Description of the two dimensional layer-specific strain echocardiography phenotype of arrhythmogenic left ventricular cardiomyopathy.

BACKGROUND: Arrhythmogenic left ventricular cardiomyopathy (ALVC) is characterized by fibrofatty myocardial replacement evidenced on cardiac magnetic resonance (CMR) by late gadolinium enhancement (LGE) mainly involving subepicardium. The study aimed to describe the layer-specific strain (LSS) echocardiography phenotype of ALVC and to compare it to LGE features. METHODS: All consecutive ALVC pathogenic genetic variant carriers and non-carrier relatives were reparted in four pre-specified groups (overt ALVC (Group 1), isolated LGE (Group 2), pathogenic genetic variant carrier without ALVC phenotype (Group 3), no genetic variant carrier (Group 4)) and explored accordingly by CMR and LSS echocardiography. RESULTS: Eighty-five individuals were included. Endocardial global longitudinal strain (GLS) (GLSendo)-Epicardial GLS (GLSepi) gradient was predominantly altered in Group 1 illustrating transmural strain alteration in overt ALVC (3.8 ± 1.1 in Group 1, 4.3 ± 2.2 in Group 2, 5.2 ± 1.2 in Group 3, 5.4 ± 1.6 in Group 4, p=0.0017), whereas GLSepi was predominantly impaired in Group 2 (GLSendo, GLSepi = 15.0 ± 4.1%, 11.2 ± 3.3% respectively in Group 1, 20.5 ± 2.8%, 16.2 ± 5.5% in Group 2, 23.4 ± 3.3%, 18.2 ± 2.7% in Group 3, 24.6 ± 2.8%, 19.2 ± 1.9% in Group 4, all p<0.0001). GLSepi was able to detect subepicardial LGE in genetic variant carriers without overt ALVC with an area under curve (AUC) of 0.84 (0.73;0.95). However, segmental epicardial and endocardial strain behaved similarly and showed comparable diagnostic values for segmental LGE detection (AUC 0.72 (CI 0.69-0.76) and 0.73 (CI 0.70-0.76) respectively, p =0.4). CONCLUSION: LSS alteration in ALVC progresses from epicardium to endocardium along with disease severity. Irrespective of LSS analysis, that did not provide incremental diagnostic value for the detection and localization of LGE, strain echocardiography was shown to be a potential surrogate marker of LGE, including in apparently healthy individuals with isolated LV fibrosis.

Patterns of left ventricular remodeling post-myocardial infarction, determinants, and outcome.

AIM: Left ventricular remodeling (LVR) after myocardial infarction (MI) can lead to heart failure, arrhythmia, and death. We aim to describe adverse LVR patterns at 6 months post-MI and their relationships with subsequent outcomes and to determine baseline. METHODS AND RESULTS: A multicenter cohort of 410 patients (median age 57 years, 87% male) with reperfused MI and at least 3 akinetic LV segments on admission was analyzed. All patients had transthoracic echocardiography performed 4 days and 6 months post-MI, and 214 also had cardiac magnetic resonance imaging performed on day 4. To predict LVR, machine learning methods were employed in order to handle many variables, some of which may have complex interactions. Six months post-MI, echocardiographic increases in LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and LV ejection fraction (LVEF) were 14.1% [interquartile range 0.0, 32.0], 5.0% [- 14.0, 25.8], and 8.7% [0.0, 19.4], respectively. At 6 months, ≥ 15% or 20% increases in LVEDV were observed in 49% and 42% of patients, respectively, and 37% had an LVEF < 50%. The rate of death or new-onset HF at the end of 5-year follow-up was 8.8%. Baseline variables associated with adverse LVR were determined best by random forest analysis and included stroke volume, stroke work, necrosis size, LVEDV, LVEF, and LV afterload, the latter assessed by Ea or Ea/Ees. In contrast, baseline clinical and biological characteristics were poorly predictive of LVR. After adjustment for predictive baseline variables, LV dilation > 20% and 6-month LVEF < 50% were significantly associated with the risk of death and/or heart failure: hazard ratio (HR) 2.12 (95% confidence interval (CI) 1.05-4.43; p = 0.04) and HR 2.68 (95% CI 1.20-6.00; p = 0.016) respectively. CONCLUSION: Despite early reperfusion and cardioprotective therapy, adverse LVR remains frequent after acute MI and is associated with a risk of death and HF. A machine learning approach identified and prioritized early variables that are associated with adverse LVR and which were mainly hemodynamic, combining LV volumes, estimates of systolic function, and afterload.

Chronic heart failure with reduced EF: A decade of major pharmacological innovations.

BACKGROUND AND OBJECTIVES: Because of its severity, prevalence, and medical economic importance, heart failure is a chronic disease that is the subject of intense medical research. The aim of this article was to review the therapeutic innovations of the last decade that have been incorporated into the latest international recommendations for the treatment of heart failure. METHOD: Review of literature and current guidelines. CONCLUSION: The results of the clinical trials reviewed here represent major advances that will have a significant impact on quality of life, survival, rehospitalisation and, for certain treatments, a beneficial joint effect on commonly associated comorbidities such as diabetes and chronic renal failure.

Repurposing the ß3-Adrenergic Receptor Agonist Mirabegron in Patients With Structural Cardiac Disease: The Beta3-LVH Phase 2b Randomized Clinical Trial.

Importance: Left ventricular (LV) hypertrophy contributes to the onset and progression of heart failure (HF), particularly for patients with pre-HF (stage B) for whom no treatment has yet proven effective to prevent transition to overt HF (stage C). The ß3-adrenergic receptors (ß3ARs) may represent a new target, as their activation attenuates LV remodeling. Objective: To determine whether activation of ß3ARs by repurposing a ß3AR agonist, mirabegron, is safe and effective in preventing progression of LV hypertrophy and diastolic dysfunction among patients with pre- or mild HF. Design, Setting, and Participants: The Beta3-LVH prospective, triple-blind, placebo-controlled phase 2b randomized clinical trial enrolled patients between September 12, 2016, and February 26, 2021, with a follow-up of 12 months. The trial was conducted at 10 academic hospitals in 8 countries across Europe (Germany, Poland, France, Belgium, Italy, Portugal, Greece, and the UK). Patients aged 18 years or older with or without HF symptoms (maximum New York Heart Association class II) were screened for the presence of LV hypertrophy (increased LV mass index [LVMI] of ≥95 g/m2 for women or ≥115 g/m2 for men) or maximum wall thickness of 13 mm or greater using echocardiography. Data analysis was performed in August 2022. Intervention: Participants were randomly assigned (1:1) to mirabegron (50 mg/d) or placebo, stratified by the presence of atrial fibrillation and/or type 2 diabetes, for 12 months. Main Outcomes and Measures: The primary end points were LVMI determined using cardiac magnetic resonance imaging and LV diastolic function (early diastolic tissue Doppler velocity [E/e'] ratio assessed using Doppler echocardiography) at 12 months. Patients with at least 1 valid measurement of either primary end point were included in the primary analysis. Safety was assessed for all patients who received at least 1 dose of study medication. Results: Of the 380 patients screened, 296 were enrolled in the trial. There were 147 patients randomized to mirabegron (116 men [79%]; mean [SD] age, 64.0 [10.2] years) and 149 to placebo (112 men [75%]; mean [SD] age, 62.2 [10.9] years). All patients were included in the primary intention-to-treat analysis. At 12 months, the baseline and covariate-adjusted differences between groups included a 1.3-g/m2 increase in LVMI (95% CI, -0.15 to 2.74; P = .08) and a -0.15 decrease in E/e' (95% CI, -0.69 to 0.4; P = .60). A total of 213 adverse events (AEs) occurred in 82 mirabegron-treated patients (including 31 serious AEs in 19 patients) and 215 AEs occurred in 88 placebo-treated patients (including 30 serious AEs in 22 patients). No deaths occurred during the trial. Conclusions: In this study, mirabegron therapy had a neutral effect on LV mass or diastolic function over 12 months among patients who had structural heart disease with no or mild HF symptoms. Trial Registration: ClinicalTrials.gov Identifier: NCT02599480.

Two-Year Outcomes for Tricuspid Repair With a Transcatheter Edge-to-Edge Valve Repair From the Transatlantic TRILUMINATE Trial.

BACKGROUND: Tricuspid regurgitation (TR) is a common and progressive valve disease with significant mortality and hospitalization burden. Tricuspid transcatheter edge-to-edge repair provides a treatment option for high-risk patients with primary and secondary TR. METHODS: The TRILUMINATE trial ([Trial to Evaluate Treatment With Abbott Transcatheter Clip Repair System in Patients With Moderate or Greater Tricuspid Regurgitation]; n=85) is an international, prospective, single-arm, multicenter study to investigate the safety and performance of tricuspid transcatheter edge-to-edge repair with the TriClip implant in patients with symptomatic moderate or greater TR. Echocardiographic assessment was performed at a core laboratory. Outcomes included safety and clinical effectiveness and echocardiographic assessment of TR. RESULTS: At 2 years, TR was reduced to moderate or less in 60% of subjects, and reduction of at least 1 grade was achieved in 85.4% of subjects. TR reduction was sustained in 75% of the patients. While most metrics suggest the majority of favorable remodeling occurred within the first 30 days post-procedure, both right ventricular end diastolic diameter and tricuspid annular plane systolic excursion show signals of continued favorable remodeling through 2 years. Substantial improvements in 6-minute walking distance, New York Heart Association functional class, and Kansas City Cardiomyopathy Questionnaire score were sustained from 30 days to 2 years. Even with low rates of cardiovascular mortality (15.3%) and all-cause mortality (18.7%) noted at 2 years, all-cause hospitalization rate decreased from 1.30 events per patient-year 1 year before device implantation to 0.66 events per patient-year 2 years after the TriClip procedure, representing a reduction of 49% (P<0.0001). CONCLUSIONS: Tricuspid transcatheter edge-to-edge repair using the TriClip implant was found to be safe and effective, with sustained benefits at 2 years in subjects with symptomatic moderate or greater TR. Repair efficacy was durable at 2 years in 75% of the patients. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03227757.

Atrial Fibrillation Burden and Atrial Shunt Therapy in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Atrial fibrillation (AF) is a common comorbidity in patients with heart failure with preserved ejection fraction (HFpEF) and in heart failure with mildly reduced ejection fraction (HFmrEF). OBJECTIVES: This study sought to describe AF burden and its clinical impact among individuals with HFpEF and HFmrEF who participated in a randomized clinical trial of atrial shunt therapy (REDUCE LAP-HF II [A Study to Evaluate the Corvia Medical, Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure]) and to evaluate the effect of atrial shunt therapy on AF burden. METHODS: Study investigators characterized AF burden among patients in the REDUCE LAP-HF II trial by using ambulatory cardiac patch monitoring at baseline (median patch wear time, 6 days) and over a 12-month follow-up (median patch wear time, 125 days). The investigators determined the association of baseline AF burden with long-term clinical events and examined the effect of atrial shunt therapy on AF burden over time. RESULTS: Among 367 patients with cardiac monitoring data at baseline and follow-up, 194 (53%) had a history of AF or atrial flutter (AFL), and median baseline AF burden was 0.012% (IQR: 0%-1.3%). After multivariable adjustment, baseline AF burden ≥0.012% was significantly associated with heart failure (HF) events (HR: 2.00; 95% CI: 1.17-3.44; P = 0.01) both with and without a history of AF or AFL (P for interaction = 0.68). Adjustment for left atrial reservoir strain attenuated the baseline AF burden-HF event association (HR: 1.71; 95% CI: 0.93-3.14; P = 0.08). Of the 367 patients, 141 (38%) had patch-detected AF during follow-up without a history of AF or AFL. Atrial shunt therapy did not change AF incidence or burden during follow-up. CONCLUSIONS: In HFpEF and HFmrEF, nearly 40% of patients have subclinical AF by 1 year. Baseline AF burden, even at low levels, is associated with HF events. Atrial shunt therapy does not affect AF incidence or burden. (A Study to Evaluate the Corvia Medical, Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure [REDUCE LAP-HF II]; NCT03088033).

Clinical features and outcomes of patients admitted to the ICU for Cyclophosphamide-associated cardiac toxicity: a retrospective cohort.

PURPOSE: To describe the management and outcome of critically-ill patients with Cyclophosphamide (CY)-associated cardiac toxicity. METHODS: All patients admitted to the intensive care units (ICUs) of the Nantes and Rennes University Hospitals for a CY-associated cardiac toxicity between January 2015 and December 2020 were included. RESULTS: Of the thirty-four patients included in the study, twenty-four (70%) underwent allogeneic hematopoietic stem cell transplantation (HSCT), four (12%) autologous HSCT, and six (18%) chemotherapy for hematological malignancies. Acute pulmonary edema (65%), cardiac arrest (9%), and cardiac arrhythmia (6%) were the most common reasons for ICU admission. Patients were admitted to the ICU 6.5 (4-12) days after the intravenous administration of a median dose of CY of 100 [60-101] mg/Kg. Echocardiographic findings showed moderate to severe left ventricular systolic dysfunction (69%) and pericardial effusion (52%). Eighteen (53%) patients ultimately developed cardiogenic shock and required vasopressors (47%) and/or inotropes (18%). Invasive mechanical ventilation and renal replacement therapy were required in twenty (59%) and five (14%) patients, respectively. Sixteen (47%) patients died of whom 12 (35.3%) died from refractory cardiogenic shock. The left ventricular ejection fraction improved over time in most survivors with a median time until full recovery of 33 (12-62) days. Two (11%) patients had a persistent left ventricular dysfunction at 6 months. CONCLUSION: Refractory cardiogenic shock is the primary cause of death of patients with severe CY-related cardiotoxicity. Nonetheless, the cardiac function of most survivors recovered within a month.

Prognostic impact of precipitated cardiac decompensation in symptomatic heart failure with reduced ejection fraction and severe secondary mitral regurgitation.

BACKGROUND: Our aim was to assess the distribution of primary (with no trigger) and secondary (with a decompensation trigger) heart failure events in a severe heart failure population and their association with 2-year all-cause mortality in the Mitra.Fr study. METHODS: We included 304 patients with symptomatic heart failure, and severe mitral regurgitation and guideline directed medical therapy randomized to medical therapy alone or medical therapy with percutaneous mitral valve repair. According to the follow-up, we defined 3 categories of events: follow-up without any heart failure event, at least 1 decompensation starting with a primary heart failure decompensation or starting with a precipitated secondary heart failure event. The primary outcome was 2-years all-cause mortality. RESULTS: A total of 179 patients (59 %) had at least 1 heart failure decompensation within 24-months of follow-up. 129 heart failure decompensations (72%) were a first primary heart failure and 50 (28%) were a first secondary decompensation. Finally, 30 patients had both types of decompensations but these were not taken into account for the comparison of primary and secondary decompensations. Primary decompensations were 3-times more frequent than secondary decompensations, but the mean number of heart failure decompensations was similar in the "Primary heart failure group" compared to the "Secondary heart failure group": (1.94 ± 1.39 vs 1.80 ± 1.07 respectively; P = .480). Compared to patients without heart failure decompensation, patients with "Only primary decompensation" or with "Only secondary decompensation" had a significantly increased risk of death (HR = 4.87, 95% CI [2.86, 8.32] and 2.68 95%CI [1.64, 4.37] respectively). All-cause mortality, was not significantly different between these 2 type of decompensations (HR = 1.82, 95% CI [0.93, 3.58]; P = .082), but each additional heart failure recurrence was associated with a significant increase in mortality risk (HR = 1.27, 95% CI [1.08; 1.50]; P = .005). CONCLUSIONS: In heart failure with reduced ejection fraction and severe secondary mitral regurgitation patients, primary heart failure decompensations were 3-times more frequent compared to precipitated decompensations with a nonsignificant trend in increased risk of all-cause mortality. Our results fail to support the differentiation between primary and secondary decompensations as they seem to portend the same outcome impact.

Machine Learning-Based Phenogrouping in MVP Identifies Profiles Associated With Myocardial Fibrosis and Cardiovascular Events.

BACKGROUND: Structural changes and myocardial fibrosis quantification by cardiac imaging have become increasingly important to predict cardiovascular events in patients with mitral valve prolapse (MVP). In this setting, it is likely that an unsupervised approach using machine learning may improve their risk assessment. OBJECTIVES: This study used machine learning to improve the risk assessment of patients with MVP by identifying echocardiographic phenotypes and their respective association with myocardial fibrosis and prognosis. METHODS: Clusters were constructed using echocardiographic variables in a bicentric cohort of patients with MVP (n = 429, age 54 ± 15 years) and subsequently investigated for their association with myocardial fibrosis (assessed by cardiac magnetic resonance) and cardiovascular outcomes. RESULTS: Mitral regurgitation (MR) was severe in 195 (45%) patients. Four clusters were identified: cluster 1 comprised no remodeling with mainly mild MR, cluster 2 was a transitional cluster, cluster 3 included significant left ventricular (LV) and left atrial (LA) remodeling with severe MR, and cluster 4 included remodeling with a drop in LV systolic strain. Clusters 3 and 4 featured more myocardial fibrosis than clusters 1 and 2 (P < 0.0001) and were associated with higher rates of cardiovascular events. Cluster analysis significantly improved diagnostic accuracy over conventional analysis. The decision tree identified the severity of MR along with LV systolic strain <21% and indexed LA volume >42 mL/m2 as the 3 most relevant variables to correctly classify participants into 1 of the echocardiographic profiles. CONCLUSIONS: Clustering enabled the identification of 4 clusters with distinct echocardiographic LV and LA remodeling profiles associated with myocardial fibrosis and clinical outcomes. Our findings suggest that a simple algorithm based on only 3 key variables (severity of MR, LV systolic strain, and indexed LA volume) may help risk stratification and decision making in patients with MVP. (Genetic and Phenotypic Characteristics of Mitral Valve Prolapse, NCT03884426; Myocardial Characterization of Arrhythmogenic Mitral Valve Prolapse [MVP STAMP], NCT02879825).

Perioperative Iron Deficiency in Patients Scheduled for Major Elective Surgeries: A French Prospective Multicenter Cross-Sectional Study.

BACKGROUND: The management of perioperative iron deficiency is a component of the concept of patient blood management. The objective of this study was to update French data on the prevalence of iron deficiency in patients scheduled for major surgery. METHODS: The CARENFER PBM study was a prospective cross-sectional study in 46 centers specialized in orthopedic, cardiac, urologic/abdominal, or gynecological surgery. The primary end point was the prevalence of iron deficiency at the time of surgery (D-1/D0) defined as serum ferritin <100 µg/L and/or transferrin saturation (TSAT) <20%. RESULTS: A total of 1494 patients (mean age, 65.7 years; women, 49.3%) were included from July 20, 2021 to January 3, 2022. The prevalence of iron deficiency in the 1494 patients at D-1/D0 was 47.0% (95% confidence interval [CI], 44.5-49.5). At 30 days after surgery, the prevalence of iron deficiency was 45.0% (95% CI, 42.0-48.0) in the 1085 patients with available data. The percentage of patients with anemia and/or iron deficiency increased from 53.6% at D-1/D0 to 71.3% at D30 ( P < .0001), mainly due to the increase of patients with both anemia and iron deficiency (from 12.2% at D-1/D0 to 32.4% at D30; P < .0001). However, a treatment of anemia and/or iron deficiency was administered preoperatively to only 7.7% of patients and postoperatively to 21.7% (intravenous iron, 14.2%). CONCLUSIONS: Iron deficiency was present in half of patients scheduled for major surgery. However, few treatments to correct iron deficiency were implemented preoperatively or postoperatively. There is an urgent need for action to improve these outcomes, including better patient blood management.

Feasibility and accuracy of linking a heart failure registry to the national claims database using indirect identifiers.

BACKGROUND: Heart failure (HF) registries include rich data on patient inclusion characteristics, but follow-up information is often incomplete. Medicoadministrative databases may provide less clinical information than registries, e.g. on left ventricular ejection fraction (LVEF), but long-term data are exhaustive and reliable. The combination of the two types of database is therefore appealing, but the feasibility and accuracy of such linking are largely unexplored. AIMS: To assess the feasibility and accuracy of linking an HF registry (FRESH; FREnch Survey on Heart Failure) with the French National Healthcare System database (SNDS). METHODS: A probabilistic algorithm was developed to link and match patient data included in the FRESH HF registry with anonymized records from the SNDS, which include: hospitalizations and diagnostic codes; all care-related reimbursements by national health system; and deaths. Consistency was assessed between deaths recorded in the registry and in the SNDS. A comparison between the two databases was carried out on several identifiable clinical characteristics (history of HF hospitalization, diabetes, atrial fibrillation, chronic bronchopneumopathy, severe renal failure and stroke) and on events during 1-year follow-up after inclusion. RESULTS: Of 2719 patients included in the FRESH registry (1049 during decompensation; 1670 during outpatient follow-up), 1885 could be matched with a high accuracy of 94.3% for deaths. Mortality curves were superimposable, including curves according to type of HF and LVEF. The rates of missing data in the FRESH registry were 2.3-8.4% for clinical characteristics and 17.5% for hospitalizations during follow-up. The discrepancy rate for clinical characteristics was 3-13%. Hospitalization rates were significantly higher in the SNDS than in the registry cohort. CONCLUSIONS: The anonymous matching of an HF research cohort with a national health database is feasible, with a significant proportion of patients being accurately matched, and facilitates combination of clinical data and a reduced rate of losses to follow-up.

Renal function decline and heart failure hospitalisation in patients with type 2 diabetes: Dynamic predictions from the prospective SURDIAGENE cohort.

AIMS: For type 2 diabetes persons, we assessed the association between renal function decline and heart failure hospitalisation (HFH) and validated dynamic HFH predictions (DynHFH) based on repeated estimated Glomerular Filtration Rate (eGFR) values. METHODS: We studied 1413 patients from the SURDIAGENE cohort. From a joint model for longitudinal CKD-EPI measures and HFH risk, we calculated the probability of being HFH-free in the next five years. RESULTS: The mean eGFR decline was estimated at 1.48 ml/min/1.73 m2 per year (95 % CI from 1.23 to 1.74). We observed that eGFR decline was significantly associated with the HFH risk (adjHR = 1.15 for an increase in yearly decline of 1 ml/min/1.73 m2, 95 % CI from 1.03 to 1.26) independently of 7 baseline variables (from clinical, biological and ECG domains). Discrimination was good along the prediction times: AUC at 0.87 (95 %CI from 0.84 to 0.91) at patient inclusion and 0.77 (95 %CI from 0.67 to 0.87) at seven years' follow-up. CONCLUSIONS: Renal function decline was significantly associated with the HFH risk. In the era of computer-assisted medical decisions, the DynHFH, a tool that dynamically predicts HFH in type 2 diabetes persons (https://shiny.idbc.fr/DynHFH), might be helpful for precision medicine and the implementation of stratified medical decision-making.

Impact of procedural success on clinical outcome after MitraClip: Results from the MITRA-FR trial.

BACKGROUND: Differences in procedural success rates have been proposed to explain the divergent results between the MITRA-FR trial (Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation) and the COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation). AIM: To examine whether MITRA-FR patients who had successful clip implantation achieved a better outcome than the control group. METHODS: Based on the per protocol population of MITRA-FR, we compared the outcome in 71 patients in whom optimal clip implantation was achieved (group 1: mitral regurgitation grade ≤ 1 + at discharge) with that in 23 patients with non-optimal clip implantation (group 2: mitral regurgitation grade ≥ 2 + at discharge) and that in 137 patients in the control group (group 3). The primary endpoint was all-cause death or unplanned hospitalization for heart failure at 24 months. RESULTS: Event-free survival was not different across the groups (42±6% in group 1, 30±10% in group 2 and 31±4% in group 3; log-rank P=0.32). In multivariable analyses, after adjustment for age, sex, rhythm, aetiology, left ventricular ejection fraction and mitral regurgitation severity, group was not associated with variations in outcome: using Group 3 as reference, hazard ratio 0.86, 95% confidence interval 0.58-1.27 (P=0.43) in group 1; and hazard ratio 0.98 95% confidence interval 0.54-1.76 (P=0.94) in group 2. CONCLUSIONS: The clinical outcome of patients in whom optimal procedural result was achieved at discharge was not different compared with the control group. Our results do not support the hypothesis that the differences in rates of residual mitral regurgitation at discharge between MITRA-FR and COAPT explain the divergent results between the two trials.

Acute Myocarditis Associated With Desmosomal Gene Variants.

BACKGROUND: The risk of adverse cardiovascular events in patients with acute myocarditis (AM) and desmosomal gene variants (DGV) remains unknown. OBJECTIVES: The purpose of this study was to ascertain the risk of death, ventricular arrhythmias, recurrent myocarditis, and heart failure (main endpoint) in patients with AM and pathogenic or likely pathogenetic DGV. METHODS: In a retrospective international study from 23 hospitals, 97 patients were included: 36 with AM and DGV (DGV[+]), 25 with AM and negative gene testing (DGV[-]), and 36 with AM without genetics testing. All patients had troponin elevation plus findings consistent with AM on histology or at cardiac magnetic resonance (CMR). In 86 patients, CMR changes in function and structure were re-assessed at follow-up. RESULTS: In the DGV(+) AM group (88.9% DSP variants), median age was 24 years, 91.7% presented with chest pain, and median left ventricular ejection fraction (LVEF) was 56% on CMR (P = NS vs the other 2 groups). Kaplan-Meier curves demonstrated a higher risk of the main endpoint in DGV(+) AM compared with DGV(-) and without genetics testing patients (62.3% vs 17.5% vs 5.3% at 5 years, respectively; P < 0.0001), driven by myocarditis recurrence and ventricular arrhythmias. At follow-up CMR, a higher number of late gadolinium enhanced segments was found in DGV(+) AM. CONCLUSIONS: Patients with AM and evidence of DGV have a higher incidence of adverse cardiovascular events compared with patients with AM without DGV. Further prospective studies are needed to ascertain if genetic testing might improve risk stratification of patients with AM who are considered at low risk.

Nutritional biomarkers and heart failure requiring hospitalization in patients with type 2 diabetes: the SURDIAGENE cohort.

BACKGROUND: Heart failure (HF) is a growing complication and one of the leading causes of mortality in people living with type 2 diabetes (T2D). Among the possible causes, the excess of red meat and the insufficiency of vegetables consumption are suspected. Such an alimentation is associated with nutritional biomarkers, including trimethylamine N-oxide (TMAO) and its precursors. Here, we aimed to study these biomarkers as potential prognostic factors for HF in patients with T2D. METHODS: We used the SURDIAGENE (SURvival DIAbetes and GENEtics) study, a large, prospective, monocentric cohort study including 1468 patients with T2D between 2001 and 2012. TMAO and its precursors (trimethylamine [TMA], betaine, choline, and carnitine) as well as thio-amino-acids (cysteine, homocysteine and methionine) were measured by liquid chromatography-tandem mass spectrometry. The main outcome was HF requiring Hospitalization (HFrH) defined as the first occurrence of acute HF leading to hospitalization and/or death, established by an adjudication committee, based on hospital records until 31st December 2015. The secondary outcomes were the composite event HFrH and/or cardiovascular death and all-cause death. The association between the biomarkers and the outcomes was studied using cause-specific hazard-models, adjusted for age, sex, history of coronary artery disease, NT-proBNP, CKD-EPI-derived eGFR and the urine albumin/creatinine ratio. Hazard-ratios (HR) are expressed for one standard deviation. RESULTS: The data of interest were available for 1349/1468 of SURDIAGENE participants (91.9%), including 569 (42.2%) women, with a mean age of 64.3 ± 10.7 years and a median follow-up of 7.3 years [25th-75th percentile, 4.7-10.8]. HFrH was reported in 209 patients (15.5%), HFrH and/or cardiovascular death in 341 (25.3%) and all-cause death in 447 (33.1%). In unadjusted hazard-models, carnitine (HR = 1.20, 95% CI [1.05; 1.37]), betaine (HR = 1.34, [1.20; 1.50]), choline (HR = 1.35, [1.20; 1.52]), TMAO (HR = 1.32, [1.16; 1.50]), cysteine (HR = 1.38, [1.21; 1.58]) and homocysteine (HR = 1.28, [1.17; 1.39]) were associated with HFrH, but not TMA and methionine. In the fully adjusted models, none of these associations was significant, neither for HFrH nor for HFrH and/or CV death, when homocysteine only was positively associated with all-cause death (HR = 1.16, [1.06; 1.27]). CONCLUSIONS: TMAO and its precursors do not appear to be substantial prognosis factors for HFrH, beyond usual cardiac- and kidney-related risk factors, whereas homocysteine is an independent risk factor for all-cause death in patients with T2D.

Amylose cardiaque dite sénile : diagnostic et nouvelles perspectives thérapeutiques.

Résumé L'amylose cardiaque dite sénile, également dénommée « sauvage ¼, était considérée comme une maladie rare. Actuellement, grâce à des moyens diagnostiques non invasifs et à partir d'études autopsiques, nous estimons la prévalence à environ 10 à 20 % des sujets de plus de 80 ans. De même, l'amylose était un diagnostic sans conséquence thérapeutique, mis à part le traitement de l'insuffisance cardiaque et des troubles de conduction. De nouveaux traitements permettent de stabiliser le tétramère de transthyrétine et de diminuer la production d'oligomères, sources des dépôts d'amylose, en cas de formes héréditaires et sauvage d'amylose à transthyrétine. Deux médicaments bloquant la production de transthyrétine (anti-sens et oligonucléotides) sont également en phase d'essais cliniques dans les amyloses cardiaques. Ainsi, le diagnostic et la prise en charge de l'amylose cardiaque deviennent des démarches diagnostiques de pratique clinique et doivent être connus des cardiologues, mais également des gériatres qui permettront une prise en charge précoce et donc plus efficace. Abstract So-called senile cardiac amyloidosis was considered rare. Nowadays, thanks to non-invasive diagnostic means and autopsy studies, we estimate the prevalence to be about 20% of subjects over 75 years of age. Similarly, amyloidosis was a diagnosis with no therapeutic consequences, apart from the treatment of heart failure and conduction disorders. New treatments make it possible to stabilise the transthyretin tetramer and to reduce the production of oligomers that are the source of amyloid deposits, by acting in a non-genetic way and therefore adapted to the "wild" transthyretin forms of so-called senile cardiac amyloidosis. Thus, the diagnosis and management of cardiac amyloidosis are becoming diagnostic procedures in clinical practice and must be known by cardiologists, but also by geriatricians, who will allow early and therefore more effective management.

Delayed hospitalisation for heart failure after transcatheter repair or medical treatment for secondary mitral regurgitation: a landmark analysis of the MITRA-FR trial.

BACKGROUND: In the MITRA-FR trial, transcatheter mitral valve repair (TMVR) was not associated with a 2-year clinical benefit in patients with secondary mitral regurgitation (SMR). AIMS: This landmark analysis aimed at investigating a potential reduction of the hospitalisation rate for heart failure (HF) between 12 and 24 months after inclusion in the MITRA-FR trial in patients randomised to the intervention group (TMVR with the MitraClip device), as compared with patients randomised to the control group (guideline-directed medical therapy [GDMT]). METHODS: The MITRA-FR trial randomised 307 patients with SMR for TMVR on top of GDMT (TMVR group; n=152) or for GDMT alone (control group; n=155). We conducted a 12-month landmark analysis in surviving patients who were not hospitalised for HF within the first 12 months of follow-up. The primary endpoint was the 1-year cumulative number of HF hospitalisations. RESULTS: A total of 140 patients (TMVR group: 67; GDMT group: 73) were selected for this landmark analysis with similar characteristics at inclusion in the trial. The primary endpoint was 28 events per 100 patient-years in the TMVR group, as compared with 60 events per 100 patient-years in the GDMT group (hazard ratio [HR] 0.46, 95% confidence interval [CI]: 0.20-1.02; p=0.057). CONCLUSIONS: In this landmark analysis of the MITRA-FR trial, the cumulative rate of HF hospitalisation between 12 and 24 months among patients treated with TMVR on top of GDMT was approximately half as many as those of patients treated with GDMT alone, a difference which did not reach statistical significance in the setting of a low number of events.

Iron deficiency screening is a key issue in chronic inflammatory diseases: A call to action.

Iron deficiency is frequent in patients with chronic inflammatory conditions (e.g., chronic heart failure, chronic kidney disease, cancers, and bowel inflammatory diseases). Indeed, high concentrations of inflammatory cytokines increase hepcidin concentrations that lead to the sequestration of iron in cells of the reticuloendothelial system (functional iron deficiency). Iron parameters are often assessed only in the context of anemia, but iron deficiency, even without anemia, is present in about half of patients with inflammatory conditions. Iron deficiency worsens underlying chronic diseases and is an independent factor of morbidity and mortality. In daily practice, the most effective biomarkers of iron status are serum ferritin, which reflects iron storage, and transferrin saturation, which reflects the transport of iron. Serum ferritin is increased in an inflammatory context, and there is still no consensus on the threshold to be used in chronic inflammatory conditions. Nevertheless, recent recommendations of international guidelines agreed to define iron deficiency by serum ferritin <100 µg/L and/or transferrin saturation <20%. Iron parameters remain, however, insufficiently assessed in patients with chronic inflammatory conditions. Indeed, clinical symptoms of iron deficiency, such as fatigue, are not specific and often confused with those of the primary disease. Iron repletion, preferably by the intravenous route to bypass tissue sequestration, improves clinical signs and quality of life. Because of the negative impact of iron deficiency on chronic inflammatory diseases and the efficacy of intravenous iron repletion, screening of iron parameters should be part of the routine examination of all patients with chronic inflammatory diseases.

Iron Deficiency in Patients with Inflammatory Bowel Diseases: A Prospective Multicenter Cross-Sectional Study.

BACKGROUND: Iron deficiency (ID) is a frequent condition in patients with inflammatory bowel disease (IBD). AIM: Our aim was to investigate the prevalence of ID in patients with IBD. METHODS: This was a prospective multicenter cross-sectional study conducted in 21 gastroenterology departments in France between January and March 2020. All adult patients with confirmed IBD who were admitted to the hospital were eligible for inclusion. ID was defined as ferritinemia ≤ 100 µg/L in patients with signs of inflammation (C-reactive protein (CRP) ≥ 5 mg/L) or ferritinemia < 30 µg/L in the absence of inflammation. RESULTS: In total, 1036 IBD (685 Crohn's disease and 351 ulcerative colitis) patients (52.1% women) with a mean age of 41.8 ± 15.5 years were recruited. Approximately half of the patients (504, 51.1%) were in disease remission at the time of enrollment. Systematic monitoring of iron status was performed in 12/21 (57%) participating centers, including measurements of ferritin (12/12, 100%), hemoglobin (11/12, 92%), transferrin saturation (TSAT) (6/12, 50.0%), and serum iron (5/12, 42%). About one-fifth of the patients had been treated with intravenous iron (218, 21.0%), whereas only a small percentage received oral iron (36, 3.5%). ID occurred in 97 patients (23.7% CI 95% 19.8-28.1). Patients with moderate/severe IBD activity (OR: 3.66; CI 95% 24.4-61.2; p = 0.007) or concomitant anemia (OR: 3.66; CI 95% 1.97-6.78; p < 0.001) had an increased likelihood of having ID. CONCLUSION: Patients with moderate/severe IBD activity or concomitant anemia are at increased risk of ID. Early detection and management of ID in patients with IBD is recommended.