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Aims Cardiac amyloidosis (CA) has a poor prognosis which is aggravated by diagnostic delay. Amyloidosis extracardiac and cardiac events (AECE and ACE) may help improve CA diagnosis and typing. The aim of this study was to compare AECE and ACE between different CA types and assess their relationship with survival. Methods and results This retrospective cohort study conducted in France from June 2008 to May 2019, at the Henry Mondor Hospital. This cohort included 983 patients with CA. Mean age at inclusion was 73.1 ± 11.4 years, 726 (75.1%) were male and the mean body mass index was 24.5 ± 4.1 kg/m2. Among them, 321 had immunoglobulin light chain (AL) amyloidosis, 434 had wild‐type transthyretin (ATTRwt), and 212 had hereditary transthyretin (ATTRv). The first AECE and/or ACE occurred at a mean age of 63 ± 11 years for AL and ATTRv, and 70 ± 12 years for ATTRwt (P

Systemic light-chain (AL) amyloidosis is a plasma cell disorder characterized by extracellular deposition of monoclonal immunoglobulin light chains leading to organ dysfunction. Cardiac involvement...

Increased cardiac uptake (CU) on early-phase 99mTc-HMDP scintigraphy has demonstrated diagnostic and prognostic values in amyloid transthyretin (ATTR) cardiac amyloidosis (CA). Extracardiac uptake (ECU) has been poorly studied. We assessed the clinical value of ECU, in combination with CU, on 99mTc-HMDP scintigraphy using a novel Methodological Amyloidosis Diagnostic Index (MADI). We reviewed all patients referred for suspicion of CA, who underwent 99mTc-HMDP scintigraphy over an 8-year period. ECU, CU, and MADI were determined: MADI0 = neither ECU or CU, MADI1 = ECU alone, MADI2 = CU alone, and MADI3 = ECU + CU. Of 308 eligible patients, 247 had CA, including 75 ATTRv, 107 ATTRwt, and 65 light-chain (AL), while 61 had another cardiopathy (controls). ECU was observed in 29% of CA and 3% of controls. Most frequent sites of ECU were pleuropulmonary (16% of CA, 3% of controls) followed by the digestive tract and subcutaneous tissues. The liver and spleen ECU was only observed in AL-CA (n = 8). CU was only observed in CA patients (n = 187), of whom 182 had ATTR-CA vs. 5 AL-CA, P 0 vs. MADI0 in AL and MADI3 vs. MADI2 in ATTR were associated with a worse prognosis (P = 0.03 and P = 0.002, respectively). ECU combined with CU demonstrates high diagnostic and prognostic values in CA patients. MADI seems an easy and reliable score in clinical practice.

The three main cardiac amyloidosis (CA) types have different progression and prognosis. Little is known about the mode of death (MOD) which is commonly attributed to cardiovascular causes in CA. Improving MOD’s knowledge could allow to adapt patient care. This retrospective study describes the MOD that occurred during long-term follow-up in CA patients in light-chain (AL), transthyretin hereditary (ATTRv) or wild-type (ATTRwt). Patients referred to and cared for, at the French referral centre for CA, Henri Mondor Hospital, Créteil between 2010 and 2016 were included. Clinical information surrounding patient deaths were investigated and centrally evaluated by two blinded clinical committees which classified MOD as cardiovascular, non-cardiovascular or unknown and sub-classified it depending on its subtype. From the 566 patients included, 187 had AL, 206 ATTRv and 173 ATTRwt. During the 864 patient-year follow-up, 160 (28%) deaths occurred, with median survival time of 17.3 months (interquartile range 5.1–35.4). The most frequent MOD was cardiovascular (64%) of which worsening heart failure occurred most frequently and for which, 69% were of AL subtype, 79% ATTRv and 76% ATTRwt. Sudden death also occurred more frequently in AL subtype accounting for 29% of AL deaths. Non-cardiovascular MOD occurred in 26% of patients overall. Among these, infection was the most common non-cardiovascular MOD in any type of CA (80%). Mortality is high during natural course of CA and differs between subtypes. The main MOD were worsening heart failure, sudden death and infection, opening room to optimise management.

Aims: Multimodal imaging has allowed cardiac amyloidosis (CA) to be increasingly recognised as a treatable cause of heart failure with preserved ejection fraction, but its prognosis remains poor due to late diagnosis. To assess the left ventricular diastolic function (LVDF) patterns in a large contemporary CA cohort according to the current recommendations and to identify their determinants. Methods and Results: We conducted a monocentric, observational study on a cohort of CA patients from a tertiary CA referral centre. Diastolic function was analysed using standard echocardiography and clinical, laboratory and survival parameters were collected. Four hundred and sixty-four patients with one of the three main type of CA were included: 41% had grade III diastolic dysfunction (restrictive mitral pattern), 25% had grade II diastolic dysfunction, and 25% had grade I diastolic dysfunction, 9% were unclassified. No difference was found between the main CA types. After multivariate analyses, grades II and III were independently associated with dyspnoea, elevated NT-proBNP, cardiac infiltration and systolic dysfunction (global longitudinal strain). Grade I patients had a better prognosis. Conclusions: All LVDF patterns can be observed in CA. One quarter of CA patients have grade I LVDF, reflecting the emergence of earlier stage-related phenotypes with a better prognosis.

INTRODUCTION AL amyloidosis is caused by the proliferation of an immunoglobulin-secreting B cell clone. AA amyloidosis is a rare complication of chronic inflammation. However, some patients present with diseases combining monoclonal immunoglobulin production and chronic inflammation. The aim of this work was to describe cases of AA amyloidosis associated with monoclonal gammopathies. PATIENTS AND METHODS We reviewed all patients reported in French national amyloid centres presenting with AA amyloidosis and monoclonal gammopathy and performed a literature review. The quality of AA amyloidosis diagnosis and the causal relationship with monoclonal gammopathy were assessed. RESULTS In total, four patients from our centres and eight from the literature fulfilled the inclusion criteria. The haematological disorders presenting with monoclonal gammopathy were as follows: Waldenstrom macroglobulinaemia (n = 8), Schnitzler syndrome (n = 2), multiple myeloma (n = 1) and monoclonal gammopathy of undetermined significance (n = 1). Treatment strategies varied among the cases, with the treatment of the haematological disorder in 4 and anti-inflammatory treatment in 2. CONCLUSION Monoclonal gammopathies might be a rare and poorly known cause of AA amyloidosis. Such monoclonal gammopathies could be named "monoclonal gammopathies of inflammatory significance."

We evaluated the diagnostic performance of 18F-NaF PET/MRI in patients with suspected cardiac amyloidosis (CA). Twenty-seven consecutive patients underwent myocardial PET 1 hour after injection of 4 MBq/kg 18F-NaF with simultaneous MRI including cine-MRI, T1 and T2 mapping, first-pass and late gadolinium enhancement (LGE). 18F-NaF uptake was measured visually and semi-quantitatively by calculating myocardium-to-blood pool (M/B) ratios. CA was confirmed histologically. Transthyretin (TTR)-CA was diagnosed in 16 patients, light-chain (AL)-CA in 7, and no-CA in 4. Visual interpretation of 18F-NaF images revealed a relative increase in myocardial uptake in only 3 patients, all with TTR CA, and a relative decrease in 13, including 7 AL CA, 3 no-CA, and 3 TTR CA. M/B ratios were significantly higher in TTR CA (1.00 ± 0.12) than in AL CA (0.81 ± 0.06, P = 0.001) or in no-CA (0.73 ± 0.16, P = 0.006). The optimal M/B cut-off to distinguish TTR CA from AL CA was ≥ 0.90 (Fischer, P = 0.0005). By comparison, classification of patients using 99mTc-HMDP heart-to-mediastinum ratios with the previously published cut-off ≥ 1.21 reached higher significance (P < 0.0001). Among MRI parameters, myocardial T1, LGE score, and extracellular volume were higher in CA than in no-CA patients, 1409 ± 76 vs 1278 ± 35 ms (P = 0.004), 10.35 ± 5.30 vs 3.50 ± 3.42 (P = 0.03), and 46 ± 10 vs 33 ± 8 % (P = 0.01), respectively. 18F-NaF PET/MRI shows good diagnostic performance when semi-quantification is used. However, contrast is low and visual interpretation may be challenging in routine. PET/MRI could constitute a one-stop-shop evaluation of amyloid load and cardiac function in patients needing rapid work-up.

Background: Hereditary transthyretin (TTR) related amyloidosis (ATTRv) is a life-threatening condition, which can potentially affect all organs. The objective was to identify the hearing st...

Background: Systemic amyloidosis with cardiac involvement (CA) is a severe disease caused by the aggregation of misfolded proteins infiltrating organs and tissues and leading to their dysfunction. ...

BACKGROUND: Donor-specific antibodies are associated with increased risk of antibody-mediated rejection and decreased allograft survival. Therefore, reducing the risk of these antibodies remains a clinical need in transplantation. Plasma cells are a logical target of therapy given their critical role in antibody production. METHODS: To target plasma cells, we treated sensitized rhesus macaques with daratumumab (anti-CD38 mAb). Before transplant, we sensitized eight macaques with two sequential skin grafts from MHC-mismatched donors; four of them were also desensitized with daratumumab and plerixafor (anti-CXCR4). We also treated two patients with daratumumab in the context of transplant. RESULTS: The animals treated with daratumumab had significantly reduced donor-specific antibody levels compared with untreated controls (57.9% versus 13% reduction; P

Aims Cardiac fibrosis is associated with left ventricular (LV) remodelling and contractile dysfunction in aortic stenosis (AS). The fibrotic process in this condition is still unclear. The aim of this study was to determine the role of both local and systemic inflammation as underlying mechanisms of LV fibrosis and contractile dysfunction. The diagnostic values of 2D‐strain echocardiography and serum biomarkers in the evaluation of cardiac fibrosis in this condition were assessed through correlation analyses. Methods and results Patients with AS referred for surgical valve replacement were prospectively and consecutively included. They all had a comprehensive echocardiography including 2D strain. Blood samples were collected to measure cytokines and inflammatory biomarkers using Luminex bead‐based assays. A per‐surgical myocardial biopsy of the basal antero‐septal segment (S1) was performed. Serial sections of each biopsy were stained with Sirius red. Digital image analysis was used to quantify fibrosis. Immunostainings using specific antibodies against macrophage, glycoprotein (gp) 130, and interleukin 6 (IL‐6) were also performed. Patients were divided into tertiles reflecting the severity of fibrosis: mild, moderate, and severe load (TF1 to TF3). The mean age of the 58 included patients was 73 ± 11 years. Twenty‐four (43%) were in New York Heart Association III–IV. Mean aortic valve area was 0.8 ± 0.2 cm2. Mean aortic stenosis peak velocity and mean gradient were respectively 4.5 ± 0.8 m/s and 54 ± 15 mmHg. The mean LV ejection fraction was 54 ± 12%, and the global LV longitudinal strain was −15 ± 4%. The mean S1 strain, corresponding to the biopsied region, was −10 ± 6% and was strongly correlated to fibrosis load (R = 0.83, P

Heart failure with preserved ejection fraction (HFpEF) is an increasingly diagnosed condition whose failure to respond to new drugs effective in heart failure with reduced ejection fraction is of great concern. HFpEF is an incompletely understood and markedly heterogeneous syndrome, but cardiac amyloidosis is increasingly recognized as one of its various causes. The specific hemodynamic and pathophysiological features of cardiac amyloidosis result in poor tolerance of heart failure medications and in worse outcomes compared with other causes. Until recently, patients considered for HFpEF trials were not routinely screened for cardiac amyloidosis. This review examines how real-world patients with cardiac amyloidosis met inclusion criteria for 8 major HFpEF clinical trials, including the recent PARAGON (Prospective Comparison of ARNI with ARB Global Outcomes in HF With Preserved Ejection Fraction) trial. This review discusses how the presence in the trial populations of a subset of patients with cardiac amyloidosis might contribute to explain the absence of efficacy of medications for HFpEF in trials so far. A multistep screening strategy is suggested in which patients with red flags for cardiac amyloidosis undergo both a light chain assay and technetium-labeled cardiac scintigraphy (technetium-labeled cardiac scintigraphy scan), which, when negative, rule out cardiac amyloidosis. Using this strategy would allow the testing of new medications for HFpEF in populations containing no patients with cardiac amyloidosis, thus potentially increasing the likelihood of showing therapeutic efficacy, and finally making some effective treatment available.

Increased cardiac uptake (CU) on early-phaseWe reviewed all patients referred for suspicion of CA, who underwentOf 308 eligible patients, 247 had CA, including 75 ATTRv, 107 ATTRwt, and 65 light-chain (AL), while 61 had another cardiopathy (controls). ECU was observed in 29% of CA and 3% of controls. Most frequent sites of ECU were pleuropulmonary (16% of CA, 3% of controls) followed by the digestive tract and subcutaneous tissues. The liver and spleen ECU was only observed in AL-CA (n = 8). CU was only observed in CA patients (n = 187), of whom 182 had ATTR-CA vs. 5 AL-CA, P 0.001. MADI0 was only observed in controls (97%) and in AL-CA (60%). MADI1 was mainly observed in AL-CA (positive predictive value, PPV = 91%) while MADI2/3 were more frequent in ATTR-CA (PPV = 97%), P 0.0001. MADI 0 vs. MADI0 in AL and MADI3 vs. MADI2 in ATTR were associated with a worse prognosis (P = 0.03 and P = 0.002, respectively).ECU combined with CU demonstrates high diagnostic and prognostic values in CA patients. MADI seems an easy and reliable score in clinical practice.

A decreased longitudinal strain in basal segments with a base-to-apex gradient has been described in patients with cardiac amyloidosis (CA). Aim was to investigate the left ventricular (LV) regional distribution of early-phase 99mTc-Hydroxymethylene diphosphonate (99mTc-HMDP) uptake in patients with transthyretin-related cardiac amyloidosis (TTR-CA). All patients underwent a whole-body planar 99mTc-HMDP scintigraphy acquired at 10-min post-injection (early-phase) followed by a thorax SPECT/CT. The segmental uptake (expressed as % of maximal myocardial HMDP uptake) was investigated on the AHA 17-segment model and 3-segment model (basal, mid-cavity, apical). Sixty-one TTR-CA patients were included of whom 29 were wild-type (wt-TTR-CA) and 32 had hereditary TTR-CA (m-TTR-CA). Early myocardial 99mTc-HMDP uptake occurred in all TTR-CA. In all patients, segmental analysis of the LV myocardial distribution of 99mTc-HMDP uptake showed an increased median uptake (interquartile range) in basal/mid-cavity segments compared to the lowest median uptake of apical segments (respectively, 79% [72%-86%] vs. 72% [64%-81%]; P

Summary Background The effectiveness of transitional care services for patients discharged from hospital after acute heart failure is challenging, especially in terms of reducing subsequent heart failure hospitalizations. The increased adoption of smartphone applications in society offers a new opportunity to interact with patients to avoid rehospitalization. Thus, electronic health (e-health) can enhance the impact of existing therapeutic education programmes. Aims To determine the prevalence of smartphone use among patients with chronic heart failure, and to assess the epidemiological characteristics and therapeutic management of these patients, with a broader aim of developing smartphone-based therapeutic education programmes for patients. Methods The French Observatoire francais de l’insuffisance cardiaque et du sel (OFICSel) registry was conducted in 2017 by 300 cardiologists, and included both inpatients and outpatients who had been hospitalized for heart failure at least once in the previous 5 years. Data collection included demographic and heart failure-related variables, which were provided by the cardiologist and by the patient via a questionnaire. Results Among the 2822 patients included, 2517 completed the questionnaire. Of this total, 907 patients (36%) were smartphone users. Compared with non-users, smartphone users were younger, were more frequently men, more frequently lived in cities, had a higher educational level and were more frequently professionally active. Smartphone users less frequently had diabetes, hypertension, atrial fibrillation or ischaemic cardiopathy. Only 22% of patients were actively participating in a therapeutic education programme. Conclusion Smartphones were used by more than one-third of patients with heart failure in France in 2017, underscoring the feasibility of developing a smartphone application to deliver therapeutic education to the population with chronic heart failure.

Objective To describe the prevalence of and risk factors for renal infarction (RI) in patients with cardiac amyloidosis. Patients and Methods We evaluated 87 patients with cardiac amyloidosis who underwent renal technetium-99m-labeled dimercaptosuccinic acid scintigraphy in the Amyloidosis Referral Center of Henri-Mondor Hospital from October 1, 2015, through February 28, 2018. Results Three groups of patients were identified according to the underlying amyloidosis disorder: AL amyloidosis in 24 patients, mutated-transthyretin amyloidosis in 24 patients, and wild-type transthyretin amyloidosis in 39 patients. Patients with wild-type transthyretin amyloidosis were older (P Conclusion Our study suggests that prevalence of RI in patients with cardiac amyloidosis is higher than previously thought, regardless of the underlying amyloidosis disorder. Acute kidney injury in a patient with cardiac amyloidosis should alert clinicians to the possibility of RI.

This study sought to compare the intensity of early-phase myocardial uptake of two phosphonate-based radiotracers, 99mTc-hydroxymethylene diphosphonate (HMDP) and 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD), in patients with hereditary transthyretin-related cardiac amyloidosis (TTR-CA). Six patients with biopsy-proven diagnosis of TTR-CA and characteristic amyloid fibril composition underwent early-phase 99mTc-HMDP myocardial scintigraphy as part of their routine workup; they were later assessed by 99mTc-DPD scintigraphy after having signed informed written consent. Heart-to-mediastinum-ratio was measured at both time points as well as regional distribution on 17-segment analysis. All patients had an H/M ratio >1.28 on both imaging. 99mTc-DPD uptake was slightly higher than 99mTc-HMDP uptake in 3 patients, but no statistical difference was found (P = 0.13). Regional distribution of the two radiotracers was well correlated on bull’s eyes analysis, with only slight underestimation of 99mTc-DPD uptake in the anterior/apical segments, compared with 99mTc-HMDP. 99mTc-HMDP and 99mTc-DPD show comparable myocardial uptake intensity on early-phase scintigraphy and can be used alternatively for the diagnosis of TTR-CA.

Cardiac amyloidosis must be suspected in all cases of hypertrophic cardiomyopathy with preserved left ventricular ejection fraction to allow specific management. Final diagnosis needs pathological evidence, but bone scintigraphy may be an alternative for TTR amyloidosis. Invasive samplings are limited by new tools. Amyloidosis typing is required to start specific therapies if possible. Main specific treatments that are available are chemotherapy for AL; transthyretin stabilizer or gene therapy, studied for TTR-related cardiac amyloidosis.

Obstructive sleep apnoea syndrome (OSAS) is a frequent sleep disorder that is known to be an independent risk factor for arterial hypertension (AHT). Potential confounding factors associated with both OSAS and AHT, such as age, diabetes mellitus and obesity, have been explored extensively, and are considered as independent but additive factors. However, these factors are also contributors to left ventricular (LV) hypertrophy (LVH) and LV diastolic dysfunction, both of which are important causes of cardiovascular morbidity, and have been reported to be associated with OSAS for decades. In this review, we present an overview of how OSAS may promote changes in LV geometry and diastolic dysfunction through its best-known cardiovascular complication, arterial hypertension. We also summarize the epidemiological links between OSAS and LVH, outline diastolic dysfunction in OSAS patients, and try to highlight the mechanisms responsible, focusing on the effect of confounding factors.

Background: The prognosis of amyloidosis is known to depend heavily on cardiac function and may be improved by identifying patients at highest risk for adverse cardiac events.Aims: Identify predictors of mortality in patients with cardiac light-chain amyloidosis (AL), hereditary transthyretin amyloidosis (m-TTR), or wild-type transthyretin amyloidosis (WT-TTR) to prompt physician to refer these patients to dedicated centers.Methods and results: Observational study. About 266 patients referred for suspected cardiac amyloidosis (CA) in two French university centers were included. About 198 patients had CA (AL = 118, m-TTR = 57, and WT-TTR = 23). Their median (25th–75th percentile) age, NT-proBNP left ventricular ejection fraction were, respectively, 68 years (59–76), 2339 pg mL−1 (424–5974), and 60% (48–66). About 31% were in NYHA class III–IV. Interventricular septal thickness was greater in the m-TTR and WT-TTR groups than in the AL group (p

To assess prevalence, severity, and prognostic value of sleep-disordered breathing (SDB), in the three main cardiac amyloidosis (CA) types, i.e., light-chain (AL), transthyretin-related familial (m-TTR), or senile (WT-TTR).Patients consecutively referred for CA diagnosis work-up underwent cardiac assessment and nocturnal polygraphy. SDB was defined as apnea-hypopnea index (AHI) ≥ 5/h. Multivariate analysis was used to identify predictors of a major adverse cardiac event (MACE) defined as death, heart transplantation and acute heart failure.Seventy CA patients were included (31 AL, 22 m-TTR, 17 WT-TTR). The mean ± standard deviation age and left ventricular ejection fraction were 71 ± 12 years and 49% ± 13% and median (interquartile range) N terminal pro brain natriuretic peptide (NT-proBNP) was 3,932 (1,607; 7,028) pg/mL. The prevalence of SDB was 90% without difference between amyloidosis types. SDB was central in 27% and obstructive in 73%. AL had less frequent severe SDB compared to m-TTR and WT-TTR (P = 0.015) but longer time with peripheral capillary oxygen saturation (SpO2)90% (P = 0.037). After a median follow-up of 7.5 (2.8; 14.9) months, 49% patients experienced MACE. Time with nocturnal SpO290% was the only independent predictor of MACE. The best-identified threshold was 30 min. Values30 min were associated with bad prognosis (Log-rank χ(2): 8.01, P value = 0.005). Using binomial logistic regression, determinants of time with nocturnal SpO290% were New York Heart Association class (P = 0.011), and log-NT-proBNP (P = 0.04) but not AHI.In CA population, prevalence of SDB is high (90%) and dominated by the obstructive pattern. Bad prognosis in this population was driven by nocturnal desaturation, reflecting heart failure severity and respiratory involvement.

International audience; Background Aortic stenosis (AS) and transthyretin cardiac amyloidosis (TTR-CA) are both frequent in elderly. The combination of these two diseases has never been investigated. Aims To describe patients with concomitant AS and TTR-CA. Methods Six cardiologic French centres identified retrospectively cases of patients with severe or moderate AS associated with TTR-CA hospitalized during the last 6 years. Results Sixteen patients were included. Mean +/- SD age was 79 +/- 6 years, 81% were men. Sixty per cent were NYHA III-IV, 31% had carpal tunnel syndrome, and 56% had atrial fibrillation. Median (Q1; Q4) NT-proBNP was 4382 ( 2425; 4730) pg/mL and 91% had elevated cardiac troponin level. Eighty-eight per cent had severe AS (n = 14/16), of whom 86% (n = 12) had low-gradient AS. Mean +/- SD interventricular septum thickness was 18 +/- 4 mm. Mean left ventricular ejection fraction and global LS were 50 +/- 13% and -7 +/- 4%, respectively. Diagnosis of TTR-CAwas histologically proven in 38%, and was based on strong cardiac uptake of the tracer at biphosphonate scintigraphy in the rest. Eighty-one per cent had wild-type TTR-CA (n = 13), one had mutated Val122l and 19% did not had genetic test (n = 3). Valve replacement was surgical in 63% and via transcatheter in 13%. Median follow-up in survivors was 33 (16; 65) months. Mortality was of 44% (n = 7) during the whole follow-up period. Conclusions Combination of AS and TTR-CA may occur in elderly patients particularly those with a low-flow low-gradient AS pattern and carries bad prognosis. Diagnosis of TTR-CA in AS is relevant to discuss specific treatment and management.

Objectives The aim of this study was to compare left ventricular longitudinal strain (LS) evaluated by 2-dimensional echocardiography with cardiac magnetic resonance (CMR) in cardiac amyloidosis (CA), establish correlations between histological and imaging findings, and assess the prognostic usefulness of LS measurement and CMR. Background CA is a condition with a poor prognosis due chiefly to 3 forms of amyloidosis: light-chain amyloidosis (AL), hereditary transthyretin (M-TTR), and wild-type transthyretin (WT-TTR). Two-dimensional echocardiography measurement of LS has been reported to detect early left ventricular systolic dysfunction. The pathophysiological underpinnings, regional distribution, and prognostic significance of LS in CA are unclear. Methods All patients underwent echocardiography, and 53 underwent CMR. The native hearts of the 3 patients who received heart transplants were subjected to histological examination. For each of the 17 left ventricular segments in the American Heart Association model, we evaluated LS, late gadolinium enhancement (LGE) by CMR, and cardiac amyloid deposition. Univariate and multivariate analyses were performed at 6 months to identify variables associated with major adverse cardiac events (MACE). Results We studied 79 patients with CA; 26 had AL, 36 M-TTR, and 17 WT-TTR. Mean LS was −10 ± 4%. Both LS and amyloid deposits showed a basal-to-apical gradient. The mean LS and number of segments with LGE were similar across the 3 CA types. LS correlated with LGE and amyloid burden (r = 0.72). LGE was seen in the 6 basal segments in all WT-TTR patients. During the median follow-up of 11 months (range 4 to 17 months), 36 (46%) patients experienced MACE. Independent predictors of MACE were apical LS (cutoff, −14.5%), N-terminal pro–B-type natriuretic peptide (cutoff, 4,000 ng/l), and New York Heart Association functional class III to IV heart failure. Conclusions Basal-to-apical LS abnormalities are similar across CA types and reflect the amyloid burden. Apical LS independently predicts MACE.

Although bisphosphonate scintigraphy has emerged as a valuable modality for cardiac amyloidosis (CA) diagnosis and typing with transthyretin CA showing strong cardiac uptake [(1)][1], the procedure in its current form is time consuming and may be regarded as inadequate especially in frail patients.

Background To assess the diagnostic and prognosis value of myocardial native T2 measurement in the distinction between Light-chain (AL) and Transthyretin (ATTR) cardiac amyloidosis (CA). Methods Forty-four patients with CA (24 AL; 20 ATTR) and 40 healthy subjects underwent 1.5 T cardiovascular magnetic resonance (CMR). They all underwent T1 and T2 mapping (modified Look-Locker inversion recovery), cine and late gadolinium enhancement (LGE) imaging. The Query Amyloid Late Enhancement (QALE) score, myocardial native T2, T1 and extra cellular volume fraction (ECV) were calculated for all patients. Results Of the 44 patients, 36 (82%) exhibited enhancement on LGE images. Mean QALE score of AL (7.9 ± 6) and ATTR (10.5 ± 5) patients were similar (p = 0.6). Myocardial native T2 was significantly (p

Background Light-chain amyloidosis (AL) with cardiac involvement carries a poor prognosis; median untreated survival is Purpose Our study evaluates the effect on mortality of first-line chemotherapy administered in combined or in sequential in patients with cardiac AL. Methods Two hundred and sixty-two patients diagnosed with AL amyloidosis were retrospectively studied, since 2008. Among these patients, 34% already received chemotherapy and 15% were not treated or treated in another hospital. 51% patients newly diagnosed had a medical follow-up in our center, of whom 3% died before receiving chemotherapy. A total of 131 patients were analyzed. Initial chemotherapies administered were classified into 4 groups according to the sequence of administration: combination of Velcade (Bortzezomib)/Cyclophosphamide/Dexamethasone (VADcomb), sequential administration of Dexamethasone/Velcade/Cyclophosphamide (DCVseq) or Cyclophosphamide/Velcade/Dexamethasone (CVDseq) and other chemotherapy. Survival was assessed using a log-rank test ( Fig. 1 , Table 1 ). Results Among 131 treated patients (65,5years ± 11.6, 63% male, 73% lambda subtype), 57 received CVDseq, 18 DCVseq, 38 VADcomb and 18 other chemotherapy. At 1 month, mortality was 16.5%, and mortality per group was 17% in CVDseq group, 16.7% in DCVseq group, 16.7% in other chemotherapy group and 15.8% in VADcomb group. Overall mortality is 45% and mortality per group is 40% with CVDseq, 44% with DCV seq, 50% with VADcomb and 50% with other chemotherapy. Conclusion Overall mortality and mortality at 1 month were not significantly different between the 4 groups (respectively P = 0.785 and P = 0.99). There is no difference of mortality in the cohort whether the chemotherapy is administered sequentially or in combination.

Background Therapeutic education (TE) and follow-up in heart failure (HF) patients are mandatory. This could be eased by new technologies, particularly with smartphone use. There is no data about the characteristics of the patients using a smartphone in this population. Purpose Evaluate the prevalence and the epidemiological characteristics of HF patients with smartphone in a large sample of HF patients. Methods The OFICsel observatory include 180 French HF centers. Out and in-patients hospitalized for acute HF during the last five years were included in the study. Data collection included a Physician and Patient questionnaires including clinical, echocardiographical, biological and treatment characteristics. Patients recorded their own sociodemographic data. Results From March to June 2017, a total of 2517 patients completed the questionnaire. Of these patients, 907 (36%) patients had a smartphone, 1553 (59%) had an Internet connection and 1454 (58%) had an e-mail address. When comparing with patients who didn’t have a smartphone, patients who had a smartphone were younger (59.5 vs. 71.6 years old P Conclusion HF Patients using a smartphone represented 1/3 of our population, were younger, more likely to have a urban way of life, and with a higher level of education. This highlights the type of patients who would benefit from an educational program supported by a HF smartphone's application.

Background Heart Failure (HF) is a major public health problem resulting in high rates of hospitalization and mortality. Most HF Surveys have included selected HF patients and did not focus on HF life burden. Purpose To describe a large French HF population (de novo/chronic/acute; out and in-patients; consultation/hospitalization/rehabilitation; LVEF preserved/reduced, any type of cardiologist’ practice). Methods Prospective enrolment during 6 months in 2017. Data collection included demographic, burden, clinical, biological, echocardiography, treatment and diet characteristics. Results A total 2822 HF patients (70% men, mean age 67 ± 14 years) from 79 French departments of cardiology were included ( Table 1 ). Thirty-six percent were outpatients, 53% were hospitalized and 11% were in rehabilitation center. Sixteen percent were de novo and 31% were in Acute HF. Fifty percent have been hospitalized during the previous year for Acute HF. Seventy-nine were in NYHA II or III and the mean LVEF was 38.8 ± 13.7%. 32% lived in the Countryside vs. 68% in Town. Thirty percent lived alone, 50% with a partner and 18% with their family and 1.5% in a Care home. Sixty-eight percent have level of education below Baccalaureat. Eighty-eight percent were non-working patients: 70% were retired; 9% were in sick Leave and 9% were unemployed. Regarding their self-sufficiency, 84% reported limitation of their life activities because of HF symptoms: 45% did not do their own cooking, 51% can not do their shopping, which is done by their partner (33%), by other members of the family (13%), by care givers (2%), by home delivery (2%), or by neighbours (1%). Seventy-four percent had Long Term Public Health Insurance (HI) (ALD), 40% had a Private HI, 4% had a Universal HI (CMU) and 0.5% reported none. Only 33% were asked to enter in an Education Program and of whom 65% did. Conclusion Heart failure is more prevalent in men with low level of education and leads to heavy life burden because of vital exhaustion and life dependency that are reinforced by social isolation.

Background Face-to-face Patient's Education Programs (PEP) have been widely developed in France to improve treatment and diet restriction regimens (DRR) observance in Heart Failure (HF). Internet or Smartphone's Application Used (ISAU) may improve communication and education therefore data are lacking concerning the use of these technics in this Elderly population. Purpose Determine prevalence of ISAU, DRR and PEP prescription and their observance in HF. Methods OFICSel observatory included out and in HF patients hospitalized for HF at least one time for the last five years (whatever their LVEF). Data were obtained from a physician and patient questionnaires. Results Of the 2822 patients included in 2017, 2517 completed the questions regarding the use of new technologies of whom 1553(59%) had an Internet Connection (IC), 1454(58%) an e-mail address and 907(36%) were Smartphone's Application Used (SAU). Prescription of salt, sugar, lipid and fluid DRR in the overall cohort were respectively of 79.3%, 40.0%, 49,6% and 26.2%. Only 33.5% reported having being invited to PEP of whom only 66.2% did. The every day life compliances of these DRR were respectively for salt, sugar, lipid and fluid of: 44.2%, 45.4%, 33.1% and 41.8%. 20.4% of the overall population weighed every day. When comparing with patients who didn’t have ISAU, patients who had ISAU were younger (63 vs. 73 years old for IC and 60 vs. 72 years old for SAU, P Conclusion Restriction diet regimens are frequently prescribed in HF therefore their observance is low. Usage of internet is large in HF patients suggesting that developing new HF education tools through dedicated website or smartphone application might be useful in HF population.

Cardiac involvement is common in sickle cell disease (SCD). Studies are needed to establish haematological determinants of this involvement and prognostic markers. The aim of the study was to identify haematological factors associated with cardiac involvement in SCD and their impact on prognosis.This longitudinal observational study was performed on 1780 SCD patients with SS or S-β(0)-thalassemia referred to our centre. Six hundred fifty-six met our inclusion criteria (availability of a blood-workup and echocardiogram obtained1 year apart, no heart valve surgery and no current pregnancy). Median age was 31 (interquartile range, 25-40) years, and median haemoglobin (Hb) was 87 (80-95)g/L. Left ventricular (LV) dilation, left atrial dilation, cardiac index (CI)4 L/min/m(2), LV ejection fraction55%, and tricuspid regurgitant velocity (TRV) ≥2.5 m/s were found in 35, 78, 23, 8.5, and 17% of patients, respectively. Compared with other patients, those in the fourth quartiles (Q4) of LV end-diastolic dimension index (LVEDDind) and left atrial dimension index (LADind) and those with high CI had significantly lower Hb, % foetal Hb (HbF), and red blood cell (RBC) counts; and significantly higher lactate dehydrogenase, bilirubin, and %dense RBCs. Independent haematologic determinants of Q4 LVEDDind and LADind were low RBC count and %HbF; high %dense RBCs were associated with LADind. Low %HbF and RBC count were associated with high CI. High %dense RBCs or no α-thalassemia gene deletion was associated with greater severity of anaemia and cardiac dilation and with higher CI. During the median follow-up of 48 (32-59) months, 50 (7.6%) patients died. Tricuspid regurgitant velocity ≥ 2.5 m/s was a predictor of mortality. The risk of death increased four-fold when left ventricular ejection fraction55% was present also (P = 0.0001).Cardiac dilation and CI elevation in patients with SCD are associated with haematologic variables reflecting haemolysis, RBC rigidity, and blood viscosity. Tricuspid regurgitant velocity ≥ 2.5 and LV dysfunction (even mild) predict mortality.

Background The association between obstructive sleep apnoea syndrome (OSAS), left ventricular (LV) diastolic dysfunction and LV geometry remains controversial because of coexisting disorders. Aims To evaluate LV diastolic dysfunction and its independent predictors in a real-life cohort of OSAS patients, by a standardized approach. Methods We consecutively included 188 OSAS patients after an overnight polysomnography to undergo clinical evaluation, ambulatory blood pressure measurement and complete echocardiography, combining M-mode, two-dimensional Doppler and tissue Doppler imaging modes. Correlations between OSAS severity and clinical and echocardiographical variables were assessed, and logistic regression models were used to identify possible determining factors of LV diastolic dysfunction. Results Most patients were hypertensive (n = 148, 78.7%) and already receiving treatment by continuous positive airway pressure (n = 158, 84.5%). The prevalence of LV hypertrophy, defined by LV mass index (LVMi) normalized by height2.7, was 12.4%, with a significant correlation with hypertension (P = 0.004). The apnoea-hypopnoea index was correlated with body mass index (P

Cardiac amyloidosis (CA) is recognized as a common cause of restrictive cardiomyopathy and heart failure due to the deposition of insoluble proteins in the myocardial interstitium. We emphasize the role of [18F]-sodium fluoride (NaF) PET/CT as a potential noninvasive tool to identify and differentiate the transthyretin-related cardiac amyloidosis from the light-chain cardiac amyloidosis. We report cases of a 73-year-old man and a 75-year-old woman followed in our center for congestive heart failure with marked alteration of the left ventricular ejection fraction due to familial transthyretin Val122Ile cardiac amyloidosis and light-chain cardiac amyloidosis, respectively, confirmed on endomyocardial biopsy.

Aims Sleep-disordered breathing (SDB) is highly prevalent and of adverse prognostic significance in patients with chronic heart failure (CHF). Polygraphy is used for diagnosing SDB but polygraphy resources fall short of needs. Here, our aim was to develop a score for SDB screening in patients with CHF. Methods and results Consecutive patients with stable chronic CHF referred to our CHF clinic for a scheduled follow-up evaluation were included prospectively between 2000 and 2012. SDB was defined as an apnoea–hypopnoea index ≥ 5/h as assessed by routine polygraphy. A screening score was developed as a linear combination of factors independently associated with SDB by multivariate logistic regression. Calibration and discrimination were evaluated using the Hosmer–Lemeshow (HL) test and area under the receiver-operating characteristics curve (AUC), respectively. Bootstrapping was performed to assess internal validity. Of 450 included patients (mean age, 59.5 ± 13.7 years), 397 (88%) had SDB. An easy-to-use score was based on age (2 points if ≥65 years), body mass index (2 points if ≥25 kg/m 2 ), New York Heart Association (NYHA) class (2 points if ≥3 or 4) and male gender (3 points). A score cut-off of 5 was 78.9% sensitive and 61.5% specific for SDB . The final model exhibited adequate calibration ( p HL ≥ 0.3) and discrimination (AUC, 0.737; 95% confidence interval, 0.663; 0.810). Conclusion An easy-to-use clinical score combining age, body mass index, NYHA class, and gender may help to identify those CHF patients most likely to have SDB, thereby improving the allocation of scarce polygraphy resources and early diagnosis of SDB.

Background Left atrial (LA) dysfunction (LAD) and thrombi have been described in systemic light chain (AL) cardiac amyloidosis (CA). The causes and consequences of these alterations are unclear. Purpose To (1) demonstrate that LA 2D-strain echocardiography (2D-SE) is useful to analyze LAD; (2) explore causes, consequences and association of this dysfunction with thromboembolic events (TE) in the three major types of CA. Methods and results Seventy-six patients with CA and in sinus-rhythm were included. 21 had AL, 42 hereditary transthyretin (m-TTR) and 13 wild-type (wt-TTR) CA. History of TE was recorded at baseline. Global and regional LA longitudinal strain (LS) were measured using 2D-SE. Peak atrial LS (PALS-4C) was negatively correlated to NT-proBNP (r = −0.6, P Conclusions Atrial function estimated by 2D-SE is useful to identify patients at risk of death and might be helpful to select those that may benefit from preventive anticoagulant treatment.

e19538 Background: Venetoclax (VEN) is an orally bioavailable small molecule inhibitor of the anti-apoptotic protein BCL-2 and has been shown to have efficacy against myeloma (MM), particularly in patients that harbor t(11;14). Approximately, 50% of AL amyloidosis patients will exhibit t(11;14) making VEN an attractive therapeutic option. Methods: We here report the results of a retrospective analysis of a monocentric series of refractory/relapsed (R/R) patients (pts) heavily pretreated with cardiac AL amyloidosis treated in a french academic center. VEN was given daily alone or in association with dexamethasone (DEX), with or without bortezomib (BTZ). Treatment was planned to be administered until progression. Results: Between February 2017 and January 2019, 7 consecutive R/R pts have been treated. All had received previous BTZ and daratumumab (DARA) containing regimen. Baseline characteristics were: median age: 72.7 years (range 40-84), Mayo Clinic stage: stage I in 2 pts, stage II in 3 and stage IIIA in 2. All patients but one had in addition to cardiac deposit, systemic involvement including kidney, joint, neurologic, gastro-intestinal tract, lymph node and muscle. All but one pts were refractory to their last treatment consisting of DARA-DEX with or without IMID. The t(11;14) translocation was present in 5 pts, absent in 1 and undetermined in 1 pts. Two pts had concomitant MM at diagnosis. Median number of previous line treatments was 4 (3-5). Five patients received VEN- BTZ- DEX as described in MM (PMID: 28847998), 1 with DEX and 1 as monotherapy. Five pts received 400 mg/d, one 200 mg/d and one 100 mg/d. Median duration of treatment was 76 days (30-713). All patients but one are still on treatment. One patient treated with 400 mg/d had a dose reduction to 100 mg/d due to grade 2 diarrhea. Four patients received at least 2 cycles and were evaluable for response. One 84 y old patient in stable disease after 1 cycle died due to influenza infection. 2 patients received only one cycle of treatment. Hematological complete response occurred in 2/4 (50%) patients, after 63 and 27 days. Interestingly, responses were sustained as the 2 responders were still on therapy after 76 and 713 days. This later patient, refractory to 2 previous lines had a cardiac and neurologic response. The 2 responding patients had proven t(11:14). Conclusions: On this limited series of heavily pretreated patients with R/R AL cardiac amyloidosis VEN used as a single agent or in combination can induce prolonged response and seems a promising drug with an acceptable safety profile in patients with t(11;14).

Introduction Cardiac amyloidosis (CA) is a severe disease, often lethal. Little is known about cause of death during the natural course of CA. Identification of cause of death during CA is of particular interest to design clinical trials and identify therapeutic targets in this pathology. We aimed to describe mode of death in CA patients during long-term follow-up, according to the type of amyloidosis. Material and methods All patients consecutively referred to the French referral center for light-chain (AL), transthyretin hereditary (hTTR) or wild-type (WT-TTR) CA were consecutively included between 2010 and 2016 were included. Mode of death was centrally adjudicated by two blinded clinical committees, using multiple sources, and classified as cardiovascular (including worsening heart failure, sudden death, stroke) or non-cardiovascular (1). Results From the 565 patients included, 187 patients had AL amyloidosis, 220 had hTTR and 158 had WT-TTR amyloidosis. One hundred thirty-nine patients (25%) died during a follow-up of 864 patients-years, with median follow-up in survivors 14.6 months (IQR 3.7–33.9). One-year survival was 67% in AL patients, 92% in hTTR patients and 89% in WT-TTR patients (logrank Discussion and Conclusions Mortality is high during natural course of cardiac amyloidosis, significantly different according to CA type. Main causes of death were cardiovascular (mostly worsening heart failure and sudden death), opening room for optimal prevention and management.

Background Heart Failure (HF) is a major public health problem resulting in high rates of hospitalization and mortality. So far, most HF Surveys have included a selected population of patients with HF and involved mainly one type of cardiologic practice. There is a need for more information on the whole HF population. Purpose To collect data on a large French HF population (de novo/chronic/acute; out and in-patients; consultation/hospitalization/rehabilitation; all LVEF classes and any type of cardiologic practice) and to assess low sodium diet prescription and adherence. Methods Prospective enrolment during 6 months in 2017. Data collection included biological, clinical, demographic, dietetary, echocardiographic and treatment characteristics. Results Supervised and unsupervised analysis methods from the data mining and machine learning fields can be performed to exploit data. Baseline variables involved for the analysis (NYHA classes, NTproBNP, Creatinin, BMI, …) are studied among descriptive variables (Age, Sex, Weight, …). Cluster analysis performed are based on Hierarchical Ascending Approaches in Euclidean distance and on the production of Self-Organizing Maps (SOMs) with the statistical software R. Complete data analysis with identification of new patient profiles will be shown at the congress. Conclusion Combining a large representative and non selective French HF population, cluster analysis will allow to identify specific patient profiles constituting homogeneous groups within the sampled population reflecting the severity of their heart condition. New data will be shown during the congress.

Background Care pathways are developed to improve the treatment of heart failure (HF), with uncomplete successful because of lack of time and human medical resources. New technology, numerical tools, and cooperation between doctors and nurses could be answers. Objectives (1) get going medication titration, (2) provide a quick answer to early cardiac decompensation, (3) improve in-hospital pathway and discharge coordination, (4) promote home care, and (5) reduce readmission rate. Methods We transfer knowledge and skills from cardiologists to specialized nurses (cooperation work) in the field of chronic HF: medication titration protocol, telemonitoring, and acute HF management. Medical treatment for HF will be optimized at regular intervals, fitting with European guidelines, by HF nurse under the responsibility of a cardiologist as part of a cooperation protocol. At home, symptoms will be monitored by connected scale and tablet transmitting daily weight and answers to targeted questions. Presence of signs of acute HF sets off an immediate evaluation firstly by phone, then by a face-to-face consultation if needed. HF nurse will be in the front line for this early evaluation in order to reduce the delay between symptoms and therapeutic adaptations, and to refer the patient to the most appropriate structure (GP, cardiologist, hospitalisation or home care), without passing through emergency units, while promoting ambulatory care and improving in-hospital pathway. This cooperation protocol aims to be nationally transposed, to all interested heart failure team, in the hospital or in the office. Perspectives With this new model of cooperation, transfer of skills to HF nurses will enhance the quality of care for HF patients, while medical time will be redistributed to complex cases. Inscription to a specific formation for HF nurses will be possible for academic year 2018-2019, and accession to the cooperation protocol is expected for 2019.

Introduction Cardiac Amyloidosis (CA) is caused by the extracellular accumulation of insoluble fibrillar proteins. The most common types of CA are AL amyloidosis (light-chain), transthyretin amyloidosis: Hereditary (hTTR) or wild-type (wTTR). Without treatment and adequate care management, the prognosis for CA is poor. Heart transplantation is remains the final cardiac therapeutic option. Methods This is a retrospective study that included all patients who had a heart transplant for CA from 2005 to 2018 (n = 18). We report the baseline and post-transplant data follow-up. Results Eighteen patients had a heart transplant: 13 (72%) had AL amyloidosis and 5 had hTTR (28%). The average age was 56 years (43 to 66 years), there were 8 women (44%). Four patients had combined heart and liver transplant (all of them were hTTR). Four patients had combined heart and kidney transplant (all of them were AL). All AL patients received at least one cycle of chemotherapy before the surgery and 8 (62%) were in partial remission. Six patients (33%) were urgently transplanted. The 30-day survival is 100%, the one-year survival was 75%. The deaths occurred only in AL: 3 died from infection and 1 from severe hemorrhage (scarpa rupture), of which one with heart and kidney. No deaths at 1 year were associated with a recurrence of amyloidosis. In most AL with partial remission before the surgery, a slight decrease of light-chains under immunosuppressive treatments was observed. Conclusions Heart transplant is a therapeutic option for selected CA in AL and hTTR and can be combined with kidney or liver transplant. In severe AL CA cardiac transplant need to perform before expecting the complete remission as immunosuppressive therapy may stabilize or decrease the light-chain after the transplant. The survival of transplant CA patients is comparable to that of non-AC patients, and may have better survival than those with a single heart transplant.