Retrospective Study of 573 Patients with Heart Failure Evaluated for Coronary Artery Disease at Toulouse University Center, France.

BACKGROUND Heart failure (HF) most commonly occurs due to ischemic heart disease from stenotic coronary artery disease (CAD). HF is classified into 3 groups based on the percentage of the ejection fraction (EF): reduced (HFrEF), mid-range (HFmrEF), and preserved (HFpEF). This retrospective study included 573 patients who presented with HF based on the evaluation of EF and were evaluated for CAD by coronary angiography before undergoing coronary angioplasty at a single center in Toulouse, France. MATERIAL AND METHODS This retrospective observational study included patients recently diagnosed with HF or acute decompensation of chronic HF and referred for coronary angiography at Toulouse University Hospital between January 2019 and May 2020. RESULTS Significant CAD was found in 55.8%, 55%, and 55% of the whole population, HFpEF, and HFrEF groups, respectively. Older age, male sex, and diabetes mellitus were the main risk factors for ischemic HF. Except for age and sex, patients with ischemic HFpEF were comparable to those with non-ischemic HFpEF, unlike the ischemic HFrEF group, which had more common cardiovascular risk factors than the non-ischemic HFrEF group. The ischemic HFpEF group had an older age and higher rate of dyslipidemia than the ischemic HFrEF group. CONCLUSIONS At our center, CAD was diagnosed in more than half of patients who presented with heart failure with preserved or reduced EF. Older age and male sex were the common risk factors in patients with HFpEF and HFrEF.

Quantitative assessment of tricuspid regurgitation using right and left ventricular stroke volumes obtained from tomographic equilibrium radionuclide ventriculography.

BACKGROUND: Quantitative assessment of valve regurgitation using volumetric method by comparing right and left ventricular stroke volumes is still under investigations. AIMS: To investigate the accuracy of tomographic equilibrium radionuclide ventriculography (t-ERV) for the quantification of tricuspid regurgitation (TR). METHODS AND RESULTS: Sixty-one patients (44 men; mean age 59 ± 12 years) who underwent both t-ERV and transthoracic echocardiography (TTE) studies within 2 weeks for right ventricular systolic function assessment were eligible for inclusion. A sub-group of 22 patients underwent both t-ERV and CMR. Patients with mitral/aortic regurgitation by TTE were excluded of the study. TR regurgitant volume (RVol) was calculated using the proximal isovelocity surface area (PISA) method from TTE and the volumetric method (right ventricular stroke volume minus left ventricular stroke volume) from t-ERV. There was a significant correlation between RVol as assess by ERV and by TTE (R = 0.95, P < 0.0001). Intraclass correlation coefficient between TTE and ERV for TR quantification was 0.95 (P < 0.0001). Among patients who underwent CMR, the correlation between RVol obtained by TTE and by t-ERV and CMR were R = 0.81 and R = 0.75, respectively (all P < 0.0001). CONCLUSION: TR assessment using the t-ERV correlates well with PISA from TTE in patients referred for right ventricular systolic function assessment.

Severe mitral regurgitation recurrence after successful percutaneous mitral edge-to-edge repair by Mitraclip in primary mitral regurgitation: Insights from a three-dimensional echocardiography study.

BACKGROUND: The sustainability of the results of Mitraclip procedures is a source of concern. AIMS: To investigate risk factors of severe mitral regurgitation (MR) recurrence after Mitraclip in primary MR. METHODS AND RESULTS: Eighty-three patients undergoing successful Mitraclip procedures were retrospectively included. Valve anatomy and Mitraclips placement were comprehensively analyzed by post-processing 3D echocardiographic acquisition. The primary composite endpoint was the recurrence of severe MR. The average age was 83±7 years-old, 37 (44%) were female. Median follow-up was 381 days (IQR 195-717) and 17 (20%) patients reached the primary endpoint. Main causes of recurrence of severe MR were relapse of a prolapse (64%) and single leaflet detachment (23%). Posterior coaptation line length (HR 1.06 95%CI 1.01-1.12 p = 0.02), poor imaging quality (HR 3.84, 95%CI 1.12-13.19; p = 0.03), and inter-clip distance (HR 1.60, 95%CI 1.27-2.02; p < 0.01) were associated with the occurrence of the primary endpoint. CONCLUSIONS: Recurrence of severe MR after a MitraClip procedure for primary MR results from a complex interplay between anatomical (tissue excess) and procedural criteria (quality of ultrasound guidance and MitraClips spacing).

Participating in Sports After Mitral Valve Repair for Primary Mitral Regurgitation: A Retrospective Cohort Study.

OBJECTIVE: Participating in either competitive or leisure sports is restrictive after surgical mitral valve repair (MVR). In this study, we examine the impact of sports on outcomes after MVR. DESIGN: Retrospective cohort study. SETTING: Patients aged 18 to 65 years who underwent a first-time MVR for primary mitral regurgitation (MR) in a tertiary care center. PATIENTS: One hundred twenty-one consecutive patients were included in the study. The exclusion criteria were as follows: other concomitant procedures, early perioperative death or repeat intervention, noncardiac death or endocarditis during follow-up, and general contraindications for normal physical activity. ASSESSMENT OF RISK FACTORS: Participation in sports was quantified by the number of hours per week during the past 6 months, classified according to the Mitchell classification and assessed with the International Physical Activity Questionnaire (IPAQ) short form. MAIN OUTCOME MEASURES: The primary composite endpoint was MVR failure defined as MR grade ≥2 or mean transmitral gradient ≥8 mm Hg, signs and symptoms of heart failure, or late-onset postoperative AF (>3 months). RESULTS: The mean age was 50 ± 11 years, and there were 85 (71%) men. The median follow-up was 34 months [interquartile range (IQR): 20-50]. Fifty-six (46%) patients participated in sports regularly (median of 3 h/wk; IQR: 2-5). Twenty (17%) patients reached the primary composite endpoint with no correlation with participation in sports (P = 0.537), IPAQ categories (P = 0.849), in any of the Mitchell classification subgroups and a high level of participation in sports ≥6 hours (P = 0.679). CONCLUSIONS: Sports seem to be unrelated to the worst outcome after MVR.

Pattern of myocardial 99mTc-HMDP uptake and impact on myocardial function in patients with transthyretin cardiac amyloidosis.

AIMS: The purpose of the study was to describe the pattern of 99mTc-labeled phosphate agents myocardial uptake by scintigraphy and explore its impact on left ventricular (LV) functions in transthyretin cardiac amyloidosis (TTR-CA). METHODS: Fifty patients with TTR-CA underwent 99mTc- hydroxymethylene-diphosphonate (99mTc-HMDP) scintigraphy and echocardiography with measure of LV thickness, longitudinal strain (LS), systolic and diastolic functions. Cardiac retention by scintigraphy was assessed by visual scoring and the heart/whole body (H/WB) ratio was calculated by dividing counts in the heart by counts in late whole-body images. RESULTS: The mean population age was 79 ± 10 years. Mean H/WB ratio was 12 ± 7. Myocardial 99mTc-HMDP uptake on segments 5, 6, 7, 8, 11, 12, 13, 14, 16, and 17 was correlated with H/WB ratio. Mean LVEF and global LS were 51 ± 10% and - 10 ± 3%, respectively. H/WB ratio was correlated with global LS (R = 0.408, P = .003), Ea (R = - 0.566, P < .001) and mean left ventricular wall thickness (R = 0.476, P < .001) but not with LVEF (R = - 0.109, P = .453). Segmental myocardial uptake was slightly correlated with segmental LS (R = 0.152, P < .001). H/WB ratio was not correlated with NT-proBNP levels (R = 0.219, P = .148) neither E/Ea ratio (R = 0.204, P = .184). CONCLUSION: These findings show the relationship between bone tracer myocardial uptake and LV functions in patients with TTR cardiac amyloidosis.

Cardiac impact of arteriovenous fistulas: what tools to assess?

The relationship between arteriovenous access flow (Qa) and cardiovascular changes is complex. Several studies have shown cardiac remodeling and symptoms of heart failure for high-flow arteriovenous fistulas (AVF). To evaluate the early cardiovascular impact of AVF. Forty-seven patients with an AVF, hospitalized for the evaluation of high-flow AVF or a pre-kidney transplant assessment were included. We collected clinical and biological data. We also collected data of the assessment by transthoracic echocardiography, functional evaluation by 6-min-walk test and peak oxygen consumption, and measurement of coronary flow reserve by dynamic myocardial perfusion imaging. The measurement of Qa was performed by color Doppler ultrasound and then indexed to the body surface area (Qai) and to the cardiac output (CO) (Qa/CO). Patients were poorly symptomatic (18 and 1 patients NYHA stage 2 and 3, respectively). There was no correlation between Qa, Qai, or Qa/CO and functional status, assessed by peak oxygen consumption (P = 0.891; P = 0.803; P = 0.939, respectively). Symptomatic patients did not have higher Qa, Qai or Qa/CO than asymptomatic (2260 vs 2197 mL/min, P = 0.402; 1257 vs 1256 mL/min/m2, P = 0.835; and 34% vs 37%, P = 0.701, respectively). There was no correlation between Qa, Qai or Qa/CO and left ventricular end-diastolic volume or left ventricular ejection fraction. There was no correlation between coronary flow reserve and these 3 parameters of vascular access flow. However, the global longitudinal strain (GLS) was correlated with Qa and Qa/CO (R = 0.331, P = 0.023 and R = 0.380, P = 0.008, respectively). Increase of Qa or Qa/CO was associated with an alteration of the GLS. A cut-off value of 2250 mL/min for Qa allowed 83% sensitivity and 63% specificity for detecting an alteration of the GLS > - 18%. A cut-off value of 33% for Qa/CO allowed 92% sensitivity and 65% specificity. Impact of AVF on cardiac parameters is weak. However, GLS is the first parameter to be impacted by the flow of the fistula. Systematic transthoracic echocardiography evaluation with measurement of GLS should be proposed for all patients with Qa > 2250 mL/min or Qa/CO > 33%, to detect those at higher risk of cardiac impact of the AVF.

What is the most useful imaging parameter to explore the prognostic value of the right ventricular function at the time of multimodality cardiovascular imaging?

BACKGROUND: Right ventricular (RV) function is a powerful independent predictor of adverse heart failure outcomes. The aim of this study was to compare the predictive value of main RV systolic imaging parameters for outcome. METHODS: Seventy-nine patients underwent comprehensive cardiovascular imaging modalities including transthoracic echocardiography, cardiac magnetic resonance (CMR) imaging, and tomographic equilibrium radionuclide ventriculography (ERV) for the assessment of RV function. The composite primary endpoint (CPE) was defined by the occurrence of death, heart transplantation, implantation of a left ventricular assist device, or new-onset acute heart failure. RESULTS: During a mean follow-up of 13 ± 9 months, 15 (19%) patients reached the CPE. The areas under the receiver operator characteristic curves for the prediction of the CPE were 0.922 (P < .001), 0.913 (P < .001), 0.906 (P < .001), 0.849 (P = .002), 0.837 (P = .003), 0.799 (P = .009), 0.792 (P = .011), 0.753 (P = .026), 0.720 (P = .053), and 0.608 (P = .346) for integral systolic S' wave tricuspid annular velocity, RV free wall longitudinal strain (RVFWLS), RV fractional area change, tricuspid annular plane systolic excursion, RV ejection fraction (RVEF) by CMR using the 4-chamber slices, peak systolic S' wave tricuspid annular velocity, RVEF by CMR using short-axis slices, RVEF by ERV, RV myocardial performance index, and RV myocardial acceleration during isovolumic contraction, respectively. CONCLUSION: Echocardiographic parameters, and particularly integral systolic S' wave tricuspid annular velocity and RVFWLS, have the best prognostic performance.

Impact of right ventricular systolic function after heart transplantation on exercise capacity.

BACKGROUND: Right ventricular (RV) systolic parameters are difficult to assess in heart transplant recipients (HTRs) compared to healthy people because of discordant data, and their impact on exercise capacity remains undefined. We sought to retrospectively assess the impact of RV systolic function on exercise capacity after heart transplantation. METHODS: We analyzed data from 61 HTRs who underwent transthoracic echocardiography (TTE), cardiac magnetic resonance imaging (CMR), and exercise capacity assessment by 6-minute walking test (6MWT) and cardiopulmonary exercise testing (CPET) at 1- and 2-year follow-ups. RESULTS: Transthoracic echocardiography RV longitudinal systolic function including tricuspid annular plan systolic excursion (TAPSE), peak systolic S' wave tricuspid annular velocity (PSVtdi) and RV free wall longitudinal strain was decreased at 1 year (respectively, 15 ± 3 mm, 10 ± 3 cm/s, and -19 ± 5%) and at 2 years (respectively, 15 ± 3 mm, 10 ± 2 cm/s, and -20 ± 5%) with no significant difference between both evaluations; meanwhile, RV ejection fraction (RVEF) measured by CMR was preserved. Mean percentage of predicted peak oxygen consumption was altered, but improved between the first and second year (55 ± 18 vs 60 ± 18%, P = .038). PSVtdi was weakly correlated with 6MWT distance (r = .426, P = .017) and RVEF with the predicted distance at 6MWT (r = .410, P = .027) at the 1-year follow-up. CONCLUSIONS: Despite decreasing values, RV longitudinal systolic function has a weak impact on exercise capacity of HTRs. PSVtdi and RVEF are the most pertinent parameters to assess the impact of RV systolic function on exercise capacity after heart transplantation. These results should lead to redefine normal RV systolic function thresholds for HTRs.

Prognostic impact of myocardial perfusion single photon emission computed tomography in patients with major extracardiac findings by computed tomography for attenuation correction.

BACKGROUND: Attenuation correction computed tomography (CT) contributes to an improvement in the diagnostic accuracy of myocardial perfusion imaging (MPI) by single photon emission tomography (SPECT). The aim of this study was to explore the prognosis of patients with major findings by CT according to the results of MPI. METHODS AND RESULTS: 1506 patients who underwent MPI by SPECT were retrospectively included. Attenuation correction CT images were systematically analyzed for major and minor abnormalities. 830 (55.1%) and 212 (14.1%) patients had minor and major extracardiac findings, respectively. Among patients with major extracardiac findings, the abnormality was previously unknown in 113 (53.3%) patients. 90 (41.9%) had abnormal MPI, 73 (34.4%) had a myocardial infarction scar, 55 (25.9%) had myocardial ischemia, and 38 (17.7%) patients had both myocardial infarction scar and myocardial ischemia. Among the 201 patients available for survival analysis, there were 67 (31.2%) deaths over a follow-up period of 3.2±1.3 years. There was no significant impact on survival arising from MPI, whatever the result. The results were the same among the 103 patients with previously unknown major extracardiac findings. CONCLUSION: Extracardiac findings by CT during MPI are frequent. Patients with major extracardiac findings have a poor mid-term outcome, whatever the results of the myocardial perfusion imaging. Extracardiac findings should be systematically checked when attenuation correction CT is performed.

Feasibility and accuracy of gated blood pool SPECT equilibrium radionuclide ventriculography for the assessment of left and right ventricular volumes and function in patients with left ventricular assist devices.

BACKGROUND: Left ventricular assist devices (LVADs) require serial assessment of right and left ventricular (RV & LV) volumes and function. Because the RV is not assisted, its function is a critical determinant of the hemodynamic and contributes significantly to postoperative morbidity and mortality. We evaluated the feasibility and the accuracy of tomographic-equilibrium radionuclide ventriculography (t-ERV) for the assessment of patients with LVADs. METHODS: Twenty-four patients with LVAD underwent t-ERV. Because of the limited acoustic window, transthoracic echocardiography (TTE) was only feasible in 19 patients. Functional evaluation including six-minute walk test (6MWT) and peak oxygen consumption (POC) was performed in 18 patients. Nine patients underwent a cardiac multidetector computed tomography (MDCT). Eight patients underwent a second evaluation by ERV 4.3 ± 1.4 months later. RESULTS: Reliability between t-ERV and MDCT for LV end-diastolic volume, LV end-systolic volume, LV ejection fraction, RV end-diastolic volume, RV end-systolic volume, and RV ejection fraction (RVEF) was 0.900 (P = .001), 0.911 (P = .001), 0.765 (P = .021), 0.728 (P = .042), 0.875 (P = .004), and 0.781 (P = .023), respectively. There was no correlation between t-ERV and RV systolic parameters assessed by TTE. RVEF was correlated with POC (R = 0.521; P = .027). A cut-off value of 40% for RVEF measured by t-ERV could discriminate patients with poor functional status (P = .048 for NYHA stage; P = .016 for 6MWT and P = .007 for POC). CONCLUSION: t-ERV is a simple, reproducible, and an accurate technique for the assessment of RV function in patients with LVADs and warrants consideration in the evaluation and monitoring of symptomatic patients.

Myocardial multilayer strain does not provide additional value for detection of myocardial viability assessed by SPECT imaging over and beyond standard strain.

BACKGROUND: The aim of this study was to evaluate the value of multilayer strain analysis to the assessment of myocardial viability (MV) through the comparison of both speckle tracking echocardiography and single-photon emission computed tomography (SPECT) imaging. We also intended to determine which segmental longitudinal strain (LS) cutoff value would be optimal to discriminate viable myocardium. METHODS: We included 47 patients (average age: 61 ± 11 years) referred to our cardiac imaging center for MV evaluation. All patients underwent transthoracic echocardiography with measures of LS, SPECT, and coronary angiography. RESULTS: In all, 799 segments were analyzed. We correlated myocardial tracer uptake by SPECT with sub-endocardial, sub-epicardial, and mid-segmental LS values with r = .514 P < .0001, r = .501 P < .0001, and r = .520 P < .0001, respectively. The measurements of each layer strain (sub-endocardial, sub-epicardial, and mid) had the same performance to predict MV viability as defined by SPECT with areas under curve of 0.819 [0.778-0.861, P < .0001], 0.809 [0.764-0.854, P < .0001], and 0.817 [0.773-0.860, P < .0001], respectively. The receiver-operating characteristic analysis yielded a cutoff value of -6.5% for mid-segmental LS with a sensitivity of 76% and specificity of 76% to predict segmental MV as defined by SPECT. CONCLUSIONS: Multilayer strain analysis does not evaluate MV with more accuracy than standard segmental LS analysis.

Serum allantoin and aminothiols as biomarkers of chronic heart failure.

Background Oxidative stress (OS) represents the primary mediator of chronic heart failure (CHF) development and progression. It is well established that homocysteine is able to generate reactive oxygen species. Small amounts of allantoin in human serum result from free radical action on urate and may provide a stable marker for in vivo free radical activity. To investigate whether some easily measurable indexes such as antioxidants (uric acid, glutathione) and related molecules (allantoin, homocysteine and cysteine) can serve as OS biomarkers. Methods We investigated 75 stable CHF patients. Aminothiols and purine compound levels were determined by capillary electrophoresis. Results The homocysteine level was markedly elevated in CHF patients, whatever the aetiology. Parameters of the transsulfuration pathway and the investigated purine compounds were significantly increased. Conversely, total glutathione was decreased. The allantoin/uric acid ratio was significantly higher in CHF patients with an hyperhomocysteinaemia >17 µmol/L. All parameters of the transsulfuration and purine degadation pathways were significantly correlated, suggesting an OS in CHF patients. Conclusion Our data show an imbalance of serum aminothiols and purine compounds in these CHF patients on adapted therapy. We suggest that the evaluation and control of these new markers may help improve the OS that participates in the progression of the disease.

X-Tream quality assurance in synchrotron X-ray microbeam radiation therapy.

Microbeam radiation therapy (MRT) is a novel irradiation technique for brain tumours treatment currently under development at the European Synchrotron Radiation Facility in Grenoble, France. The technique is based on the spatial fractionation of a highly brilliant synchrotron X-ray beam into an array of microbeams using a multi-slit collimator (MSC). After promising pre-clinical results, veterinary trials have recently commenced requiring the need for dedicated quality assurance (QA) procedures. The quality of MRT treatment demands reproducible and precise spatial fractionation of the incoming synchrotron beam. The intensity profile of the microbeams must also be quickly and quantitatively characterized prior to each treatment for comparison with that used for input to the dose-planning calculations. The Centre for Medical Radiation Physics (University of Wollongong, Australia) has developed an X-ray treatment monitoring system (X-Tream) which incorporates a high-spatial-resolution silicon strip detector (SSD) specifically designed for MRT. In-air measurements of the horizontal profile of the intrinsic microbeam X-ray field in order to determine the relative intensity of each microbeam are presented, and the alignment of the MSC is also assessed. The results show that the SSD is able to resolve individual microbeams which therefore provides invaluable QA of the horizontal field size and microbeam number and shape. They also demonstrate that the SSD used in the X-Tream system is very sensitive to any small misalignment of the MSC. In order to allow as rapid QA as possible, a fast alignment procedure of the SSD based on X-ray imaging with a low-intensity low-energy beam has been developed and is presented in this publication.

Energy spectra considerations for synchrotron radiotherapy trials on the ID17 bio-medical beamline at the European Synchrotron Radiation Facility.

The aim of this study was to validate the kilovoltage X-ray energy spectrum on the ID17 beamline at the European Synchrotron Radiation Facility (ESRF). The purpose of such validation was to provide an accurate energy spectrum as the input to a computerized treatment planning system, which will be used in synchrotron microbeam radiotherapy trials at the ESRF. Calculated and measured energy spectra on ID17 have been reported previously but recent additions and safety modifications to the beamline for veterinary trials warranted a fresh investigation. The authors used an established methodology to compare X-ray attenuation measurements in copper sheets (referred to as half value layer measurements in the radiotherapy field) with the predictions of a theoretical model. A cylindrical ionization chamber in air was used to record the relative attenuation of the X-ray beam intensity by increasing thicknesses of high-purity copper sheets. The authors measured the half value layers in copper for two beamline configurations, which corresponded to differing spectral conditions. The authors obtained good agreement between the measured and predicted half value layers for the two beamline configurations. The measured first half value layer was 1.754 ± 0.035 mm Cu and 1.962 ± 0.039 mm Cu for the two spectral conditions, compared with theoretical predictions of 1.763 ± 0.039 mm Cu and 1.984 ± 0.044 mm Cu, respectively. The calculated mean energies for the two conditions were 105 keV and 110 keV and there was not a substantial difference in the calculated percentage depth dose curves in water between the different spectral conditions. The authors observed a difference between their calculated energy spectra and the spectra previously reported by other authors, particularly at energies greater than 100 keV. The validation of the beam spectrum by the copper half value layer measurements means the authors can provide an accurate spectrum as an input to a treatment planning system for the forthcoming veterinary trials of microbeam radiotherapy to spontaneous tumours in cats and dogs.

Homocysteine in Chronic Heart Failure.

BACKGROUND: Hyperhomocysteinemia (HHcy) is a risk factor for cardiovascular disease. Homocysteine (Hcy) can generate reactive oxygen species. Oxidative stress enhances the progression of cardiovascular diseases and has long been implicated in chronic heart failure (CHF). This study was to evaluate the predictive value of plasma Hcy levels in CHF patients and to investigate the relationship with other markers. METHODS: We investigated 134 adult CHF patients (males, 74%; mean age, 60.0 ± 14.8 years). Echocardiography, 6-min walk test, and determination of peak oxygen consumption (VO(2max)) were performed. Serum levels of Hcy and other markers were determined. Clinical follow-up was performed at five years. RESULTS: The mean Hcy level was markedly elevated in CHF patients (18.4 ± 7.83 µmol/L) vs. control subjects (12.8 ± 3.14 µmol/L; p < 0.01), whatever the etiology of heart failure (non-ischemic, n = 74, 17.6 ± 7.8 µmol/L; ischemic, n = 60, 19.3 ± 7.8 µmol/L). Hcy correlated negatively with VO(2max) and positively with BNP. Kaplan-Meier analysis showed that CHF patients with HHcy > 15 µmol/L had a significantly lower survival rate (35% vs. 56%, log-rank p < 0.05) than those without HHcy. Cox regression revealed that HHcy and hs-CRP were the most powerful independent predictors of mortality in patients at 5 years. CONCLUSIONS: HHcy is common in CHF patients and is associated with an increased risk of death at 5 years. We suggest that Hcy can be used in clinical practice as an additional risk marker in CHF patients with various medications.

Benchmarking and validation of a Geant4-SHADOW Monte Carlo simulation for dose calculations in microbeam radiation therapy.

Microbeam radiation therapy (MRT) is a synchrotron-based radiotherapy modality that uses high-intensity beams of spatially fractionated radiation to treat tumours. The rapid evolution of MRT towards clinical trials demands accurate treatment planning systems (TPS), as well as independent tools for the verification of TPS calculated dose distributions in order to ensure patient safety and treatment efficacy. Monte Carlo computer simulation represents the most accurate method of dose calculation in patient geometries and is best suited for the purpose of TPS verification. A Monte Carlo model of the ID17 biomedical beamline at the European Synchrotron Radiation Facility has been developed, including recent modifications, using the Geant4 Monte Carlo toolkit interfaced with the SHADOW X-ray optics and ray-tracing libraries. The code was benchmarked by simulating dose profiles in water-equivalent phantoms subject to irradiation by broad-beam (without spatial fractionation) and microbeam (with spatial fractionation) fields, and comparing against those calculated with a previous model of the beamline developed using the PENELOPE code. Validation against additional experimental dose profiles in water-equivalent phantoms subject to broad-beam irradiation was also performed. Good agreement between codes was observed, with the exception of out-of-field doses and toward the field edge for larger field sizes. Microbeam results showed good agreement between both codes and experimental results within uncertainties. Results of the experimental validation showed agreement for different beamline configurations. The asymmetry in the out-of-field dose profiles due to polarization effects was also investigated, yielding important information for the treatment planning process in MRT. This work represents an important step in the development of a Monte Carlo-based independent verification tool for treatment planning in MRT.

Towards etiological treatments in cardiomyopathies.

This review proposes to look at the evolution of cardiomyopathy treatments in the light of advances in diagnostic techniques, which have enabled to move from a mechanistic to a phenotypic and then etiological approach. The article goes beyond the ejection fraction approach, and look at new therapies that target the pathophysiological pathways of cardiomyopathies, either by targeting the phenotype, or by targeting the etiology. The evolution of HCM treatments is detailed, culminating in the latest etiological treatments such as mavacamten in sarcomeric HCM, tafamidis in transthyretin cardiac amyloidosis and migalastat in Fabry disease. Myosin stimulators are reviewed in the treatment of DCM, before opening perspectives for gene therapy, which proposes direct treatment of the culprit mutation.

[Optimizing the management of heart failure: structuring the care pathway]. / Optimisation de la prise en charge de l'insuffisance cardiaque : structuration du parcours de soins.

The incidence of chronic heart failure continues to rise in Western countries, justifying the implementation of an optimized multidisciplinary organization based on medical and nursing convergence. Around the main heart failure, assistance and transplantation unit at Toulouse University Hospital, several structures have been put in place to better manage heart failure patients and improve their care pathway.

Prevalence, clinical significance and prognosis value of liver stiffness measurement anomalies in transthyretin cardiac amyloidosis.

Background - Laboratory liver anomalies are common in cardiac amyloidosis; however, their significance regarding liver stiffness is unknown. The aim of this study was to investigate the prevalence, clinical significance, and prognostic value of liver stiffness measurement (LSM) anomalies in transthyretin cardiac amyloidosis (ATTR-CA). Methods - Consecutive patients diagnosed with ATTR-CA who underwent liver stiffness assessment were included in the study. Demographic, clinical, laboratory, transthoracic echocardiography and liver stiffness data were retrospectively collected. LSM was obtained through either transient elastography or supersonic shear imaging. Patient cohort was divided in two groups according to a 10 kPa threshold. Follow up data were collected for the occurrence of hospitalization for heart failure and all-cause death. Results - Two hundred and eighty-four patients with ATTR-CA - 26 (9 %) hereditary variant ATTR, 258 (91 %) wild-type ATTR - were included. A LSM over 10 kPa was found in 4 (15 %) and 98 (38 %) patients with ATTRv and ATTRwt respectively (p = 0.02). Among patients with ATTRwt, high LSM was more frequent in advanced stages of ATTR-CA and was associated with increased risk of hospitalization for heart failure after multivariate analysis with a hazard ratio of 2.41 [1.05-5.55] (p = 0.04). Among patients with NYHA stage 1, 28 % presented high LSM associated with high NT-proBNP levels. Integration of high LSM with NT-proBNP and estimated glomerular filtration rate provided a better estimate of patient survival. Conclusion - LSM over 10 kPa is found in up to 36 % of patients with ATTR-CA and is associated with advanced stages of cardiomyopathy and increased risk of hospitalization for heart failure in ATTRwt patients.

Descriptive study of the clinical and myocardial status of a population with anatomopathological aortic valve amyloidosis.

BACKGROUND: Aortic stenosis (AS) and transthyretin (ATTR) cardiac amyloidosis (CA) share the same clinical profiles and cardiac phenotype. Amyloid deposits have been frequently reported in aortic valves of patients with severe AS referred for surgical aortic valve replacement (SAVR). The aim of this study was to determine the clinical and myocardial status of patients with aortic valve amyloidosis after aortic valve surgery. METHODS AND RESULTS: We performed a retrospective descriptive study of 46 patients who underwent SAVR for severe AS with amyloid deposits upon histological analysis. All patients were screened for cardiac involvement. Amyloid deposits typing was successful in 35 (76%) patients and 28 (80%) were ATTR. Two (4%) had positive bone scintigraphy and among the 5 myocardial biopsies performed during surgery, 80% were positive for ATTR deposits. CONCLUSION: ATTR is the predominant type in the presence of amyloid deposits on the aortic valve after surgery for severe AS but is only rarely accompanied by cardiac uptake on bone scintigraphy. Early stages of myocardial involvement are frequent and myocardial biopsy is more sensitive for detection of mild amyloid deposits than bone scintigraphy.