG (36.7%, p<0.001), and a higher mortality rate even than patients with multivessel CAD (54.2%, p<0.001). By multivariable analysis, non-performance of CAG was an independent predictor of all-cause mortality among medically managed NSTE-AMI patients (adjusted hazard ratios (95% confidence intervals) 3.19 (1.79–5.67) at 30 days, 2.28 (1.60–3.26) at one year, and 1.63 (1.28–2.07) at five years; all p<0.001). Conclusion: Medically managed patients with NSTE-AMI are a heterogeneous group in terms of baseline characteristics and outcomes. The highest risk patients are those who do not undergo CAG. Non-performance of CAG is a strong predictor of death. (FAST-MI, NCT00673036).

Magnetic Resonance Imaging and Positron Emission Tomography Approaches to Imaging Vascular and Cardiac Inflammation

Inflammation plays a significant role in a wide range of cardiovascular diseases (CVDs). The numerous implications of inflammation in all steps of CVDs, including initiation, progression and complications, have prompted the emergence of noninvasive imaging modalities as diagnostic, prognostic and monitoring tools. In this review, we first synthesize the existing evidence on the role of inflammation in vascular and cardiac diseases, in order to identify the main targets used in noninvasive imaging. We chose to focus on positron emission tomographic (PET) and magnetic resonance imaging (MRI) studies, which offer the greatest potential of translation and clinical application. We detail the main preclinical and clinical studies in the following CVDs: coronary and vascular atherosclerosis, abdominal aortic aneurysms, myocardial infarction, myocarditis, and acute heart transplant rejection. We highlight the potential complementary roles of these imaging modalities, which are currently being studied in the emerging technology of PET/MRI. Finally, we provide a perspective on innovations and future applications of noninvasive imaging of cardiovascular inflammation. (Circ J 2016; 80: 1269-1277).

Exercise Strain Echocardiography in Patients With a Hemodynamically Significant Myocardial Bridge Assessed by Physiological Study

Background Although a myocardial bridge (MB) is often regarded as a benign coronary variant, recent studies have associated MB with focal myocardial ischemia. The physiological consequences of MB on ventricular function during stress have not been well established. Methods and Results We enrolled 58 patients with MB of the left anterior descending artery, diagnosed by intravascular ultrasound. Patients underwent invasive physiological evaluation of the MB by diastolic fractional flow reserve during dobutamine challenge and exercise echocardiography. Septal and lateral longitudinal strain (LS) were assessed at rest and immediately after exercise and compared with strain of matched controls. Absolute and relative changes in strain were also calculated. The mean age was 42.5±16.0 years. Fifty‐five patients had a diastolic fractional flow reserve ≤0.76. At rest, there was no significant difference between the 2 groups in septal LS (19.0±1.8% for patients with MB versus 19.2±1.5% for control, P=0.53) and lateral LS (20.1±2.0% versus 20.0±1.6%, P=0.83). With stress, compared with controls, patients with MB had a lower peak septal LS (18.9±2.6% versus 21.7±1.6%, P<0.001) and lower absolute (−0.1±2.1% versus 2.5±1.3%, P<0.001) and relative change (−0.6±11.2% versus 13.1±7.8%, P<0.001) in septal LS, whereas there was no significant difference in lateral LS. In multivariate analysis, diastolic fractional flow reserve and length were independent determinants of lower changes in septal LS. Conclusions Patients with a hemodynamically significant MB, determined by invasive diastolic fractional flow reserve, have significantly lower change in septal LS on exercise echocardiography, suggesting that septal LS may be useful for noninvasively assessing the hemodynamic significance of an MB.

Load Adaptability in Patients With Pulmonary Arterial Hypertension

Right ventricular (RV) adaptation to pressure overload is a major prognostic factor in patients with pulmonary arterial hypertension (PAH). The objectives were first to define the relation between RV adaptation and load using allometric modeling, then to compare the prognostic value of different indices of load adaptability in PAH. Both a derivation (n = 85) and a validation cohort (n = 200) were included. Load adaptability was assessed using 3 approaches: (1) surrogates of ventriculo-arterial coupling (e.g., RV area change/end-systolic area), (2) simple ratio of function and load (e.g., tricuspid annular plane systolic excursion/right ventricular systolic pressure), and (3) indices assessing the proportionality of adaptation using allometric pressure-function or size modeling. Proportional hazard modeling was used to compare the hazard ratio for the outcome of death or lung transplantation. The mean age of the derivation cohort was 44 ± 11 years, with 80% female and 74% in New York Heart Association class III or IV. Mean pulmonary vascular resistance index (PVRI) was 24 ± 11 with a wide distribution (1.6 to 57.5 WU/m2). Allometric relations were observed between PVRI and RV fractional area change (R2 = 0.53, p < 0.001) and RV end-systolic area indexed to body surface area right ventricular end-systolic area index (RVESAI) (R2 = 0.29, p < 0.001), allowing the derivation of simple ratiometric load-specific indices of RV adaptation. In right heart parameters, RVESAI was the strongest predictor of outcomes (hazard ratio per SD = 1.93, 95% confidence interval 1.37 to 2.75, p < 0.001). Although RVESAI/PVRI0.35 provided small incremental discrimination on multivariate modeling, none of the load-adaptability indices provided stronger discrimination of outcome than simple RV adaptation metrics in either the derivation or the validation cohort. In conclusion, allometric modeling enables quantification of the proportionality of RV load adaptation but offers small incremental prognostic value to RV end-systolic dimension in PAH.

Early Development of Right Ventricular Ischemic Lesions in a Novel Large Animal Model of Acute Right Heart Failure in Chronic Thromboembolic Pulmonary Hypertension

BACKGROUND Our aim was to develop a model of acute right heart failure (ARHF) in the setting of pulmonary hypertension and to characterize acute right ventricular lesions that develop early after hemodynamic restoration. METHODS AND RESULTS We used a described piglet model of chronic pulmonary hypertension (cPH) induced by pulmonary artery occlusions. We induced ARHF in animals with cPH (ARHF-cPH group, n = 9) by volume loading and iterative acute pulmonary embolism until hemodynamic compromise followed by dobutamine infusion for hemodynamic restoration before sacrifice for right ventricular tissue evaluation. The median duration of ARHF before sacrifice was 162 (135-189) minutes. Although ventriculoarterial coupling (measured with multibeat pressure-volume loops) and stroke volume decreased after iterative pulmonary embolism and improved with dobutamine, relative pulmonary to systemic pressure increased by 2-fold and remained similarly increased with dobutamine. Circulating high-sensitivity troponin I increased after hemodynamic restoration. We found an increase in right ventricular subendocardial and subepicardial focal ischemic lesions and in expression of autophagy-related protein LC3-II (Western blot) in the ARHF-cPH group compared with the cPH (n = 5) and control (n = 5) groups. CONCLUSIONS We developed and phenotyped a novel large animal model of ARHF on cPH in which right ventricular ischemic lesions were observed early after hemodynamic restoration.

Ticagrelor effectiveness overestimated by VASP index: Platelet inhibition by ticagrelor versus prasugrel in acute coronary syndrome patients according to platelet function tests

Platelet inhibition by ticagrelor versus prasugrel in acute coronary syndrome patients according to platelet function tests Jean-Guillaume Dillinger ⁎, Stephane Manzo Silberman , Claire Bal dit Sollier , Myriam Amsallem , Georgios Sideris , Sebastian Voicu , Patrick Henry , Ludovic Drouet b a Department of Cardiology, Inserm U942, Lariboisiere Hospital, AP-HP, Paris Diderot University, Paris, France b Angio-hematology and IVS, Lariboisiere Hospital, AP-HP, Paris Diderot University, Paris, France