Prognostic value of soluble ST2 in AL and TTR cardiac amyloidosis: a multicenter study.

Background: Both light-chain (AL) amyloidosis and transthyretin (ATTR) amyloidosis are types of cardiac amyloidosis (CA) that require accurate prognostic stratification to plan therapeutic strategies and follow-ups. Cardiac biomarkers, e.g., N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (Hs-cTnT), remain the cornerstone of the prognostic assessment. An increased level of soluble suppression of tumorigenesis-2 (sST2) is predictive of adverse events [all-cause death and heart failure (HF) hospitalizations] in patients with HF. This study aimed to evaluate the prognostic value of circulating sST2 levels in AL-CA and ATTR-CA. Methods: We carried out a multicenter study including 133 patients with AL-CA and 152 patients with ATTR-CA. During an elective outpatient visit for the diagnosis of CA, Mayo Clinic staging [NT-proBNP, Hs-cTnT, differential of free light chains (DFLCs)] and sST2 were assessed for all AL patients. Gillmore staging [including estimated glomerular filtration rate (eGFR), NT-proBNP] and Grogan staging (including NT-proBNP and Hs-cTnT) were assessed for TTR-CA patients. Results: The median age was 73 years [interquartile range (IQR) 61-81], and 53% were men. The endpoint was the composite of all-cause death or first HF-related hospitalization. The median follow-up was 20 months (IQR 3-34) in AL amyloidosis and 33 months (6-45) in TTR amyloidosis. The primary outcome occurred in 70 (53%) and 99 (65%) of AL and TTR patients, respectively. sST2 levels were higher in patients with AL-CA than in patients with ATTR-CA: 39 ng/L (26-80) vs. 32 ng/L (21-46), p < 0.001. In AL-CA, sST2 levels predicted the outcome regardless of the Mayo Clinic score (HR: 2.16, 95% CI: 1.17-3.99, p < 0.001). In TTR-CA, sST2 was not predictive of the outcome in multivariate models, including Gillmore staging and Grogan staging (HR: 1.17, CI: 95% 0.77-1.89, p = 0.55). Conclusion: sST2 level is a relevant predictor of death and HF hospitalization in AL cardiac amyloidosis and adds prognostic stratification on top of NT-proBNP, Hs cTnT, and DFLC.

Safety and incremental prognostic value of stress cardiovascular magnetic resonance in patients with known chronic kidney disease.

BACKGROUND: Cardiovascular disease (CVD) is the main cause of mortality in patients with chronic kidney disease (CKD). Although several studies have demonstrated the consistently high prognostic value of stress cardiovascular magnetic resonance (CMR), its prognostic value in patients with CKD is not well established. We aimed to assess the safety and the incremental prognostic value of vasodilator stress perfusion CMR in consecutive symptomatic patients with known CKD. METHODS: Between 2008 and 2021, we conducted a retrospective dual center study with all consecutive symptomatic patients with known stage 3 CKD, defined by estimated glomerular filtration rate (eGFR) between 30 and 60 ml/min/1.73 m2, referred for vasodilator stress CMR. All patients with eGFR < 30 ml/min/1.73 m2 (n = 62) were excluded due the risk of nephrogenic systemic fibrosis. All patients were followed for the occurrence of major adverse cardiovascular events (MACE) defined as cardiac death or recurrent nonfatal myocardial infarction (MI). Cox regression analysis was used to determine the prognostic value of stress CMR parameters. RESULTS: Of 825 patients with known CKD (71.4 ± 8.8 years, 70% men), 769 (93%) completed the CMR protocol. Follow-up was available in 702 (91%) (median follow-up 6.4 (4.0-8.2) years). Stress CMR was well tolerated without occurrence of death or severe adverse event related to the injection of gadolinium or cases of nephrogenic systemic fibrosis. The presence of inducible ischemia was associated with the occurrence of MACE (hazard ratio [HR] 12.50; 95% confidence interval [CI] 7.50-20.8; p < 0.001). In multivariable analysis, ischemia and late gadolinium enhancement were independent predictors of MACE (HR 15.5; 95% CI 7.72 to 30.9; and HR 4.67 [95% CI 2.83-7.68]; respectively, both p < 0.001). After adjustment, stress CMR findings showed the best improvement in model discrimination and reclassification above traditional risk factors (C-statistic improvement: 0.13; NRI = 0.477; IDI = 0.049). CONCLUSIONS: In patients with known stage 3 CKD, stress CMR is safe and its findings have an incremental prognostic value to predict MACE over traditional risk factors.

Predictive value of the TRI-SCORE for in-hospital mortality after redo isolated tricuspid valve surgery.

OBJECTIVES: The TRI-SCORE reliably predicts in-hospital mortality after isolated tricuspid valve surgery (ITVS) on native valve but has not been tested in the setting of redo interventions. We aimed to evaluate the predictive value of the TRI-SCORE for in-hospital mortality in patients with redo ITVS and to compare its accuracy with conventional surgical risk scores. METHODS: Using a mandatory administrative database, we identified all consecutive adult patients who underwent a redo ITVS at 12 French tertiary centres between 2007 and 2017. Baseline characteristics and outcomes were collected from chart review and surgical scores were calculated. RESULTS: We identified 70 patients who underwent a redo ITVS (54±15 years, 63% female). Prior intervention was a tricuspid valve repair in 51% and a replacement in 49%, and was combined with another surgery in 41%. A tricuspid valve replacement was performed in all patients for the redo surgery. Overall, in-hospital mortality and major postoperative complication rates were 10% and 34%, respectively. The TRI-SCORE was the only surgical risk score associated with in-hospital mortality (p=0.005). The area under the receiver operating characteristic curve for the TRI-SCORE was 0.83, much higher than for the logistic EuroSCORE (0.58) or EuroSCORE II (0.61). The TRI-SCORE was also associated with major postoperative complication rates and survival free of readmissions for heart failure. CONCLUSION: Redo ITVS was rarely performed and was associated with an overall high in-hospital mortality and morbidity, but hiding important individual disparities. The TRI-SCORE accurately predicted in-hospital mortality after redo ITVS and may guide clinical decision-making process (www.tri-score.com).

N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T hold diagnostic value in cardiac amyloidosis.

AIMS: Cardiac amyloidosis (CA) is associated with an elevation of natriuretic peptides and troponins, predicting outcome. Nevertheless, the diagnostic yield of these biomarkers has not been extensively investigated. This study aimed to evaluate the diagnostic performance for CA of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT). METHODS AND RESULTS: Patients with suspected CA (n = 1149) underwent a diagnostic work-up in three centres in Italy, France (n = 343, derivation cohort), and United Kingdom (n = 806, validation cohort). Biomarker values with either 100% sensitivity or ≥95% specificity were selected as rule-out/rule-in cut-offs, respectively. In the derivation cohort, 227 patients (66%) had CA, and presented with higher NT-proBNP and hs-TnT. NT-proBNP 180 ng/L and hs-TnT 14 ng/L were selected as rule-out cut-offs, and hs-TnT 86 ng/L as rule-in cut-off. NT-proBNP <180 ng/L or hs-TnT <14 ng/L were found in 7% of patients, and ruled out CA without false negatives. In the validation cohort, 20% of patients (2% false negatives) had NT-proBNP <180 ng/L or hs-TnT <14 ng/L, and 10% showed both biomarkers below cut-offs (0.5% false negatives). These cut-offs refined CA prediction when added to echocardiographic scores in patients with a haematologic disease or an increased wall thickness. In the validation cohort, the 86 ng/L hs-TnT cut-off ruled in 20% of patients (2% false positives). NT-proBNP and hs-TnT cut-offs retained their rule-out and rule-in performance also in cohorts with CA prevalence of 20%, 10%, 5% and 1% derived from the original cohort through bootstrap analysis. CONCLUSIONS: Cardiac biomarkers can refine the diagnostic algorithm in patients with suspected CA. NT-proBNP <180 ng/L and hs-TnT <14 ng/L reliably exclude the diagnosis, both in the overall population and subgroups referred for either AL-CA or cardiac (pseudo)hypertrophy.

Safety, feasibility, and prognostic value of stress perfusion CMR in patients with MR-conditional pacemaker.

AIMS: To assess the safety, feasibility, and prognostic value of stress cardiovascular magnetic resonance (CMR) in patients with pacemaker (PM). METHODS AND RESULTS: Between 2008 and 2021, we conducted a bi-centre longitudinal study with all consecutive patients with MR-conditional PM referred for vasodilator stress CMR at 1.5 T in the Institut Cardiovasculaire Paris Sud and Lariboisiere University Hospital. They were followed for the occurrence of major adverse cardiovascular events (MACE) defined as cardiac death or non-fatal myocardial infarction. Cox regression analyses were performed to determine the prognostic value of CMR parameters. The quality of CMR was rated by two observers blinded to clinical details. Of 304 patients who completed the CMR protocol, 273 patients (70% male, mean age 71 ± 9 years) completed the follow-up (median [interquartile range], 7.1 [5.4-7.5] years). Among those, 32 experienced a MACE (11.7%). Stress CMR was well tolerated with no significant change in lead thresholds or pacing parameters. Overall, the image quality was rated good or excellent in 84.9% of segments. Ischaemia and late gadolinium enhancement (LGE) were significantly associated with the occurrence of MACE (hazard ratio, HR: 11.71 [95% CI: 4.60-28.2]; and HR: 5.62 [95% CI: 2.02-16.21], both P < 0.001). After adjustment for traditional risk factors, ischaemia and LGE were independent predictors of MACE (HR: 5.08 [95% CI: 2.58-14.0]; and HR: 2.28 [95% CI: 2.05-3.76]; both P < 0.001). CONCLUSION: Stress CMR is safe, feasible and has a good discriminative prognostic value in consecutive patients with PM.

Machine-Learning Score Using Stress CMR for Death Prediction in Patients With Suspected or Known CAD.

BACKGROUND: In patients with suspected or known coronary artery disease, traditional prognostic risk assessment is based on a limited selection of clinical and imaging findings. Machine learning (ML) methods can take into account a greater number and complexity of variables. OBJECTIVES: This study sought to investigate the feasibility and accuracy of ML using stress cardiac magnetic resonance (CMR) and clinical data to predict 10-year all-cause mortality in patients with suspected or known coronary artery disease, and compared its performance with existing clinical or CMR scores. METHODS: Between 2008 and 2018, a retrospective cohort study with a median follow-up of 6.0 (IQR: 5.0-8.0) years included all consecutive patients referred for stress CMR. Twenty-three clinical and 11 stress CMR parameters were evaluated. ML involved automated feature selection by random survival forest, model building with a multiple fractional polynomial algorithm, and 5 repetitions of 10-fold stratified cross-validation. The primary outcome was all-cause death based on the electronic National Death Registry. The external validation cohort of the ML score was performed in another center. RESULTS: Of 31,752 consecutive patients (mean age: 63.7 ± 12.1 years, and 65.7% male), 2,679 (8.4%) died with 206,453 patient-years of follow-up. The ML score (ranging from 0 to 10 points) exhibited a higher area under the curve compared with Clinical and Stress Cardiac Magnetic Resonance score, European Systematic Coronary Risk Estimation score, QRISK3 score, Framingham Risk Score, and stress CMR data alone for prediction of 10-year all-cause mortality (ML score: 0.76 vs Clinical and Stress Cardiac Magnetic Resonance score: 0.68, European Systematic Coronary Risk Estimation score: 0.66, QRISK3 score: 0.64, Framingham Risk Score: 0.63, extent of inducible ischemia: 0.66, extent of late gadolinium enhancement: 0.65; all P < 0.001). The ML score also exhibited a good area under the curve in the external cohort (0.75). CONCLUSIONS: The ML score including clinical and stress CMR data exhibited a higher prognostic value to predict 10-year death compared with all traditional clinical or CMR scores.

Reproducibility of the 2016 American Society of Echocardiography-European Association of Cardiovascular Imaging Algorithm for Estimation of Left Ventricular Filling Pattern: Not Perfect but Good Enough.

The 2016 American Society of Echocardiography (ASE) and European Association of Cardiovascular Imaging (EACVI) guidelines for the evaluation of left ventricular diastolic function reported a new algorithm to assess diastolic function and to estimate left ventricular filling pressure (LVFP). At least five to six different parameters were necessary to conclude, each of them with their own inter-observer variability. This article examines the reproducibility of each parameter of the algorithm and its influence on the final decision of the clinician. Echocardiographic exams of 12 non-selected patients without any known cardiac disease or follow-up but addressed to the hospital for symptoms were analyzed by two readers (one junior and one senior) in five French cardiologic tertiary centers. Inter-observer reproducibility at each step of the algorithm and final decision were analyzed. There was mild agreement on the final decision. The main reasons of discrepancy were disagreement on the significance of mitral annular calcifications and measured values that are just around the cut-off (despite good reproducibility, a slight variation could lead to misclassification of a dichotomous choice between a normal measure and a pathologic measure). Without considering performance, this multicentric French study puts forward limits to the actual algorithm recommended for LVFP pattern assessment. Agreement is excellent in caricatural (easy) cases (left ventricular pressure clearly normal or clearly elevated) but a great discordance exists in the gray zone. Improvement in the algorithm and in the method for LVFP determination is proposed.

TRI-SCORE: a new risk score for in-hospital mortality prediction after isolated tricuspid valve surgery.

AIMS: Isolated tricuspid valve surgery (ITVS) is considered to be a high-risk procedure, but in-hospital mortality is markedly variable. This study sought to develop a dedicated risk score model to predict the outcome of patients after ITVS for severe tricuspid regurgitation (TR). METHODS AND RESULTS: All consecutive adult patients who underwent ITVS for severe non-congenital TR at 12 French centres between 2007 and 2017 were included. We identified 466 patients (60 ± 16 years, 49% female, functional TR in 49%). In-hospital mortality rate was 10%. We derived and internally validated a scoring system to predict in-hospital mortality using multivariable logistic regression and bootstrapping with 1000 re-samples. The final risk score ranged from 0 to 12 points and included eight parameters: age ≥70 years, New York Heart Association Class III-IV, right-sided heart failure signs, daily dose of furosemide ≥125 mg, glomerular filtration rate <30 mL/min, elevated bilirubin, left ventricular ejection fraction <60%, and moderate/severe right ventricular dysfunction. Tricuspid regurgitation mechanism was not an independent predictor of outcome. Observed and predicted in-hospital mortality rates increased from 0% to 60% and from 1% to 65%, respectively, as the score increased from 0 up to ≥9 points. Apparent and bias-corrected areas under the receiver operating characteristic curves were 0.81 and 0.75, respectively, much higher than the logistic EuroSCORE (0.67) or EuroSCORE II (0.63). CONCLUSION: We propose TRI-SCORE as a dedicated risk score model based on eight easy to ascertain parameters to inform patients and physicians regarding the risk of ITVS and guide the clinical decision-making process of patients with severe TR, especially as transcatheter therapies are emerging (www.tri-score.com).

Thromboembolism and bleeding in systemic amyloidosis: a review.

The assessment of both thromboembolic and haemorrhagic risks and their management in systemic amyloidosis have been poorly emphasized so far. This narrative review summarizes main evidence from literature with clinical perspective. The rate of thromboembolic events is as high as 5-10% amyloidosis patients, at least in patients with cardiac involvement, with deleterious impact on prognosis. The most known pro-thrombotic factors are heart failure, atrial fibrillation, and atrial myopathy. Atrial fibrillation could occur in 20% to 75% of systemic amyloidosis patients. Cardiac thrombi are frequently observed in patients, particularly in immunoglobulin light chains (AL) amyloidosis, up to 30%, and it is advised to look for them systematically before cardioversion. In AL amyloidosis, nephrotic syndrome and the use of immunomodulatory drugs also favour thrombosis. On the other hand, the bleeding risk increases because of frequent amyloid digestive involvement as well as factor X deficiency, renal failure, and increased risk of dysautonomia-related fall.

Doxorubicin-induced and trastuzumab-induced cardiotoxicity in mice is not prevented by metoprolol.

AIMS: Our objectives were to validate a murine model of chronic cardiotoxicity induced by Doxorubicin (Dox) and Trastuzumab (Trast) and to test the potential cardio-protective effect of metoprolol. METHODS AND RESULTS: Male C57Bl6 mice were intraperitoneally injected during 2 weeks with Dox (24 mg/kg) or saline, and then with Trast (10 mg/kg) or saline for two more weeks. Half of the mice received metoprolol (100 mg/kg). Cardiotoxicity was defined by a decline in left ventricular ejection fraction (LVEF) ≥ 10 points. At Day 42, Dox + Trast-treated mice exhibited a 13-points decline in LVEF (74 ± 2.6% vs. 87 ± 0.8% for control mice, P < 0.001) and a severe cardiac atrophy (heart weight: 105 ± 2.7 mg vs. 119 ± 3.9 mg for control mice, P < 0.01). This cardiac atrophy resulted from an excess of cardiac necrosis (assessed by plasma cardiac troponin I level: 3.2 ± 0.4 ng/L vs. 1.3 ± 0.06 ng/L for control mice, P < 0.01), an increase in apoptosis (caspase 3 activity showing a six-fold increase for Dox + Trast-treated mice vs. controls, P < 0.001), and cardiomyocyte atrophy (myocyte size: 0.67 ± 0.08 µm2 vs. 1.36 ± 0.10 µm2 for control mice, P < 0.001). In addition, Dox + Trast-treated mice were shown to have an increased cardiac oxidative stress (164 ± 14 dihydroethidine-marked nuclei per area vs. 56 ± 9.5 for control mice, P < 0.01) and increased cardiac fibrosis (the semi-quantitative fibrosis score was three-fold higher for Dox + Trast-treated mice as compared with controls, P < 0.01). Metoprolol was not able to prevent either the decrease in LVEF or the severe cardiac atrophy, the cardiac necrosis, and the cardiac remodelling induced by chemotherapies. CONCLUSION: A murine model of chronic cardiotoxicity induced by Dox and Trast was characterized by a decrease in cardiac function, a cardiac apoptosis and necrosis leading to cardiomyocyte atrophy. Metoprolol did not prevent this cardiotoxicity.

Prognostic value of cardiopulmonary exercise testing in cardiac amyloidosis.

AIMS: In amyloid patients, cardiac involvement dramatically worsens functional capacity and prognosis. We sought to study how the cardiopulmonary exercise test (CPET) could help in functional assessment and risk stratification of patients with cardiac amyloidosis (CA). METHODS AND RESULTS: We carried out a multicentre study including patients with light chain (AL) or transthyretin (TTR) CA. All patients underwent exhaustive examination including CPET and follow-up. The primary prognostic endpoint was the occurrence of death or heart failure hospitalization. Overall, 150 patients were included (91 AL and 59 TTR CA). Median age, systolic blood pressure, N-terminal pro B-type natriuretic peptide (NT-proBNP) and cardiac troponin T were 70 (64-78) years, 121 [interquartile range (IQR) 109-139] mmHg, 2806 (IQR 1218-4638) ng/L and 64 (IQR 33-120) ng/L, respectively. New York Heart Association classes were I-II in 64%. Median peak oxygen consumption (VO2 ) and circulatory power were low at 13.0 (10.0-16.9) mL/kg/min and 1730 (1318-2614) mmHg/mL/min, respectively. The minute ventilation/carbon dioxide production slope was increased to 37 (IQR 33-45). A total of 77 patients (51%) had chronotropic insufficiency. After a median follow-up of 20 months, there were 37 deaths and 44 heart failure hospitalizations. At multivariate Cox analysis, peak VO2 ≤13 mL/kg/min [hazard ratio (HR) 2.7, 95% confidence interval (CI) 1.6-4.8], circulatory power ≤1730 mmHg/mL/min (HR 2.4, 95% CI 1.2-4.6) and NT-proBNP ≥1800 ng/L (HR 2.2, 95% CI 1.1-4.3) were found to be associated with the primary outcome. No events occurred in patients with both peak VO2 >13 mL/kg/min and NT-proBNP <1800 ng/L, while the association of VO2 ≤13 mL/kg/min with NT-proBNP ≥1800 ng/L identified a very high-risk subgroup. CONCLUSION: In CA, CPET is helpful in assessing functional capacity, circulatory and chronotropic responses as well as the prognosis of patients along with cardiac biomarkers.

A simple echocardiographic score to rule out cardiac amyloidosis.

BACKGROUND: Early diagnosis of cardiac amyloidosis (CA) is warranted to initiate specific treatment and improve outcome. The amyloid light chain (AL) and inferior wall thickness (IWT) scores have been proposed to assess patients referred by haematologists or with unexplained left ventricular (LV) hypertrophy, respectively. These scores are composed of 4 or 5 variables, respectively, including strain data. METHODS: Based on 2 variables common to the AL and IWT scores, we defined a simple score named AMYLoidosis Index (AMYLI) as the product of relative wall thickness (RWT) and E/e' ratio, and assessed its diagnostic performance. RESULTS: In the original cohort (n = 251), CA was ultimately diagnosed in 111 patients (44%). The 2.22 value was selected as rule-out cut-off (negative likelihood ratio [LR-] 0.0). In the haematology subset, AL CA was diagnosed in 32 patients (48%), with 2.36 as rule-out cut-off (LR- 0.0). In the hypertrophy subset, ATTR CA was diagnosed in 79 patients (43%), with 2.22 as the best rule-out cut-off (LR- 0.0). In the validation cohort (n = 691), the same cut-offs proved effective: indeed, there were no patients with CA in the whole population or in the haematology or hypertrophy subsets scoring < 2.22, <2.36 or < 2.22, respectively. CONCLUSIONS: The AMYLI score (RWT*E/e') may have a role as an initial screening tool for CA. A < 2.22 value excludes the diagnosis in patients undergoing a diagnostic screening for CA, while a < 2.36 and a < 2.22 value may be better considered in the subsets with suspected cardiac AL amyloidosis or unexplained hypertrophy, respectively.

Delayed acute myocarditis and COVID-19-related multisystem inflammatory syndrome.

Precise descriptions of coronavirus disease 2019 (COVID-19)-related cardiac damage as well as underlying mechanisms are scarce. We describe clinical presentation and diagnostic workup of acute myocarditis in a patient who had developed COVID-19 syndrome 1 month earlier. A healthy 40-year-old man suffered from typical COVID-19 symptoms. Four weeks later, he was admitted because of fever and tonsillitis. Blood tests showed major inflammation. Thoracic computed tomography was normal, and RT-PCR for SARS-CoV-2 on nasopharyngeal swab was negative. Because of haemodynamic worsening with both an increase in cardiac troponin and B-type natriuretic peptide levels and normal electrocardiogram, acute myocarditis was suspected. Cardiac echographic examination showed left ventricular ejection fraction at 45%. Exhaustive diagnostic workup included RT-PCR and serologies for infectious agents and autoimmune blood tests as well as cardiac magnetic resonance imaging and endomyocardial biopsies. Cardiac magnetic resonance with T2 mapping sequences showed evidence of myocardial inflammation and focal lateral subepicardial late gadolinium enhancement. Pathological analysis exhibited interstitial oedema, small foci of necrosis, and infiltrates composed of plasmocytes, T-lymphocytes, and mainly CD163+ macrophages. These findings led to the diagnosis of acute lympho-plasmo-histiocytic myocarditis. There was no evidence of viral RNA within myocardium. The only positive viral serology was for SARS-CoV-2. The patient and his cardiac function recovered in the next few days without use of anti-inflammatory or antiviral drugs. This case highlights that systemic inflammation associated with acute myocarditis can be delayed up to 1 month after initial SARS-CoV-2 infection and can be resolved spontaneously.

Isolated tricuspid valve surgery: impact of aetiology and clinical presentation on outcomes.

AIMS: The aim of this study was to identify determinants of in-hospital and mid-term outcomes after isolated tricuspid valve surgery (ITVS) and more specifically the impact of tricuspid regurgitation (TR) mechanism and clinical presentation. METHODS AND RESULTS: Among 5661 consecutive adult patients who underwent a tricuspid valve (TV) surgery at 12 French tertiary centres in 2007-2017 collected from a mandatory administrative database, we identified 466 patients (8% of all tricuspid surgeries) who underwent an ITVS. Most patients presented with advanced disease [47% in New York Heart Association (NYHA) III/IV, 57% with right-sided heart failure (HF) signs]. Tricuspid regurgitation was functional in 49% (22% with prior left-sided heart valve surgery and 27% isolated) and organic in 51% (infective endocarditis in 31% and other causes in 20%). In-hospital mortality and major complications rates were 10% and 31%, respectively. Rates of survival and survival free of HF readmission were 75% and 62% at 5 years. Patients with functional TR incurred a worse in-hospital mortality than those with organic TR (14% vs. 6%, P = 0.004), but presentation was more severe. Independent determinants of outcomes were NYHA Class III/IV [odd ratios (OR) = 2.7 (1.2-6.1), P = 0.01], moderate/severe right ventricular dysfunction [OR = 2.6 (1.2-5.8), P = 0.02], lower prothrombin time [OR = 0.98 (0.96-0.99), P = 0.008], and with borderline statistical significance, right-sided HF signs [OR = 2.4 (0.9-6.5), P = 0.06] while TR mechanism was not [OR = 0.7 (0.3-1.8), P = 0.88]. CONCLUSION: Isolated TV surgery was associated with high mortality and morbidity, both in hospital and during follow-up, predicted by the severity of the presentation but not by TR mechanism. Our results suggest that TV intervention should be performed earlier in the course of the disease.

Reproducibility of reading echocardiographic parameters to assess severity of mitral regurgitation. Insights from a French multicentre study.

BACKGROUND: Poor reproducibility in assessment of mitral regurgitation (MR) has been reported. AIM: To investigate the robustness of echocardiographic MR assessment in 2019, based on improvements in technology and the skill of echocardiographists regarding MR quantification. METHODS: Reproducibility in parameters of MR severity and global rating were tested using transthoracic echocardiography in 25 consecutive patients independently analysed by 16 junior and senior cardiologists specialized in echocardiography (400 analyses per parameter). RESULTS: Overall interobserver agreement for mechanism definition, effective regurgitant orifice area (EROA) and regurgitant volume (RVol) was moderate, and was lower in secondary MR. Interobserver agreement was substantial for EROA [0.61, 95% confidence interval (CI) 0.45-0.75] and moderate for RVol with the PISA method (0.50, 95% CI 0.33-0.56) in senior physicians and was fair in junior physicians (0.33, 95% CI 0.19-0.51 and 0.36, 95% CI 0.36-0.43, respectively). Using a multiparametric approach, overall interobserver agreement for grading MR severity was fair (0.30), was slightly better in senior than in junior physicians (0.31 vs. 0.28, respectively) with substantial or almost perfect agreement more frequently observed in senior versus junior physicians (52% vs. 36%, respectively). CONCLUSION: Reproducible transthoracic echocardiography MR quantification remains challenging in 2019, despite the expected high skills of echocardiographers regarding MR at the time of dedicated percutaneous intervention. The multiparametric approach does not entirely alleviate the substantial dispersion in measurement of MR severity parameters, whereas reader experience seems to partially address the issue. Our study emphasizes the continuing need for multimodality imaging and education in the evaluation of MR among cardiologists.

[AL amyloidosis, from diagnosis to treatment]. / Amylose AL, du diagnostic au traitement.

Al amyloidosis, from diagnosis to treatment. AL amyloidosis is a rare hemopathy characterized by immunoglobulin light chains deposits in almost all organs causing organ failure. The main issue is the early dia¬gnosis, which must be made in front of an unexplained non-specific symptomatology, especially cardiac or renal, in frequently elderly patients with monoclonal gammo¬pathy. Non-invasive biopsies should be made for histolo¬gical confirmation revealing positive congo red and birefringent yellow-green deposits in polarized light specific for amyloidosis. Severity is assessed by biologi¬cal markers of cardiac involvement. The treatment consists in eliminating the plasma or lympho-plasma cell dyscrasia secreting the amyloidogenic light chain, and in proposing supportive care specific to this pathology.

Amylose al, du diagnostic au traitement. L'amylose AL est une hémopathie rare, caractérisée par des dépôts de chaînes légères d'immunoglobulines, pouvant survenir dans presque tous les organes et pouvant entraîner leur défaillance. L'enjeu principal est le diagnostic précoce qui doit être évoqué devant une symptomatologie souvent aspécifique, surtout cardiaque ou rénale, non expliquée chez des patients fréquemment âgés et porteurs d'une gammapathie monoclonale. Des biopsies non invasives doivent rapidement permettre la confirmation histologique révélant des dépôts positifs au rouge congo et biréfringent jaune-vert en lumière polarisée spécifique de l'amylose. La gravité est évaluée par les marqueurs biologiques d'atteinte cardiaque. Le traitement consiste à éliminer le clone plas¬mocytaire ou lymphoplasmocytaire sécrétant la chaîne lé¬gère amyloïdogène, et à proposer des soins de support spécifiques à cette pathologie.

Diagnostic score of cardiac involvement in AL amyloidosis.

AIMS: Early diagnosis of cardiac involvement is a key issue in the management of AL amyloidosis. Our objective was to establish a diagnostic score of cardiac involvement in AL amyloidosis and to compare it with the current consensus criteria [i.e. left ventricular hypertrophy >12 mm and N-terminal pro b-type natriuretic peptide (NT-proBNP) >332 ng/L]. METHODS AND RESULTS: We carried out a prospective and multicenter study on AL amyloidosis patients who underwent cardiac evaluation including clinical examination, electrocardiography (ECG), cardiac biomarkers, transthoracic echocardiography (TTE), and cardiac magnetic resonance imaging (CMR). Cardiac involvement was based on CMR and/or endomyocardial biopsy. In a derivation cohort of 114 patients (82 with cardiac involvement), the highest diagnostic accuracy was observed with NT-proBNP and troponin blood levels, TTE-derived global longitudinal strain (LS), and apical to basal LS gradient. By using multivariate analysis, we established a diagnostic score including global LS ≥-17% (1 point), apical/(basal + median) LS ≥0.90 (1 point), and troponin T >35 ng/L (1 point). A score >1 was associated with sensitivity of 94% and specificity of 97%, an area under the curve of 0.98 [95% confidence interval (CI) 0.93-0.99] as well as a net reclassification index of 0.39 (95% CI 0.28-0.46) when compared with consensus criteria. In a validation cohort of 73 AL amyloidosis patients, the area under the receiver operating characteristic curve of the diagnostic score was 0.97 (95% CI 0.90-0.99). CONCLUSION: Combining T troponin blood levels and two echo-derived strain parameters leads to very high accuracy for diagnosing cardiac involvement in AL amyloid patients.

Subclinical Left Ventricular Dysfunction During Chemotherapy.

Subclinical left ventricular dysfunction is the most common cardiac complication after chemotherapy administration. Detection and early treatment are major issues for better cardiac outcomes in this cancer population. The most common definition of cardiotoxicity is a 10-percentage point decrease of left ventricular ejection fraction (LVEF) to a value <53%. The myocardial injury induced by chemotherapies is probably a continuum starting with cardiac biomarkers increase before the occurence of a structural myocardial deformation leading to a LVEF decline. An individualised risk profile (depending on age, cardiovascular risk factors, type of chemotherapy, baseline troponin, baseline global longitudinal strain and baseline LVEF) has to be determined before starting chemotherapy to consider cardioprotective treatment. To date, there is no proof of a systematic cardioprotective treatment (angiotensin-converting enzyme inhibitor and/or beta-blocker) in all cancer patients. However, early cardioprotective treatment in case of subclinical left ventricular dysfunction seems to be promising in the prevention of cardiac events.