Transthyretin amyloid polyneuropathy in France: A cross-sectional study with 413 patients and real-world tafamidis meglumine use (2009-2019).

OBJECTIVE: We aimed to describe characteristics of patients with ATTR variant polyneuropathy (ATTRv-PN) and ATTRv-mixed and assess the real-world use and safety profile of tafamidis meglumine 20mg. METHODS: Thirty-eight French hospitals were invited. Patient files were reviewed to identify clinical manifestations, diagnostic methods, and treatment compliance. RESULTS: Four hundred and thirteen patients (296 ATTRv-PN, 117 ATTRv-mixed) were analyzed. Patients were predominantly male (68.0%) with a mean age of 57.2±17.2 years. Interval between first symptom(s) and diagnosis was 3.4±4.3 years. First symptoms included sensory complaints (85.9%), dysautonomia (38.5%), motor deficits (26.4%), carpal tunnel syndrome (31.5%), shortness of breath (13.3%), and unexplained weight loss (16.0%). Mini-invasive accessory salivary gland or punch skin and nerve biopsies were most common, with a performance of 78.8-100%. TTR genetic sequencing, performed in all patients, revealed 31 TTR variants. Tafamidis meglumine was initiated in 156/214 (72.9%) ATTRv-PN patients at an early disease stage. Median treatment duration was 6.00 years in ATTRv-PN and 3.42 years in ATTRv-mixed patients. Tafamidis was well tolerated, with 20 adverse events likely related to study drug among the 336 patients. CONCLUSION: In France, ATTRv patients are usually identified early thanks to the national network and the help of diagnosis combining genetic testing and mini-invasive biopsies.

EACVI survey on radiation exposure in interventional echocardiography.

AIMS: The European Association of Cardiovascular Imaging (EACVI) Scientific Initiatives Committee performed a global survey on radiation exposure in interventional echocardiography. The survey aimed to collect data on local practices for radioprotection in interventional echocardiography and to assess the awareness of echocardiography operators about radiation-related risks. METHODS AND RESULTS: A total of 258 interventional echocardiographers from 52 different countries (48% European) responded to the survey. One hundred twenty-two (47%) participants were women. Two-thirds (76%) of interventional echocardiographers worked in tertiary care/university hospitals. Interventional echocardiography was the main clinical activity for 34% of the survey participants. The median time spent in the cath-lab for the echocardiographic monitoring of structural heart procedures was 10 (5-20) hours/month. Despite this, only 28% of interventional echocardiographers received periodic training and certification in radioprotection and 72% of them did not know their annual radiation dose. The main adopted personal protection devices were lead aprons and thyroid collars (95% and 92% of use, respectively). Dedicated architectural protective shielding was not available for 33% of interventional echocardiographers. Nearly two-thirds of responders thought that the radiation exposure of interventional echocardiographers was higher than that of interventional cardiologists and 72% claimed for an improvement in the radioprotection measures. CONCLUSION: Radioprotection measures for interventional echocardiographers are widely variable across centres. Radioprotection devices are often underused by interventional echocardiographers, portending an increased radiation-related risk. International scientific societies working in the field should collaborate to endorse radioprotection training, promote reliable radiation dose assessment, and support the adoption of radioprotection shielding dedicated to interventional echocardiographers.

Cardiovascular magnetic resonance in autoimmune rheumatic diseases: a clinical consensus document by the European Association of Cardiovascular Imaging.

Autoimmune rheumatic diseases (ARDs) involve multiple organs including the heart and vasculature. Despite novel treatments, patients with ARDs still experience a reduced life expectancy, partly caused by the higher prevalence of cardiovascular disease (CVD). This includes CV inflammation, rhythm disturbances, perfusion abnormalities (ischaemia/infarction), dysregulation of vasoreactivity, myocardial fibrosis, coagulation abnormalities, pulmonary hypertension, valvular disease, and side-effects of immunomodulatory therapy. Currently, the evaluation of CV involvement in patients with ARDs is based on the assessment of cardiac symptoms, coupled with electrocardiography, blood testing, and echocardiography. However, CVD may not become overt until late in the course of the disease, thus potentially limiting the therapeutic window for intervention. More recently, cardiovascular magnetic resonance (CMR) has allowed for the early identification of pathophysiologic structural/functional alterations that take place before the onset of clinically overt CVD. CMR allows for detailed evaluation of biventricular function together with tissue characterization of vessels/myocardium in the same examination, yielding a reliable assessment of disease activity that might not be mirrored by blood biomarkers and other imaging modalities. Therefore, CMR provides diagnostic information that enables timely clinical decision-making and facilitates the tailoring of treatment to individual patients. Here we review the role of CMR in the early and accurate diagnosis of CVD in patients with ARDs compared with other non-invasive imaging modalities. Furthermore, we present a consensus-based decision algorithm for when a CMR study could be considered in patients with ARDs, together with a standardized study protocol. Lastly, we discuss the clinical implications of findings from a CMR examination.

Prognostic utility of the assessment of diastolic function in patients undergoing cardiac resynchronization therapy.

Conflicting data exist about the relationship between cardiac resynchronization therapy (CRT) and diastolic function. Aims of the study are to assess diastolic patterns in patients undergoing CRT according to the 2016 recommendations of the American Society of Echocardiography/European Association of Cardiovascular Imaging and to evaluate the prognostic value of diastolic dysfunction (DD) in CRT candidates. METHODS AND RESULTS: One-hundred ninety-three patients (age: 67 ± 11 years, QRS width: 167 ± 21 ms) were included in this multicentre prospective study. Mitral filling pattern, mitral tissue Doppler velocity, tricuspid regurgitation velocity, and indexed left atrial volume were used to classify DD from grade I to III. CRT-response, defined as a reduction of left ventricular (LV) end-systolic volume > 15% at 6-month follow-up (FU), occurred in 132 (68%) patients. The primary endpoint was a composite of heart transplantation, LV assisted device implantation, or all-cause death during FU and occurred in 29 (15%) patients. CRT was associated with a degradation of DD in non-responders. At multivariable analysis corrected for clinical variables, QRS duration, mitral regurgitation, CRT-response and LV dyssynchrony, grade I DD was associated with a better outcome (HR 0.37, 95% CI: 0.14-0.96). Non-responders with grade II-III DD had the worse prognosis (HR 4.36, 95%CI: 2.10-9.06). CONCLUSIONS: The evaluation of DD in CRT candidates allows the prognostic stratification of patients, independently from CRT-response.

[Non-infective endocarditis]. / Les endocardites non infectieuses.

Non-infective endocarditis, also referred to as non-bacterial thrombotic endocarditis, represent a wide range of rare pathologies, often severe. This review gathered the data available in the literature, to decipher the major information collected on the pathophysiology, the diagnosis and the treatment of these heterogeneous diseases, often misdiagnosed. Characteristics of non-infective endocarditis are similar to infective endocarditis in terms of valvular lesions (mostly left-sided, with regurgitations and vegetations), and their complications (embolism). The diagnosis of non-infective endocarditis is usually considered in patients with blood culture-negative endocarditis. Beyond the usual suspects - marastic endocarditis and systemic lupus erythematosus - which represent more than 75% of the cases, Behçet disease and hypereosinophilic syndrome are the main causes of non-infective endocarditis. More seldomly, rheumatoid arthritis, adult-onset Still disease, allergy to pork in patients with valvular procine bioprosthesis, systemic scleroderma, Cogan or Sneddon syndrome should be suspected. Diagnostic approach is based on history and physical examination, with a special focus on extra-cardiac manifestations, as well as echocardiography, and computed tomography. Treatment relies on intensive management of the underlying disease. Curative anticoagulation is often necessary. Although indications for cardiac surgery are poorly defined, as compared to infective endocarditis, data currently available suggest that an optimal control of the underlying disease before cardiac surgery is of utmost importance, as it dramatically reduces the risk of postoperative complications.

Left atrial rather than left ventricular impaired mechanics are associated with the pro-fibrotic ST2 marker and outcomes in heart failure with preserved ejection fraction.

AIMS: Left ventricular (LV) mechanics have been extensively investigated in heart failure with preserved ejection fraction (HFpEF) overshadowing for a long time the potential role of left atrium (LA) in that setting. Soluble suppression of tumorigenicity-2 receptor (ST2) is a novel biomarker of pro-fibrotic burden in HF. We hypothesized that due to the thinner LA wall, the fibrotic myocardial changes in HFpEF as indicated by elevated ST2 levels might more readily be reflected by impairments in the LA rather than the LV performance. METHODS AND RESULTS: In 86 patients with HFpEF, enrolled in the Karolinska Rennes (KaRen) biomarker prospective substudy, global LA strain (GL-LS) along with other echocardiographic as well as haemodynamic parameters and ST2 levels were measured. ST2 levels were inversely associated with LA-GS (r = -0.30, P = 0.009), but not with LA size, LV geometry, systolic or diastolic LV function (P > 0.05 for all). Furthermore, symptom severity correlated with ST2 and LA-GS, but not with LV structural or functional indices. Finally, during a median 18-month follow-up, LA-GS independently predicted the composite endpoint of HF hospitalization and all-cause mortality, even after adjustment for potential clinical and cardiac mechanical confounders, including LV global longitudinal strain and filling pressures (odds ratio: 4.15; confidence interval: 1.2-14, P = 0.023). CONCLUSIONS: Reduced LA-GS but not LV functional systolic and diastolic parameters were associated with the pro-fibrotic ST2 marker, HF symptoms and outcome in HFpEF.

Multiple Behavior Descriptions Affect the Acquisitions of STI and STT.

Four studies pursued the idea that spontaneous trait inferences (STIs) involve the formation of both inferential knowledge and associative knowledge while spontaneous trait transferences (STTs) involve only the formation of associative knowledge. These studies varied the type and amount of behavioral information from which perceivers could extract trait information. Experiments 1a and 1b used a modified savings-in-relearning paradigm and demonstrated that repeated presentations of an individual and a behavior description increased the strength of association between the target and implied trait, and this effect did not depend on whether the repeated presentations involved redundant information or new information. In comparison, Experiments 2a and 2b used a trait ratings dependent variable and demonstrated that the effects of repetition were stronger for STI, but not STT, when the added information differed from information that was previously encountered, but not when it was redundant with the previously encountered information.

Prognostic value of left atrial reservoir function in patients with severe aortic stenosis: a 2D speckle-tracking echocardiographic study.

AIMS: The aim of this article is to assess the left atrial (LA) reservoir function in patients with severe aortic stenosis (AS) and to evaluate its impact on the recurrence of major adverse cardiac events (MACEs). METHODS AND RESULTS: About 128 patients (mean age 79 ± 9 years) with severe AS were included in the study. Global peak LA strain (PLAS) measured by two-dimensional speckle-tracking echocardiography (STE) during left ventricular (LV) systole represented the LA reservoir function. Overall death, hospitalization for cardiac cause, and worsening heart failure were defined as MACEs. With respect to the values observed in a control group of 20 healthy patients, PLAS resulted significantly reduced in AS. According to the multivariate linear regression analysis, LV global longitudinal strain, mitral E/e' ratio, and systolic pulmonary arterial pressure (sPAP) were the best correlates to PLAS. During follow-up, the predefined MACEs occurred in 39 patients. According to the multivariate Cox regression analysis, a PLAS <21% was a significant predictor of MACEs [hazard ratio (HR) 2.88, P = 0.04], as was coronary artery disease (HR 2.68, P = 0.004) and the New York Heart Association functional class (HR 2.08, P = 0.03). CONCLUSION: In patients with severe AS, a global PLAS <21% is an independent predictor of prognosis. Given the combined influence of LV diastolic and systolic function and of LA performance on sPAP, the decline of PLAS might be considered a marker of global myocardial impairment in AS. Further studies are needed to confirm the critical role of LA relaxation in prognosis and to validate its relevance in routine clinical practice.

P697New indices for a best quantification of left ventricular function in heart valve diseases.

Aims.The Assessment of left ventricular (LV) function remains a clinical challenge especially in patients with preserved LV ejection fraction (EF) and valvular heart diseases (VHD). Mechanical dispersion is supposed to be a strong predictor of events and, to be related to the extent of fibrosis. Regional cardiac work is a new validated and very promising approach to quantify LV-function.We investigated the differences in mechanical dispersions and global LV work (totW) and wasted work fraction (WWF) in normal subjects and in patients with severe primary mitral regurgitation (MR) and severe aortic stenosis (AS). METHODS AND RESULTS: A complete transthoracic echocardiography was performed in 21 normal subject, 97 patients with severe valvulopathy (47 AS, 50 MR) and preserved LV EF. Segmental strain analysis was performed in all patients and the dispersion of regional LV strain curves was computed automatically considering peaks and integrals. The LV-pressure was estimated non-invasively using a standard waveform fitted to valvular events and scaled to systolic blood pressure. Using pressure-strain loops, regional cardiac work indices were computed.LVEF was 66±12 in controls, 65±9 in MR and 65±4% in AS (p=0.125). Global longitudinal strain was -23±2.7 in controls, -24±2.9 in MR and -18±3.2% in AS (p < 0.001). The mechanical dispersion was 38±7.9 in controls, 36±11 in MR, and much higher in the hypertrophied LV of the AS: 60±19ms (p < 0.001). Cardiac work was 2200±260 in controls, 2100±270 in MR, and much lower in AS: 1700±280 mmHg.% (p < 0.001). The wasted work fraction (WWF) was even more describing how different the LV systolic function is in the 3 groups (figure1). CONCLUSION: Longitudinal strain data are robusted and new indices might be calculated based on them. These seem especially promising for a more pathophysiological driven analyzing of LV-functions. Abstract P697 Figure.Abstract P697 Figure.

Spontaneous evaluative inferences and their relationship to spontaneous trait inferences.

Three experiments are reported that explore affectively based spontaneous evaluative impressions (SEIs) of stimulus persons. Experiments 1 and 2 used modified versions of the savings in relearning paradigm (Carlston & Skowronski, 1994) to confirm the occurrence of SEIs, indicating that they are equivalent whether participants are instructed to form trait impressions, evaluative impressions, or neither. These experiments also show that SEIs occur independently of explicit recall for the trait implications of the stimuli. Experiment 3 provides a single dissociation test to distinguish SEIs from spontaneous trait inferences (STIs), showing that disrupting cognitive processing interferes with a trait-based prediction task that presumably reflects STIs, but not with an affectively based social approach task that presumably reflects SEIs. Implications of these findings for the potential independence of spontaneous trait and evaluative inferences, as well as limitations and important steps for future study are discussed.

Outpatient parenteral antimicrobial therapy for infective endocarditis: a cost-effective strategy.

OBJECTIVES: We evaluated the benefit/risk ratio of outpatient parenteral antimicrobial therapy (OPAT) in infective endocarditis (IE). METHOD: We performed an observational retrospective study of definite IE (Duke criteria) treated in an infectious diseases unit in 2012. We compared patients having completed the treatment in hospital (H), and those deemed sufficiently stable, and with adequate home environment, for OPAT. The costs were estimated through hospital bills, and, for OPAT, through the costs of drugs and their administration (material, staff), transportation, and outpatient visits. RESULTS: Eighteen out of 39 consecutive patients presenting with IE received OPAT, with a mean hospital stay of 23.5days (vs 34.7days for H group, P=0.014). No severe adverse event related to OPAT was reported. The global saving was estimated at 267,307euros, or 14,850euros per patient. CONCLUSIONS: OPAT in selected patients presenting with IE seems effective, safe, and reduces costs by approximately 15,000euros per patient.

Personalization of a cardiac electromechanical model using reduced order unscented Kalman filtering from regional volumes.

Patient-specific cardiac modeling can help in understanding pathophysiology and therapy planning. However it requires to combine functional and anatomical data in order to build accurate models and to personalize the model geometry, kinematics, electrophysiology and mechanics. Personalizing the electromechanical coupling from medical images is a challenging task. We use the Bestel-Clément-Sorine (BCS) electromechanical model of the heart, which provides reasonable accuracy with a reasonable number of parameters (14 for each ventricle) compared to the available clinical data at the organ level. We propose a personalization strategy from cine MRI data in two steps. We first estimate global parameters with an automatic calibration algorithm based on the Unscented Transform which allows to initialize the parameters while matching the volume and pressure curves. In a second step we locally personalize the contractilities of all AHA (American Heart Association) zones of the left ventricle using the reduced order unscented Kalman filtering on Regional Volumes. This personalization strategy was validated synthetically and tested successfully on eight healthy and three pathological cases.

Understanding the mechanisms amenable to CRT response: from pre-operative multimodal image data to patient-specific computational models.

This manuscript describes our recent developments towards better understanding of the mechanisms amenable to cardiac resynchronization therapy response. We report the results from a full multimodal dataset corresponding to eight patients from the euHeart project. The datasets include echocardiography, MRI and electrophysiological studies. We investigate two aspects. The first one focuses on pre-operative multimodal image data. From 2D echocardiography and 3D tagged MRI images, we compute atlas based dyssynchrony indices. We complement these indices with presence and extent of scar tissue and correlate them with CRT response. The second one focuses on computational models. We use pre-operative imaging to generate a patient-specific computational model. We show results of a fully automatic personalized electromechanical simulation. By case-per-case discussion of the results, we highlight the potential and key issues of this multimodal pipeline for the understanding of the mechanisms of CRT response and a better patient selection.

Optimal algorithm switching for the estimation of systole period from cardiac microacceleration signals (SonR).

Previous studies have shown that cardiac microacceleration signals, recorded either cutaneously, or embedded into the tip of an endocardial pacing lead, provide meaningful information to characterize the cardiac mechanical function. This information may be useful to personalize and optimize the cardiac resynchronization therapy, delivered by a biventricular pacemaker, for patients suffering from chronic heart failure (HF). This paper focuses on the improvement of a previously proposed method for the estimation of the systole period from a signal acquired with a cardiac microaccelerometer (SonR sensor, Sorin CRM SAS, France). We propose an optimal algorithm switching approach, to dynamically select the best configuration of the estimation method, as a function of different control variables, such as the signal-to-noise ratio or heart rate. This method was evaluated on a database containing recordings from 31 patients suffering from chronic HF and implanted with a biventricular pacemaker, for which various cardiac pacing configurations were tested. Ultrasound measurements of the systole period were used as a reference and the improved method was compared with the original estimator. A reduction of 11% on the absolute estimation error was obtained for the systole period with the proposed algorithm switching approach.

Imaging and modern assessment of the right ventricle.

The right ventricular function is difficult to assess owing to its complex morphology, structure and function. The right ventricle (RV) comprises three compartments, the inlet, the apex, and the outlet contracting with a peristaltic motion from the inflow to the outflow chamber and is tightly linked to left ventricular (LV) function through the pulmonary circulation, the interventricular septum and the myocardium inside the pericardial envelop. The relation of RV function to symptom occurrence, exercise capacity and prognosis in a wide variety of cardiac diseases emphasizes the usefulness of its routine assessment. The evaluation of the RV is largely carried out by echocardiography in daily clinical practice despite important limitations inherent to two-dimensional imaging. Multiple views and numerous parameters allow clinicians to integrate the RV function in the clinical decision-making process. Recent modalities of echocardiography such as myocardial deformation and three-dimensional imaging or exercise echocardiography are promising tools for the assessment of the RV. Cardiac magnetic resonance imaging provides the unique opportunity to image the RV in motion and in three dimensions without the limitation of echogenicity. Therefore, cardiac magnetic resonance imaging is taking a growing place in the assessment of the RV in a wide variety of cardio-pulmonary diseases as pulmonary hypertension, ischemia, arrhythmogenic right ventricular cardiomyopathy, hypertrophic cardiomyopathy, heart failure or congenital heart diseases. Integrating the complex interplay between both ventricles and the pulmonary circulation, this review will discuss the latest results of standard and novel techniques allowing the assessment of RV function by echocardiography and cardiac magnetic resonance imaging, and will provide to the clinicians, facing therapeutic challenges, a comprehensive overview of right heart function.

Early and late cardiac ventricular reverse remodeling after catheter ablation for lone paroxysmal atrial fibrillation.

AIM: We sought to explore ventricular function in patients with lone paroxysmal atrial fibrillation (AF) and determine the mid- and long-term impact of pulmonary vein isolation on cardiac remodeling. BACKGROUND: The relationship between tachyarrhythmia and ventricular dysfunction is still a matter of debate. Tachycardia-induced cardiomyopathy is defined as reversible myocardial dysfunction following treatment for tachyarrhythmia. METHOD: We prospectively studied 31 patients (56.4 ± 10 years) presenting with paroxysmal-AF who were treated successfully by catheter ablation and 15 age-matched controls. Left and right ventricular functions were assessed by echocardiography at baseline and at 3-month and 1-year follow-up. RESULTS: In AF-patients, LV-function was slightly lower at baseline than controls (LV-ejection fraction was 60% versus 64%; P = 0.06). More impressive, systolic peak velocity on Doppler tissue imaging was 9 cm/s in AF patients (versus 12 cm/s; P = 0.0004). LV global longitudinal strain was also significantly different between the two groups (patients: -16% versus controls: -19%; P = 0.005). At 1-year follow-up, most functional parameters significantly improved in the AF-patients and no longer differed from the controls. Right ventricular (RV) function was also depressed in AF patients at baseline. At 1-year follow-up, tissue Doppler showed improvement in RV-S' (+27%, P = 0.007) and RV peak systolic strain (+36%, P<0.0001) and became comparable to controls. CONCLUSION: We demonstrate that some degree of arrhythmic cardiomyopathy exists in patients presenting with lone paroxysmal-AF. Catheter ablation improved RV and LV functions. Longitudinal function is the most sensitive component of ventricular systole to monitor when looking for this cardiac reverse remodeling.

Biological and hemodynamic effects of low doses of fludrocortisone and hydrocortisone, alone or in combination, in healthy volunteers with hypoaldosteronism.

Low doses of hydrocortisone (HC) and fludrocortisone (FC) administered together improve the prognosis after septic shock; however, there continues to be disagreement about the utility of FC for this indication. The biological and hemodynamic effects of HC (50 mg intravenously) and FC (50 microg orally) were assessed in 12 healthy male volunteers with saline-induced hypoaldosteronism in a placebo-controlled, randomized, double-blind, crossover study performed according to a 2 x 2 factorial design. HC and FC significantly decreased urinary sodium and potassium levels (from -58% at 4 h to -28% at 10 h and from -35% at 8 h to -24% at 12 h, respectively) with additive effects. At 4 h after administration, HC significantly increased cardiac output (+14%), decreased systemic vascular resistances (-14%), and slightly increased heart rate (+4 beats/min), whereas FC had no hemodynamic effect. At doses used in septic shock, HC induced greater mineralocorticoid effect than FC did. HC also induced transient systemic hemodynamic effects, whereas FC did not. New studies are required to better define the optimal dose of FC in septic shock.