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.

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.

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.

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.

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.

[Contribution of cardiac MRI in the etiologic diagnosis of chest pain syndrome with a normal angiographic aspect of the coronary arteries]. / Apport de l'IRM cardiaque dans le diagnostic étiologique des syndromes douloureux thoraciques à réseau coronaire angiographiquement normal.

The etiologic diagnosis of chest pain with elevation of specific cardiac enzymes, repolarization abnormalities and a normal angiographic aspect of the coronary arteries is difficult. In this situation, the role of cardiac MRI is growing, frequently allowing to precise the etiology of the chest pain. We present a literature review concerning the semiology of the cardiac MRI in the three main involved etiologies: myocarditis, takotsubo syndrome, and myocardial ischemia with a normal angiographic aspect of the coronary arteries.

[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.

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.

[The significance and development of quantitative study of the myocardium with echocardiography]. / Intérêt et développement de l'étude quantitative du myocarde en échocardiographie.

Quantification, standardisation, and reproducibilty are three of the constraints facing echocardiography. New MRI and CT techniques allow some of these constraints to be circumvented. Tissue Doppler, using a quantitative and very physiological approach in theory will enable echocardiographic evaluation to advance. A low reproducibilty for Doppler tools limits routine widespread use. This problem should in future be avoided by using a more recent and more exhaustive approach called 2D-strain, based on processing conventional images with a technique called 'speckle tracking'. These tools are still new, but without doubt they herald a new method which is both more pathophysiological and quantitative.

[Beta-blocker prescription and chronic obstructive pulmonary disease]. / Prescription des bêtabloquants et bronchopneumopathie chronique obstructive.

The beta-blocker (BB) prescription remains insufficient despite guidelines, especially, for chronic heart failure. Patients suffering chronic obstructive pulmonary disease (COPD) are particularly less treated by BB. The level of evidence for BB prescription is however especially high and as we will focus on, the level of evidence for the safety of BB in the COPD context is convincing enough. We, thus, propose to review the existing literature in regard to this prescription of BB in the chronic heart failure, in the coronary artery disease and for high blood pressure in COPD patients. We then propose our approach to improve the level of prescription of BB in COPD patient really justifying this prescription in cardiology.

[Ischemic mitral regurgitation: contributions of exercise echocardiography and new therapeutic perspectives]. / Insuffisance mitrale ischémique: apport de l'échocardiographie d'effort et nouvelles perspectives thérapeutiques.

The ischemic mitral regurgitation is defined by a left ventricular muscle disease affecting the function of normal mitral valve leaflets. This kind of mitral regurgitation is founded in about 20% of the ischemic cardiomyopathy and is attributed to the remodelling of the left ventricular shape. Its development is associated to a significantly worse prognosis. Frequently this ischemic mitral regurgitation will be associated to episode of acute heart failure decompensation. Its diagnosis is sometimes challenging as the degree of regurgitation might be extremely variable and affected by loading conditions. Echocardiography and especially exercise stress echocardiography has been demonstrated as an extremely powerful tool for its diagnosis and the prognostic evaluation. Its treatment should include the pharmacological treatment of the chonic heart failure and we are still waiting data in regard to the prognostic role of surgical mitral valvuloplastie. Works are still ongoing.

[Impact of the aetiology of cardiac failure on the correlations between electrical and mechanical asynchrony of the ventricle]. / Influence de l'étiologie de l'insuffisance cardiaque sur la corrélation entre asynchronismes électrique et mécanique dans le ventricule.

Cardiac resynchronisation therapy (CRT) is indicated in refractory cardiac failure with electrical asynchrony defined by QRS complexes > or =120 ms duration. The search for mechanical asynchrony is proposed for better selection of patients for CRT. Ischaemic and non-ischaemic cardiomyopathy do not necessarily show the same form of asynchrony. The authors studied the differences in correlation between electrical and mechanical asynchrony in these two patient populations. Fifty patients (34 dilated non-ischaemic and 16 ischaemic cardiomyopathy) in NYHA Classes III and IV, LVEF < 35%, consecutively implanted for CRT in 2004, were included. The trans-thoracic echocardiography, the ECG and clinical parameters (NYHA, 6 minute walk test, VO2 max) were compared. A non-significant improvement of the correlation between the aortic pre-ejection time and QRS duration was observed in the non-ischaemic group (r = 0.78, p< 0.0001) compared with the ischaemic cardiomyopathy group ( r = 0.56, p = 0.019). Similarly, intraventricular asynchrony seemed to be correlated with the duration of QRS in the non-ischaemic group (r = 0.65, p < 0.0001) unlike the ischaemic cardiomyopathy group (ns). Sub-group analysis of patients with QRS durations < 150 ms and > or =150 ms showed an electromechanical correlation irrespective of the QRS duration in the non-ischaemic group but this was only observed with the aortic pre-ejection time with QRS > or =150 ms in the ischaemic group. The authors conclude that there is a significant correlation between electrical and mechanical asynchrony in patients with non-ischaemic cardiomyopathy. This correlation only applies to intraventricular asynchrony with QRS durations > or =150 ms in the ischaemic group. A decision for CRT requires echocardiographic evaluation in ischaemic cardiomyopathy.

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.

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.

Contribution of head-up tilt testing and ATP testing in assessing the mechanisms of vasovagal syndrome: preliminary results and potential therapeutic implications.

BACKGROUND: In patients with vasovagal syndrome, head-up tilt testing may reproduce symptoms generally associated with vasodepression. Recent research suggests ATP testing identifies patients with abnormal vagal cardiac inhibition. This preliminary study examined the joint contribution of both tests in identifying underlying mechanisms in the general population with vasovagal syndrome. METHODS AND RESULTS: Both tests were performed in random order during 1 session and outside of predominant sympathetic periods in 72 patients hospitalized for syncope (n=56) or presyncope (n=16) for whom no cardiac or extracardiac cause was found. For passive and isoproterenol-provocative tilt testing by standard protocol, reproduction of symptoms defined a positive test. The ATP test consisted of injecting ATP 20 mg IV at bedside, continuously monitoring ECG and blood pressure; a vagal cardiac pause >10 seconds defined a positive test. For most patients (64%), >/=1 test was positive. Of the 41 patients (57%) with a positive tilt test (either passive or provoked by isoproterenol), 32% had cardiac disease; none had significant bradycardia (<50 bpm). Of the 8 patients (11%) with a positive ATP test, 62% had cardiac disease; the probability of a positive result increased with age (P=0.015). Both tests were positive in 3 patients and negative in 26 patients; the tilt and ATP test results were uncorrelated (P=0.28). CONCLUSIONS: Results suggest tilt and ATP tests individually and jointly determine the mechanism of vasovagal symptoms in most patients and that vagal cardiac inhibition increases with age.

Linking versus thinking: evidence for the different associative and attributional bases of spontaneous trait transference and spontaneous trait inference.

Informants who describe others' behaviors are perceived as having more of the trait implied by the behavior they describe (the trait transference effect). Associative and attributional explanations for this phenomenon are reviewed and examined in 3 experiments. Findings were inconsistent with attributional interpretations: (a) transference effects persisted with extended coding times, online judgments, and warnings to participants to avoid the effect; (b) negativity effects were absent in transference but occurred with trait inference; and (c) transference effects failed to generalize beyond the particular trait implied by informants' descriptions. Moreover, forcing participants to recall the target of informants' descriptions just prior to trait judgments eliminated the transference effect while enhancing inference effects. These results contradict nonassociative explanations and indicate that different processes underlie spontaneous trait transference and spontaneous trait inference.

[Atrial remodeling, systemic hypertension, stroke]. / Remodelage auriculaire, hypertension artérielle et risque cérébral.

Atrial remodeling has been demonstrated to be associated with rapid atrial pacing or with hemodynamic overload. It may refer to changes in electrophysiological properties and/or in structure and function. Hemodynamic overload of the atria has been found to be an important pathogenic factor of atrial fibrosis, providing a morphological substrate for atrial fibrillation. This finding could partly account for the high risk of stroke in hypertensive patients. In this respect, a strong involvement of the renin angiotensin system has been suggested by experimental, clinical and epidemiological data. Thus, prevention or even partial regression of atrial remodeling could be reasonably expected from ACE-inhibitors and angiotensin 2-blockers.

[Viral cardiomyopathy]. / Cardiomyopathies virales. A propos de 4 observations d'infection myocardique à parvovirus B-19 et revue de la littérature.

In too many cases, the cause of dilated cardiomyopathy (DCM) remains undetermined. Coronary or valvular heart diseases, connective tissue disorders, toxic causes and signs of infection are systematically investigated. With the exceptions of coronary and sometimes valvular heart disease, the treatment of cardiac failure remains symptomatic treating the consequences but not the cause of DCM, which is therefore diagnosed as "idiopathic". This artericle reports the clinical history of 4 patients followed up for apparently "idiopathic" DCM in whom the presence of chronic Parvovirus B-19 infection was demonstrated. Based on these 4 cases, the hypothesis of an infectious cause of DCM and the role of myocardial biopsy, given the progress in molecular biology, are reconsidered. Parvovirus B-19 infection has recently been recognised not only as a cause of myocarditis but also of chronic viral cardiomyopathy, as in adeno and enteroviral infection. The authors conclude that the progress in molecular biology, the recognition of a viral aetiology and the efficacy of immuno-modulator therapy such as beta-interferon, may lead to a new management strategy of patients with DCM in cardiological referral centres.