Fabry disease: development and progression of left ventricular hypertrophy despite long-term enzyme replacement therapy.

BACKGROUND: Enzyme replacement therapy (ERT) may halt or attenuate disease progression in patients with Anderson-Fabry disease (AFD). However, whether left ventricular hypertrophy (LVH) can be prevented by early therapy or may still progress despite ERT over a long-term follow-up is still unclear. METHODS: Consecutive patients with AFD from the Independent Swiss-Fabry Cohort receiving ERT who were at least followed up for 5 years were included. Cardiac progression was defined as an increase of >10 g/m2 in left ventricular mass index (LVMI) between the first and the last available follow-up transthoracic echocardiography. RESULTS: 60 patients (35 (23-48) years, 39 (65%) men) were followed up for 10.5 (7.2-12.2) years. 22 had LVH at ERT start (LVMI of 150±38 g/m2). During follow-up, 22 (36%, 34±15 years) had LVMI progression of 12.1 (7-17.6) g/m2 per 100 patient-years, of these 7 (11%, 29±13 years) with no LVH at baseline. Three of them progressed to LVH. LVMI progression occurred mostly in men (17 of 39 (43%) vs 5 of 21 (24%), p<0.01) and after the age of 30 years (17 of 22 (77%)). LVH at ERT start was associated with LVMI progression (OR 1.3, 95% CI 1.1 to 2.6; p=0.02). A total of 19 (31%) patients experienced a major AFD-related event. They were predominantly men (17 of 19, 89%), older (45±11 vs 32±9 years) with baseline LVH (12 of 19, 63%), and 10 of 19 (52%) presented with LVMI progression. CONCLUSIONS: Over a median follow-up of >10 years under ERT, 36% of the patients still had LVMI cardiac progression, and 32%, predominantly older men, experienced major AFD-related events. LVH at treatment initiation was a strong predictor of LVMI progression and adverse events on ERT.

Anatomical and Electrophysiological Characteristics of Dual-Loop Re-Entry in Atypical Atrial Flutter: Implications for Mapping and Catheter Ablation.

Background: Atypical atrial flutter (AFL) can be challenging to ablate, especially when involving dual-loop re-entry. We sought to assess the electroanatomical characteristics of single- and dual-loop AFLs in patients undergoing catheter ablation. Methods: We analyzed 25 non-cavotricuspid isthmus-dependent macro-re-entrant AFL in 19 consecutive patients. Three-dimensional high-density activation mapping was performed, and active re-entry loops were confirmed by entrainment mapping. Results: Of 25 AFLs (24 left, 1 right atrial), 13 (52%) exhibited dual-loop re-entry. The most common circuits included, in 6/13 (46% of dual loops), a perimitral re-entry with a second loop around the right/left pulmonary veins (PV) and, in 6/13 (46%), involved a right PV ostium with a second loop around either a functional conduction block or another PV. Ablation at the common isthmus of dual-loop AFLs and at the critical isthmus of single-loop AFLs terminated the arrhythmia more frequently than ablation at a secondary isthmus of dual-loop AFLs (5/6 (83%) and 8/11 (73%) versus 1/8 (13%), respectively, p = 0.013). Conclusions: More than half of AFLs exhibited a dual-loop re-entrant mechanism. Most critical isthmuses were found at the mitral isthmus, the left atrial roof or right PV ostia. Ablation targeting the common isthmus resulted in a higher termination rate.

Anderson-Fabry disease management: role of the cardiologist.

Anderson-Fabry disease (AFD) is a lysosomal storage disorder characterized by glycolipid accumulation in cardiac cells, associated with a peculiar form of hypertrophic cardiomyopathy (HCM). Up to 1% of patients with a diagnosis of HCM indeed have AFD. With the availability of targeted therapies for sarcomeric HCM and its genocopies, a timely differential diagnosis is essential. Specifically, the therapeutic landscape for AFD is rapidly evolving and offers increasingly effective, disease-modifying treatment options. However, diagnosing AFD may be difficult, particularly in the non-classic phenotype with prominent or isolated cardiac involvement and no systemic red flags. For many AFD patients, the clinical journey from initial clinical manifestations to diagnosis and appropriate treatment remains challenging, due to late recognition or utter neglect. Consequently, late initiation of treatment results in an exacerbation of cardiac involvement, representing the main cause of morbidity and mortality, irrespective of gender. Optimal management of AFD patients requires a dedicated multidisciplinary team, in which the cardiologist plays a decisive role, ranging from the differential diagnosis to the prevention of complications and the evaluation of timing for disease-specific therapies. The present review aims to redefine the role of cardiologists across the main decision nodes in contemporary AFD clinical care and drug discovery.

[Atrial fibrillation: 2023 novelties for the general practitioner]. / Fibrillation auriculaire : nouveautés 2023 pour la médecine de premier recours.

Atrial fibrillation (AF) is the most frequent tachyarrhythmia with a significant morbimortality. The diagnosis is based on a 12 lead ECG. New technologies such as connected watches have shown similar sensibility and specificity. The new 4S scheme (Stroke risk, Symptoms, Severity of AF burden and Substrate) allows a global evaluation. Rhythm control mainly by catheter ablation is increasingly indicated. Management of cardiovascular risk factors is an essential part of the treatment of these patients.

La fibrillation auriculaire (FA) est la tachyarythmie la plus fréquente avec une morbimortalité conséquente. Le diagnostic se fait généralement par un ECG 12 pistes. Cependant, de nouvelles technologies, comme les montres connectées, ont montré d'excellents résultats avec une sensibilité et spécificité équivalentes. L'algorithme des 4S (risque d'AVC (stroke risk), sévérité des symptômes (symptoms), temporalité de la FA (severity of AF burden) et comorbidités (substrate)) permet une évaluation globale de la FA propre à chaque patient. L'indication à la stratégie de contrôle du rythme, principalement l'ablation par cathéter, devient plus fréquente. Le contrôle des facteurs de risque cardiovasculaire fait partie intégrante du traitement.

Safety, Efficacy and Prognostic Benefit of Atrial Fibrillation Ablation in Heart Failure with Preserved Ejection Fraction.

Up to 65% of patients with heart failure with preserved ejection fraction (HFpEF) develop AF during the course of the disease. This occurrence is associated with adverse outcomes, including pump failure death. Because AF and HFpEF are mutually reinforcing risk factors, sinus rhythm restoration may represent a disease-modifying intervention. While catheter ablation exhibits acceptable safety and efficacy profiles, no randomised trials have compared AF ablation with medical management in HFpEF. However, catheter ablation has been reported to result in lower natriuretic peptides, lower filling pressures, greater peak cardiac output and improved functional capacity in HFpEF. There is growing evidence that catheter ablation may reduce HFpEF severity, hospitalisation and mortality compared to medical management. Based on indirect evidence, early catheter ablation and minimally extensive atrial injury should be favoured. Hence, individualised ablation strategies stratified by stepwise substrate inducibility provide a logical basis for catheter-based rhythm control in this heterogenous population. Randomised trials are needed for definitive evidence-based guidelines.

A Lightweight and Interpretable Model to Classify Bundle Branch Blocks from ECG Signals.

Automatic classification of ECG signals has been a longtime research area with large progress having been made recently. However these advances have been achieved with increasingly complex models at the expense of model's interpretability. In this research, a new model based on multivariate autoregressive model (MAR) coefficients combined with a tree-based model to classify bundle branch blocks is proposed. The advantage of the presented approach is to build a lightweight model which combined with post-hoc interpretability can bring new insights into important cross-lead dependencies which are indicative of the diseases of interest.

Changes in LA volume and diameter correlate with mechanisms of recurrence after paroxysmal AF ablation.

Papathanasiou et al point out that the two different methods of LA volume and diameter measurement in our recent publication could limit the significance of the correlations we reported with PV reconnection and non-PV foci as mechanisms of post AF ablation recurrence. While we acknowledge the lack of statistically significant correlations of smaller echo derived LA diameter with PV reconnection or of a larger angiographic LA volume with non-PV foci, the congruent confidence intervals of this correlation suggest a statistical trend. Non-uniform LA dimensional changes as an expression of structural remodelling may also be a possible explanation. Published data indicates that angiographic LA volumes consistently exhibit a positive bias compared to echocardiographic volumes but do provide intra-procedural measurements better correlating with gold standard techniques like CT or MRI. Finally we agree with Papathanasiou et al that dynamic changes in LA dimensions likely correlate with early and late mechanisms of recurrence and merit prospective studies.

The significance of pulmonary veins isolation radiofrequency time and the evolution of left atrium volume on a twelve-year observational follow-up of paroxysmal atrial fibrillation patients.

AIMS: Pulmonary vein isolation (PVI) is the treatment of choice of paroxysmal atrial fibrillation (PAF). However, radiofrequency delivery at extra-PV sites may be additionally required. We compared clinical and procedural characteristics of patients undergoing PVI alone versus adjunctive extra-PV substrate modification, at first procedure and repeat procedures for AF recurrence. METHODS: 587 patients with PAF undergoing radiofrequency (RF) ablation were retrospectively included. Extra-PV ablation was performed in case of sustained AF despite PVI, or at re-do procedures without PV conduction recovery. Demographic, clinical and electrophysiological predictors of survival without re-intervention were analysed in patients' groups having undergone one (G1), two (G2) or three or more procedures (G3). RESULTS: At baseline procedure, PV RF ablation time was shorter in G1 compared to G2/G3 whereas extra-PV RF ablation time was greater in G3 compared to G1. The proportion of patients requiring PV re-isolation decreased with repeat procedures. Smaller LA before procedure 1 (p1) or p2 was associated with PV reconnection at p2. Conversely larger LA before p1 was associated with extra-PV substrate modification at p2. Late re-do procedure timing (>1yr) was associated with increasing LA volume. Only longer PV and total RF time predicted poorer survival free from AF without re-intervention. CONCLUSION: Longer PV RF time predicted requirement for re-ablation during follow-up. Smaller LA size predicted an increased probability of PV reconnection and decreased extra-PV substrate modification at p2. LA size decreased in patients undergoing early re-intervention, whereas it increased in patients undergoing re-intervention later on suggesting ongoing remodelling or progression.

Impact of SMART Pass filter in patients with ajmaline-induced Brugada syndrome and subcutaneous implantable cardioverter-defibrillator eligibility failure: results from a prospective multicentre study.

AIMS: Ajmaline challenge can unmask subcutaneous implantable cardioverter-defibrillator (S-ICD) screening failure in patients with Brugada syndrome (BrS) and non-diagnostic baseline electrocardiogram (ECG). The efficacy of the SMART Pass (SP) filter, a high-pass filter designed to reduce cardiac oversensing (while maintaining an appropriate sensing margin), has not yet been assessed in patients with BrS. The aim of this prospective multicentre study was to investigate the effect of the SP filter on dynamic Brugada ECG changes evoked by ajmaline and to assess its value in reducing S-ICD screening failure in patients with drug-induced Brugada ECGs. METHODS AND RESULTS: The S-ICD screening with conventional automated screening tool (AST) was performed during ajmaline challenge in subjects with suspected BrS. The S-ICD recordings were obtained before, during and after ajmaline administration and evaluated by the means of a simulation model that emulates the AST behaviour with and without SP filter. A patient was considered suitable for S-ICD if at least one sensing vector was acceptable in all tested postures. A sensing vector was considered acceptable in the presence of QRS amplitude >0.5 mV, QRS/T-wave ratio >3.5, and sense vector score >100. Of the 126 subjects (mean age: 42 ± 14 years, males: 61%, sensing vectors: 6786), 46 (36%) presented with an ajmaline-induced Brugada type 1 ECG. Up to 30% of subjects and 40% of vectors failed the screening during the appearance of Brugada type 1 ECG evoked by ajmaline. The S-ICD screening failure rate was not significantly reduced in patients with Brugada ECGs when SP filter was enabled (30% vs. 24%). Similarly, there was only a trend in reduction of vector-failure rate attributable to the SP filter (from 40% to 36%). The most frequent reason for screening failure was low QRS amplitude or low QRS/T-wave ratio. None of these patients was implanted with an S-ICD. CONCLUSION: Patients who pass the sensing screening during ajmaline can be considered good candidates for S-ICD implantation, while those who fail might be susceptible to sensing issues. Although there was a trend towards reduction of vector sensing failure rate when SP filter was enabled, the reduction in S-ICD screening failure in patients with Brugada ECGs did not reach statistical significance. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov Unique Identifier NCT04504591.

ECG-based score estimates the probability to detect Fabry Disease cardiac involvement.

OBJECTIVES: To elaborate an ECG-based nomogram estimating the probability to detect cardiac involvement by cardiac magnetic resonance (CMR) in Fabry Disease (FD). METHODS: 119 FD patients and 26 healthy controls underwent ECG and CMR. Test (n = 88, 60%) and validation cohorts (n = 57, 40%) were randomly derived. Cardiac involvement was defined as the presence of low myocardial T1 value, a CMR-surrogate of myocardial glycosphingolipid storage. ECG changes associated with low T1 value were identified in the test cohort, included in the nomogram and then tested in the validation cohort. RESULTS: Sokolow-Lyon index (AUC = 0.769), ratio between P-wave and PR-segment durations (Pwave/PRsegment) (AUC = 0.778), QRS duration (AUC = 0.703), QT (AUC = 0.769) duration were independently associated with the presence of low T1 on CMR at multivariate analysis. An ECG-based nomogram including these four parameters was accurate in identifying patients with CMR evidence of glycosphingolipid storage (c-index of the derived-nomogram = 0.90 in the test group; 0.81 in the validation group). CONCLUSION: We propose a practical ECG-based nomogram accurately estimating the probability to detect low T1 values by CMR in FD patients. The application of this tool in clinical practice could improve early detection of FD cardiac involvement.

Recognition of pre-hypertrophic cardiac involvement in Fabry Disease based on automated electrocardiographic measures.

BACKGROUND: Various electrocardiographic (ECG) indices have been shown to be useful for early recognition and staging of cardiac involvement in Fabry Disease (FD). However, many of them lack acceptable sensitivity and specificity. We assessed the value of automated ECG measures to discriminate between pre-hypertrophic FD and healthy individuals. METHODS AND RESULTS: Normal ECGs from 1496 healthy individuals (57.4% male, age 37.4 ± 13 years) were compared to those of 142 FD patients without LVH (37.3% male, age 41.5 ± 18 years). All ECGs were analyzed centrally and a total of 429 automated ECG measures per individual were included for step-wise analysis. The Cramer V statistic was first used to pick out those parameters which were helpful in discriminating between the two groups and a final selection was made by using two models, namely the FLD (Fisher Linear Discrimination) and the Logistic model, to optimise diagnostic performance for the detection of cardiac involvement in FD patients vs. specificity in healthy individuals. The three-step statistical analysis identified 9 ECG parameters as most significant for the discrimination between the groups. The combined discriminant score yielded 64% sensitivity and 97% specificity for correct classification of FD patients in the test sample with a logistic area under curve of the ROC analysis of 0.97. CONCLUSION: The combination of automated ECG measures identified via a stepwise statistical approach may be useful for detection of FD patients in the pre-hypertrophic stage. These data are promising for screening purposes in the very early stages of FD cardiomyopathy and warrant prospective confirmation.

Cardiac Involvement in Fabry Disease: JACC Review Topic of the Week.

Fabry disease (FD) is a rare X-linked inherited lysosomal storage disorder caused by deficient α-galactosidase A activity that leads to an accumulation of globotriasylceramide (Gb3) in affected tissues, including the heart. Cardiovascular involvement usually manifests as left ventricular hypertrophy, myocardial fibrosis, heart failure, and arrhythmias, which limit quality of life and represent the most common causes of death. Following the introduction of enzyme replacement therapy, early diagnosis and treatment have become essential to slow disease progression and prevent major cardiac complications. Recent advances in the understanding of FD pathophysiology suggest that in addition to Gb3 accumulation, other mechanisms contribute to the development of Fabry cardiomyopathy. Progress in imaging techniques have improved diagnosis and staging of FD-related cardiac disease, suggesting a central role for myocardial inflammation and setting the stage for further research. In addition, with the recent approval of oral chaperone therapy and new treatment developments, the FD-specific treatment landscape is rapidly evolving.

The myocardial phenotype of Fabry disease pre-hypertrophy and pre-detectable storage.

AIMS: Cardiac involvement in Fabry disease (FD) occurs prior to left ventricular hypertrophy (LVH) and is characterized by low myocardial native T1 with sphingolipid storage reflected by cardiovascular magnetic resonance (CMR) and electrocardiogram (ECG) changes. We hypothesize that a pre-storage myocardial phenotype might occur even earlier, prior to T1 lowering. METHODS AND RESULTS: FD patients and age-, sex-, and heart rate-matched healthy controls underwent same-day ECG with advanced analysis and multiparametric CMR [cines, global longitudinal strain (GLS), T1 and T2 mapping, stress perfusion (myocardial blood flow, MBF), and late gadolinium enhancement (LGE)]. One hundred and fourteen Fabry patients (46 ± 13 years, 61% female) and 76 controls (49 ± 15 years, 50% female) were included. In pre-LVH FD (n = 72, 63%), a low T1 (n = 32/72, 44%) was associated with a constellation of ECG and functional abnormalities compared to normal T1 FD patients and controls. However, pre-LVH FD with normal T1 (n = 40/72, 56%) also had abnormalities compared to controls: reduced GLS (-18 ± 2 vs. -20 ± 2%, P < 0.001), microvascular changes (lower MBF 2.5 ± 0.7 vs. 3.0 ± 0.8 mL/g/min, P = 0.028), subtle T2 elevation (50 ± 4 vs. 48 ± 2 ms, P = 0.027), and limited LGE (%LGE 0.3 ± 1.1 vs. 0%, P = 0.004). ECG abnormalities included shorter P-wave duration (88 ± 12 vs. 94 ± 15 ms, P = 0.010) and T-wave peak time (Tonset - Tpeak; 104 ± 28 vs. 115 ± 20 ms, P = 0.015), resulting in a more symmetric T wave with lower T-wave time ratio (Tonset - Tpeak)/(Tpeak - Tend) (1.5 ± 0.4 vs. 1.8 ± 0.4, P < 0.001) compared to controls. CONCLUSION: FD has a measurable myocardial phenotype pre-LVH and pre-detectable myocyte storage with microvascular dysfunction, subtly impaired GLS and altered atrial depolarization and ventricular repolarization intervals.

Impact of contact force sensing technology on outcome of catheter ablation of idiopathic pre-mature ventricular contractions originating from the outflow tracts.

AIMS: Catheter ablation of frequent idiopathic pre-mature ventricular contractions (PVC) is increasingly performed. While potential benefits of contact force (CF)-sensing technology for atrial fibrillation ablation have been assessed in several studies, the impact of CF-sensing on ventricular arrhythmia ablation remains unknown. This study aimed to compare outcomes of idiopathic outflow tract PVC ablation when using standard ablation catheters as opposed to CF-sensing catheters. METHODS AND RESULTS: In a retrospective multi-centre study, unselected patients undergoing catheter ablation of idiopathic outflow tract PVCs between 2013 and 2016 were enrolled. All procedures were performed using irrigated-tip ablation catheters and a 3D electro-anatomical mapping system. Sustained ablation success was defined as a ≥80% reduction of pre-procedural PVC burden determined by 24 h Holter ECG during follow-up. Overall, 218 patients were enrolled (median age 52 years, 51% males). Baseline and procedural data were similar in the standard ablation (24%) and the CF-sensing group (76%). Overall, the median PVC burden decreased from 21% (IQR 10-30%) before ablation to 0.2% (IQR 0-3.0%) after a median follow-up of 2.3 months (IQR 1.4-3.9 months). The rates of both acute (91% vs. 91%, P = 0.94) and sustained success (79% vs. 74%, P = 0.44) were similar in the standard ablation and the CF-sensing groups. No differences were observed in subgroups according to arrhythmia origin from the RVOT (65%) or LVOT (35%). Complications were rare (1.8%) and evenly distributed between the two groups. CONCLUSION: The use of CF-sensing technology is not associated with increased success rate nor decreased complication rate in idiopathic outflow tract PVC ablation.

Significance of post-pacing intervals shorter than tachycardia cycle length for successful catheter ablation of atypical flutter.

AIMS: During entrainment mapping of macro-reentrant tachycardias, the time difference (dPPI) between post-pacing interval (PPI) and tachycardia cycle length (TCL) is thought to be a function of the distance of the pacing site to the re-entry circuit and dPPI < 30 ms is considered within the re-entry circuit. This study assessed the importance of PPI < TCL as a successful target for atypical flutter ablation. METHODS AND RESULTS: A total of 177 ablation procedures were investigated. Surface electrocardiograms (ECGs) were evaluated and combined activation and entrainment mapping were performed to choose ablation sites. Each entrainment sequence immediately preceding static radiofrequency delivery at the same site was analysed. A total of 545 entrainment sequences were analysed. dPPI < 0 ms was observed in 45.3% (247/545) sequences. Ablation resulted in tachycardia termination more often at sites with dPPI < 0 (27.8% vs. 14.5%, P < 0.001) and with a progressively increasingly inverse correlation between dPPI duration and ablation success [odds ratio (OR): 0.974; 95% confidence interval (CI) 0.960-0.988; P < 0.001]. Tachycardia termination or cycle length prolongation also occurred more often at sites with dPPI < 0 (50.6% vs. 33.2%, P < 0.001) and with a similar inverse correlation with dPPI duration (OR: 0.972; 95% CI 0.960-0.984; P < 0.001). Twelve-lead synchronous isoelectric intervals were observed in 64.4% (163/253) flutter ECGs and were associated with a dPPI < 0 (75.3% vs. 55.8%, P < 0.001). CONCLUSION: When combined with activation mapping, a negative dPPI is a more effective parameter for identifying a target for successful ablation compared to a dPPI = 0-30 ms. Its occurrence is associated with a critical small narrow slow-conducting isthmus at the target site.

Right Atrial Complexity Evolves With Stepwise Left-Sided Persistent Atrial Fibrillation Substrate Ablation and Predicts Outcomes.

OBJECTIVES: This study sought to study the relation between outcomes of modified stepwise atrial fibrillation (AF) substrate ablation and dynamic electrogram characteristics in the coronary sinus (CS) and right atrium (RA). BACKGROUND: Identifying patients with persistent AF who will benefit from limited lesion sets versus those requiring extensive substrate modification is challenging. METHODS: We studied 70 patients undergoing persistent AF ablation, 43 with acute success (successful ablation [sABL], AF termination, or noninducibility) and 27 with failure (failed ablation [fABL], no termination, or induced AF of >5 minutes). Dominant frequency (DF) and sample entropy (SampEn, increasing with signal complexity) were measured on 30-second recordings of wide-coverage simultaneous RA and CS electrograms during baseline AF and induced AF post-pulmonary vein isolation and after left-sided electrogram-guided ablation steps (on the CS with or without the left atrium [LA]). RESULTS: At baseline AF, patients with sABL exhibited lower RA SampEn (p = 0.023) and lower CS DF (p = 0.030) compared to fABL. A positive RA-to-CS SampEn gradient predicted ablation failure (48% vs. 19% for patients in fABL vs. sABL; p = 0.015). A positive RA-to-CS DF gradient developed in patients with fABL after extra-pulmonary vein substrate modification, unlike patients with sABL (p = 0.0008). At 24 months, 76% of patients were AF free, and 68% were arrhythmia free. sABL was associated with fewer AF recurrences (hazard ratio: 0.31; 95% confidence interval: 0.12-0.84; p = 0.021). A negative RA-to-CS SampEn gradient at baseline was associated with freedom from AF (-0.14 ± 0.19 vs. 0.04 ± 0.18; p = 0.002). CONCLUSIONS: RA greater than CS electrogram complexity gradients at baseline or developing during ablation are associated with unfavorable acute and long-term outcomes of persistent AF ablation. These parameters allow monitoring of the effects of left-sided substrate ablation and, therefore, a rational choice of additional RA substrate modification.

[Isolated left ventricular hypertrophy : is it a Fabry disease?] / Hypertrophie ventriculaire gauche isolée : et si c'était une maladie de Fabry ?

Fabry disease, an X-linked disease, results from a deficiency of the lysosomal enzyme alpha-galactosidase A, which causes glycosphingolipids accumulation in the body. On the basis of the residual enzymatic activity level, a classical, severe multisystemic form and an attenuated cardiac variant form are distinguished. In all cases, patients can develop hypertrophic cardiomyopathy in adulthood, the severity of which is the leading cause of morbidity and mortality of the disease. The cardiomyopathy is usually isolated in the cardiac variant form, the most common form of the disease, and should be suspected in the presence of relatively specific ECG, echocardiographic and MRI characteristics.

La maladie de Fabry est liée au chromosome X et résulte d'un déficit de l'enzyme lysosomale alpha-galactosidase A, responsable de l'accumulation de glycosphingolipides dans l'organisme. On distingue une forme classique, multisystémique, sévère, et une forme atténuée ou variant cardiaque. Dans tous les cas, les adultes peuvent développer une cardiomyopathie hypertrophique (CMH), principale cause de morbi-mortalité de la maladie. Dans la forme variant cardiaque, la plus fréquente de la maladie, la CMH est généralement isolée. Elle peut être suspectée en présence de certaines anomalies ECG, échocardiographiques et/ou IRM, et amener à un dépistage.

[New onset atrial fibrillation in patients hospitalized with sepsis : is there an indication for anticoagulation ?] / Fibrillation auriculaire inaugurale lors d'un sepsis : y a-t-il une indication à une anticoagulation ?

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the general population and in patients with sepsis hospitalized in intensive care. The indication for long-term anticoagulation is based on expert recommendations that take into account data from the general population and thus recommend therapeutic anticoagulation for AF longer than 48 hours. However, a majority of new onset AF in intensive care seem to last less than 48 hours and additional risk factors such as the type of sepsis, the drugs administered as well as the presence of a central venous catheters, are involved. Moreover, the increased of minor and major hemorrhage renders it difficult to apply the usual recommendations. In this literature review, we will focus on the various risk factors, prognosis, and indication of long-term anticoagulation in the new onset AF in this population.

La fibrillation auriculaire (FA) est l'arythmie cardiaque la plus fréquente chez les patients en sepsis admis aux soins intensifs. L'indication à une anticoagulation au long cours se fonde sur des recommandations d'experts qui proposent une anticoagulation thérapeutique pour les FA de plus de 48 heures, compte tenu de données populationnelles. Or, la majorité de ces FA inaugurales semblent durer moins longtemps. La sévérité du sepsis, les médicaments administrés, la présence d'une voie veineuse centrale sont autant de facteurs de risque de survenue. S'y ajoute un risque hémorragique accru, rendant difficile l'application des recommandations usuelles. Nous allons, dans cette revue de littérature, nous intéresser aux facteurs de risque, au pronostic et à l'indication d'une anticoagulation au long cours de la FA inaugurale dans cette population.

An expert consensus document on the management of cardiovascular manifestations of Fabry disease.

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by pathogenic variants in the α-galactosidase A (GLA) gene that leads to reduced or undetectable α-galactosidase A enzyme activity and progressive accumulation of globotriaosylceramide and its deacylated form globotriaosylsphingosine in cells throughout the body. FD can be multisystemic with neurological, renal, cutaneous and cardiac involvement or be limited to the heart. Cardiac involvement is characterized by progressive cardiac hypertrophy, fibrosis, arrhythmias, heart failure and sudden cardiac death. The cardiac management of FD requires specific measures including enzyme replacement therapy or small pharmacological chaperones in patients carrying amenable pathogenic GLA gene variants and more general management of cardiac symptoms and complications. In this paper, we summarize current knowledge of FD-related heart disease and expert consensus recommendations for its management.

Emerging Concepts and Applied Machine Learning Research in Patients with Drug-Induced Repolarization Disorders.

The paper presents a review of current research to develop predictive models for automated detection of drug-induced repolarization disorders and shows a feasibility study for developing machine learning tools trained on massive multimodal datasets of narrative, textual and electrocardiographic records. The goal is to reduce drug-induced long QT and associated complications (Torsades-de-Pointes, sudden cardiac death), by identifying prescription patterns with pro-arrhythmic propensity using a validated electronic application for the detection of adverse drug events with data mining and natural language processing; and to compute individual-based predictive scores in order to further identify clinical conditions, concomitant diseases, or other variables that correlate with higher risk of pro-arrhythmic situations.