[Cardiac amyloidosis : simplifying the diagnosis of a complex disease]. / Amyloïdose cardiaque : simplifier le diagnostic d'une maladie complexe.

Amyloidosis is a systemic infiltrative disease characterized by deposition of misfolded proteins in tissues, notably affecting the heart. According to type of protein, various types are known with the most prevalent being light-chain and transthyretin amyloidosis. Prognosis is dismal with progression to severe heart failure without disease-modifying treatment. Latter having dramatically improved over the last decade, prompt diagnosis is of paramount importance. Recognition of early signs followed by multidisciplinary approach is essential for optimal patient management.

L'amyloïdose est une maladie infiltrative systémique caractérisée par le dépôt intratissulaire de protéines. Selon l'origine de la protéine on distingue différents types d'amyloïdose, mais ce sont essentiellement l'amyloïdose à chaînes légères et celle associée à la transthyrétine qui affectent le myocarde. Le pronostic de l'amyloïdose cardiaque est sombre, évoluant vers une insuffisance cardiaque terminale en absence de traitement spécifique. Avec l'arrivée récente de thérapies pouvant ralentir l'évolution de la maladie, un diagnostic précoce est devenu primordial. La reconnaissance des signes précurseurs de la maladie et la mise en place rapide de traitements dans un centre de référence de l'amyloïdose sont essentielles pour une gestion optimale des patients.

Prevention of esophageal lesions during atrial fibrillation catheter ablation using esophageal temperature monitoring: A systematic review and meta-analysis.

INTRODUCTION: The use of esophageal temperature monitoring (ETM) for the prevention of esophageal injury during atrial fibrillation (AF) ablation is often advocated. However, evidence supporting its use is scarce and controversial. We therefore aimed to review the evidence assessing the efficacy of ETM for the prevention of esophageal injury. METHODS: We performed a meta-analysis and systematic review of the available literature from inception to December 31, 2022. All studies comparing the use of ETM, versus no ETM, during radiofrequency (RF) AF ablation and which reported the incidence of endoscopically detected esophageal lesions (EDELs) were included. RESULTS: Eleven studies with a total of 1112 patients undergoing RF AF ablation were identified. Of those patients, 627 were assigned to ETM (56%). The overall incidence of EDELs was 9.8%. The use of ETM during AF ablation was associated with a non significant increase in the incidence of EDELs (12.3% with ETM, vs. 6.6 % without ETM, odds ratio, 1.44, 95%CI, 0.49, 4.22, p = .51, I2 = 72%). The use of ETM was associated with a significant increase in the energy delivered specifically on the posterior wall compared to patients without ETM (mean power difference: 5.13 Watts, 95% CI, 1.52, 8.74, p = .005). CONCLUSIONS: The use of ETM does not reduce the incidence of EDELs during RF AF ablation. The higher energy delivered on the posterior wall is likely attributable to a false sense of safety that may explain the lack of benefit of ETM. Further randomized controlled trials are needed to provide conclusive results.

Cytokine storm complicated by cardiogenic shock induced by anti-HER2 therapies.

Cytokine storm induced by anti-human epidermal growth factor receptor-2 (HER2) therapies has not been reported. We report a patient with breast cancer treated with trastuzumab/pertuzumab who developed severe biventricular dysfunction and cardiogenic shock (CS) 6 months after starting double anti-HER2 therapy. The CS was accompanied by severe systemic inflammation, and cardiac MRI (cMRI) showed structural changes typical of myocardial inflammation. The immuno-inflammatory profile showed significantly increased levels of activation of the complement system, proinflammatory cytokines (IL-1ß, IL-6, IL-18, IL-17A, TNF-alpha) with increased activity of classical monocytic, T helper 17 cells (Th17), CD4 T and effector memory CD8 T subsets, whereas NK cell activation was not observed. The data suggest an important role for monocytes as initiators of this FcγR-dependent antibody-dependent cytotoxicity, leading to the overactivation of an adaptive T cell response, in which Th17 cells may act in synergy with T helper 1 cells (Th1) to drive the severe cytokine release syndrome. After discontinuation of trastuzumab/pertuzumab, hypercytokinemia and complement activity normalized along with clinical recovery. Cardiac function returned to baseline within 2 months of initial presentation, together with a resolution of the myocardial inflammation on MRI.

Decongestion improving right heart function ameliorates prognosis after an acute heart failure episode.

BACKGROUND: The prognostic role of decongestion-related change of cardiac morphology and in particular right heart function has not been investigated comprehensively in AHF patients. METHODS AND RESULTS: This prospective observational single-centre study included consecutive patients hospitalized for treatment of AHF with reduced, mildly-reduced or preserved left ventricular ejection fraction (LVEF). Comprehensive transthoracic echocardiography at admission and discharge assessed decongestion-related change of cardiac function and morphology. The combined endpoint of 1 year all-cause mortality and cardiovascular rehospitalization explored the prognostic importance of decongestion-related change. The 176 study participants were 83 years old [74-87] and 54% were men. Fifty one (29%) had rLVEF, 65 (37%) mrLVEF, and 60 (34%) pLVEF. The proportion of de novo or worsening chronic HF was not different between LVEF groups. HF aetiology and cardiovascular risk factors were equally distributed across all groups except for a higher BMI in the pLVEF group. Decongestion equally reduced body weight, heart rate, systolic and diastolic blood pressure, tricuspid regurgitation gradient, and inferior vena cava diameter across all groups (P < 0.004 for all). Decongestion-related increase in TAPSE independent of the LVEF was associated with improvement of right-ventricular-pulmonary artery coupling and a lower incidence of the combined outcome in the Cox proportional hazard risk analysis (unadjusted HR 0.50 95% CI 0.33-0.78, P = 0.002; adjusted HR 0.46 95% CI: 0.33-0.78, P = 0.001). CONCLUSIONS: Decongestion-related increase in TAPSE and recovery of RV/pulmonary artery coupling was observed across all LVEF groups and associated with a risk reduction for the combined endpoint highlighting the important prognostic role of right heart recovery after an AHF episode.

Feasibility of adenosine stress cardiovascular magnetic resonance perfusion imaging in patients with MR-conditional transvenous permanent pacemakers and defibrillators.

BACKGROUND: The use of stress perfusion-cardiovascular magnetic resonance (CMR) imaging remains limited in patients with implantable devices. The primary goal of the study was to assess the safety, image quality, and the diagnostic value of stress perfusion-CMR in patients with MR-conditional transvenous permanent pacemakers (PPM) or implantable cardioverter-defibrillators (ICD). METHODS: Consecutive patients with a transvenous PPM or ICD referred for adenosine stress-CMR were enrolled in this single-center longitudinal study. The CMR protocol was performed using a 1.5 T system according to current guidelines while all devices were put in MR-mode. Quality of cine, late-gadolinium-enhancement (LGE), and stress perfusion sequences were assessed. An ischemia burden of ≥ 1.5 segments was considered significant. We assessed the safety, image quality and the occurrence of interference of the magnetic field with the implantable device. In case of ischemia, we also assessed the correlation with the presence of significant coronary lesions on coronary angiography. RESULTS: Among 3743 perfusion-CMR examinations, 66 patients had implantable devices (1.7%). Image quality proved diagnostic in 98% of cases. No device damage or malfunction was reported immediately and at 1 year. Fifty patients were continuously paced during CMR. Heart rate and systolic blood pressure remained unchanged during adenosine stress, while diastolic blood pressure decreased (p = 0.007). Six patients (9%) had an ischemia-positive stress CMR and significant coronary stenoses were confirmed by coronary angiography in all cases. CONCLUSION: Stress perfusion-CMR is safe, allows reliable ischemia detection, and provides good diagnostic value.

Myocardial extracellular volume by T1 mapping: a new marker of arrhythmia in mitral valve prolapse.

OBJECTIVES: We aimed to evaluate the relationship between mitral annular disjunction (MAD) severity and myocardial interstitial fibrosis at the left ventricular (LV) base in patients with mitral valve prolapse (MVP), and to assess the association between severity of interstitial fibrosis and the occurrence of ventricular arrhythmic events. BACKGROUND: In MVP, MAD has been associated with myocardial replacement fibrosis and arrhythmia, but the importance of interstitial fibrosis remains unknown. METHODS: In this retrospective study, 30 patients with MVP and MAD (MVP-MAD) underwent cardiovascular magnetic resonance (CMR) with assessment of MAD length, late gadolinium enhancement (LGE), and basal segments myocardial extracellular volume (ECVsyn). The control group included 14 patients with mitral regurgitation (MR) but no MAD (MR-NoMAD) and 10 patients with normal CMR (NoMR-NoMAD). Fifteen MVP-MAD patients underwent 24 h-Holter monitoring. RESULTS: LGE was observed in 47% of MVP-MAD patients and was absent in all controls. ECVsyn was higher in MVP-MAD (30 ± 3% vs 24 ± 3% MR-NoMAD, p < 0.001 and vs 24 ± 2% NoMR-NoMAD, p < 0.001), even in MVP-MAD patients without LGE (29 ± 3% vs 24 ± 3%, p < 0.001 and vs 24 ± 2%, p < 0.001, respectively). MAD length correlated with ECVsyn (rho = 0.61, p < 0.001), but not with LGE extent. Four patients had history of out-of-hospital cardiac arrest; LGE and ECVsyn were equally performant to identify those high-risk patients, area under the receiver operating characteristic (ROC) curve 0.81 vs 0.83, p = 0.84). Among patients with Holter, 87% had complex ventricular arrhythmia. ECVsyn was above the cut-off value in all while only 53% had LGE. CONCLUSION: Increase in ECVsyn, a marker of interstitial fibrosis, occurs in MVP-MAD even in the absence of LGE, and was correlated with MAD length and increased risk of out-of-hospital cardiac arrest. ECV should be includedin the CMR examination of MVP patients in an effort to better assess fibrous remodelling as it may provide additional value beyond the assessment of LGE in the arrhythmic risk stratification.

[Cardiotoxicity of immune checkpoint inhibitors used in cancer treatment]. / Cardiotoxicité des inhibiteurs de points de contrôle immunitaire utilisés dans le traitement des cancers.

Immune checkpoint inhibitors (ICI) have revolutionized the field of oncology, by reshaping the prognosis of many cancers and are progressively becoming the standard of care. One of the costs of these advances is the emergence of a new spectrum of immune-related adverse events (irAEs), of which cardiovascular irAEs are particularly feared. ICI-induced myocarditis is often a diagnostic challenge because of the vast heterogeneity of clinical presentations, and it is associated with a high mortality rate of around 50%. The present article summarizes the cardiac manifestations, the diagnostic strategy and the therapeutic management of patients with ICI-induced myocarditis used in the treatment of cancer.

Les inhibiteurs de points de contrôle immunitaire (ICI), ou immune checkpoint inhibitors (ICI), ont révolutionné la prise en charge de nombreux cancers en améliorant significativement la survie des patients et en devenant progressivement la norme de soins. Cette efficacité a néanmoins pour prix un taux élevé d'effets indésirables immunomédiés avec un large spectre d'organes touchés. Les toxicités cardiaques, dominées par la myocardite induite par les ICI, sont particulièrement redoutées du fait des difficultés diagnostiques et du risque d'évolution rapidement défavorable associée à une mortalité élevée, de l'ordre de 50 %. Le présent article s'intéresse aux manifestations cardiaques, à la stratégie diagnostique ainsi qu'à la prise en charge des patients présentant une myocardite induite par les ICI utilisés dans le traitement du cancer.

[Cardiac amyloidosis†: a rare disease†?] / Amyloïdose cardiaque: une maladie rare†?

Cardiac amyloidosis is an infiltrative cardiomyopathy, typically conducting to heart failure with preserved ejection fraction. There are several causes for the disease, from which two can already be seen in the young patient and are due to either genetic mutation or neoplasia. A third, non genetic cause, typically affects older patients (previously called senile amyloidosis) and appears to be much more prevalent than initially reported. A careful initial work-up and a high index of suspicion are important to detect as early as possible the disease, as it is associated with a poor prognosis in the late stage. A standardized diagnostic approach has been proposed with the use of bone scintigraphy, recently recognized as a sensitive diagnostic tool for this type of amyloidosis. With new disease modifying therapies recently becoming available, a more active diagnostic strategy is justified.

L'amyloïdose cardiaque est une cardiomyopathie infiltrative qui mène typiquement à une insuffisance cardiaque à fraction d'éjection préservée. Il existe différentes causes à cette maladie, avec des formes génétiques ou néoplasiques qui peuvent toucher le sujet jeune. Une troisième forme d'amyloïdose cardiaque, non génétique, touche essentiellement le sujet âgé (anciennement appelée amyloïdose sénile) et s'avère nettement plus prévalente qu'initialement suspectée. Un bilan initial systématique par imagerie et un haut index de suspicion sont indispensables pour détecter le plus précocement possible cette maladie au pronostic réservé. L'apport récent de la scintigraphie au DPD (dicarboxypropane disphosphonate) a été essentiel à cet égard. L'arrivée sur le marché de nouveaux médicaments pouvant ralentir la progression de la maladie justifie la mise en place d'une stratégie diagnostique plus active.

Impact of total ischemic time on manual thrombus aspiration benefit during primary percutaneous coronary intervention.

BACKGROUND: The benefits of manual thrombus aspiration (TA) during primary percutaneous coronary intervention (pPCI) for ST-elevation myocardial infarction (STEMI) remain uncertain. We assessed the influence of total ischemic time (TIT) on clinical outcomes among STEMI patients undergoing manual TA during pPCI. METHODS AND RESULTS: We conducted a retrospective study of patients enrolled in the Acute Myocardial Infarction in Switzerland Plus registry. STEMI patients undergoing pPCI with (TA group) or without (PCI-alone group) manual TA were stratified based on short (<3 hours), intermediate (3-6 hours), and long (>6 hours) TIT. The primary endpoint was in-hospital all-cause mortality. The secondary endpoint was in-hospital major adverse cardiac events (MACE), a composite of all-cause death, myocardial reinfarction and stroke. Between 2008 and 2014, 4'154 patients (TA 48%) were included. Risk-adjusted in-hospital all-cause mortality was not different between TA and PCI-alone groups (OR 1.29; 95%CI 0.83-1.98; p=0.26), whereas there was significantly increased risk of MACE (OR 1.52; 95%CI 1.05-2.19; p=0.03) in patients treated with manual TA compared with PCI-alone. There was no significant difference between manual TA and PCI-alone with respect to risk-adjusted all-cause mortality according to TIT groups, but risk-adjusted MACE rates were significantly higher in the group of patients with long TIT treated with manual TA compared with PCI-alone (OR 2.42; 95%CI 1.16-5.04; p=0.02). CONCLUSION: In a large registry of STEMI patients, manual TA was not associated with lower risk-adjusted in-hospital all-cause mortality compared with PCI-alone regardless of TIT but was associated with significantly greater risk of MACE. In patients with prolonged TIT, manual TA was associated with higher risk-adjusted MACE rates compared with PCI-alone.

Stress Perfusion CMR in Patients With Known and Suspected CAD: Prognostic Value and Optimal Ischemic Threshold for Revascularization.

OBJECTIVES: This study sought to determine the ischemia threshold and additional prognostic factors that identify patients for safe deferral from revascularizations in a large cohort of all-comer patients with known or suspected coronary artery disease (CAD). BACKGROUND: Stress-perfusion cardiac magnetic resonance (CMR) is increasingly used in daily practice for ischemia detection. However, there is insufficient evidence about the ischemia burden that identifies patients who benefit from revascularization versus those with a good prognosis who receive drugs only. METHODS: All patients with known or suspected CAD referred to stress-perfusion CMR for myocardial ischemia assessment were prospectively enrolled. The CMR examination included standard functional adenosine stress first-pass perfusion (gadobutrol 0.1 mmol/kg Gadovist, Bayer AG, Zurich, Switzerland) and late gadolinium enhancement (LGE) acquisitions. Presence of ischemia and ischemia burden (number of ischemic segments on a 16-segment model), and of scar and scar burden (number and transmurality of scar segments in a 17-segment model) were assessed. The primary endpoint was a composite of cardiac death, nonfatal myocardial infarction (MI), and late coronary revascularization (>90 days post-CMR); the secondary endpoint was a composite of cardiac death and nonfatal MI. RESULTS: During a follow-up of 2.5 ± 1.0 years, 86 and 32 of 1,024 patients (1,103 screened patients) experienced the primary and secondary endpoints, respectively. On Kaplan-Meier curves for the primary and secondary endpoints, patients without ischemia had excellent outcomes that did not differ from patients with <1.5 ischemic segments. In multivariate Cox regression analyses of the entire population and of the subgroups, ischemia burden (threshold: ≥1.5 ischemic segments) was consistently the strongest predictor of the primary and secondary endpoints with hazard ratios (HRs) of 7.42 to 8.72 (p < 0.001), whereas age (≥67 years), left ventricular ejection fraction (≤40%), and scar burden (LGE score ≥0.03) contributed significantly, but to a lesser extent, in all models with HRs of 2.01 to 3.48, 1.75 to 1.96, and 1.66 to 1.76, respectively. CONCLUSIONS: In a large all-comer patient cohort with known and suspected CAD, an ischemia burden of ≥1.5 ischemic segments on stress-perfusion CMR was the strongest predictor of the primary and secondary endpoints. Patients with zero or 1 ischemic segment can be safely deferred from revascularizations.