Predictors and Risk Score for Immune Checkpoint-Inhibitor-Associated Myocarditis Severity.

Background: Immune-checkpoint inhibitors (ICI) are associated with life-threatening myocarditis but milder presentations are increasingly recognized. The same autoimmune process that causes ICI-myocarditis can manifest concurrent generalized myositis, myasthenia-like syndrome, and respiratory muscle failure. Prognostic factors for this "cardiomyotoxicity" are lacking. Methods: A multicenter registry collected data retrospectively from 17 countries between 2014-2023. A multivariable cox regression model (hazard-ratio(HR), [95%confidence-interval]) was used to determine risk factors for the primary composite outcome: severe arrhythmia, heart failure, respiratory muscle failure, and/or cardiomyotoxicity-related death. Covariates included demographics, comorbidities, cardio-muscular symptoms, diagnostics, and treatments. Time-dependent covariates were used and missing data were imputed. A point-based prognostic risk score was derived and externally validated. Results: In 748 patients (67% male, age 23-94), 30-days incidence of the primary composite outcome, cardiomyotoxic death, and overall death were 33%, 13%, and 17% respectively. By multivariable analysis, the primary composite outcome was associated with active thymoma (HR=3.60[1.93-6.72]), presence of cardio-muscular symptoms (HR=2.60 [1.58-4.28]), low QRS-voltage on presenting electrocardiogram (HR for ≤0.5mV versus >1mV=2.08[1.31-3.30]), left ventricular ejection fraction (LVEF) <50% (HR=1.78[1.22-2.60]), and incremental troponin elevation (HR=1.86 [1.44-2.39], 2.99[1.91-4.65], 4.80[2.54-9.08], for 20, 200 and 2000-fold above upper reference limit, respectively). A prognostic risk score developed using these parameters showed good performance; 30-days primary outcome incidence increased gradually from 3.9%(risk-score=0) to 81.3%(risk-score≥4). This risk-score was externally validated in two independent French and US cohorts. This risk score was used prospectively in the external French cohort to identify low risk patients who were managed with no immunosuppression resulting in no cardio-myotoxic events. Conclusions: ICI-myocarditis can manifest with high morbidity and mortality. Myocarditis severity is associated with magnitude of troponin, thymoma, low-QRS voltage, depressed LVEF, and cardio-muscular symptoms. A risk-score incorporating these features performed well. Trial registration number: NCT04294771 and NCT05454527.

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).

Genetics and pathophysiology of mitral valve prolapse.

Mitral valve prolapse (MVP) is a common condition affecting 2-3% of the general population, and the most complex form of valve pathology, with a complication rate up to 10-15% per year in advanced stages. Complications include mitral regurgitation which can lead to heart failure and atrial fibrillation, but also life-threatening ventricular arrhythmia and cardiovascular death. Sudden death has been recently brought to the forefront of MVP disease, increasing the complexity of management and suggesting that MVP condition is not properly understood. MVP can occur as part of syndromic conditions such as Marfan syndrome, but the most common form is non-syndromic, isolated or familial. Although a specific X-linked form of MVP was initially identified, autosomal dominant inheritance appears to be the primary mode of transmission. MVP can be stratified into myxomatous degeneration (Barlow), fibroelastic deficiency, and Filamin A-related MVP. While FED is still considered a degenerative disease associated with aging, myxomatous MVP and FlnA-MVP are recognized as familial pathologies. Deciphering genetic defects associated to MVP is still a work in progress; although FLNA, DCHS1, and DZIP1 have been identified as causative genes in myxomatous forms of MVP thanks to familial approaches, they explain only a small proportion of MVP. In addition, genome-wide association studies have revealed the important role of common variants in the development of MVP, in agreement with the high prevalence of this condition in the population. Furthermore, a potential genetic link between MVP and ventricular arrhythmia or a specific type of cardiomyopathy is considered. Animal models that allow to advance in the genetic and pathophysiological knowledge of MVP, and in particular those that can be easily manipulated to express a genetic defect identified in humans are detailed. Corroborated by genetic data and animal models, the main pathophysiological pathways of MVP are briefly addressed. Finally, genetic counseling is considered in the context of MVP.

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.

Prevalence, Characteristics, and Outcomes of COVID-19-Associated Acute Myocarditis.

BACKGROUND: Acute myocarditis (AM) is thought to be a rare cardiovascular complication of COVID-19, although minimal data are available beyond case reports. We aim to report the prevalence, baseline characteristics, in-hospital management, and outcomes for patients with COVID-19-associated AM on the basis of a retrospective cohort from 23 hospitals in the United States and Europe. METHODS: A total of 112 patients with suspected AM from 56 963 hospitalized patients with COVID-19 were evaluated between February 1, 2020, and April 30, 2021. Inclusion criteria were hospitalization for COVID-19 and a diagnosis of AM on the basis of endomyocardial biopsy or increased troponin level plus typical signs of AM on cardiac magnetic resonance imaging. We identified 97 patients with possible AM, and among them, 54 patients with definite/probable AM supported by endomyocardial biopsy in 17 (31.5%) patients or magnetic resonance imaging in 50 (92.6%). We analyzed patient characteristics, treatments, and outcomes among all COVID-19-associated AM. RESULTS: AM prevalence among hospitalized patients with COVID-19 was 2.4 per 1000 hospitalizations considering definite/probable and 4.1 per 1000 considering also possible AM. The median age of definite/probable cases was 38 years, and 38.9% were female. On admission, chest pain and dyspnea were the most frequent symptoms (55.5% and 53.7%, respectively). Thirty-one cases (57.4%) occurred in the absence of COVID-19-associated pneumonia. Twenty-one (38.9%) had a fulminant presentation requiring inotropic support or temporary mechanical circulatory support. The composite of in-hospital mortality or temporary mechanical circulatory support occurred in 20.4%. At 120 days, estimated mortality was 6.6%, 15.1% in patients with associated pneumonia versus 0% in patients without pneumonia (P=0.044). During hospitalization, left ventricular ejection fraction, assessed by echocardiography, improved from a median of 40% on admission to 55% at discharge (n=47; P<0.0001) similarly in patients with or without pneumonia. Corticosteroids were frequently administered (55.5%). CONCLUSIONS: AM occurrence is estimated between 2.4 and 4.1 out of 1000 patients hospitalized for COVID-19. The majority of AM occurs in the absence of pneumonia and is often complicated by hemodynamic instability. AM is a rare complication in patients hospitalized for COVID-19, with an outcome that differs on the basis of the presence of concomitant pneumonia.

The role of antibody responses against glycans in bioprosthetic heart valve calcification and deterioration.

Bioprosthetic heart valves (BHVs) are commonly used to replace severely diseased heart valves but their susceptibility to structural valve degeneration (SVD) limits their use in young patients. We hypothesized that antibodies against immunogenic glycans present on BHVs, particularly antibodies against the xenoantigens galactose-α1,3-galactose (αGal) and N-glycolylneuraminic acid (Neu5Gc), could mediate their deterioration through calcification. We established a large longitudinal prospective international cohort of patients (n = 1668, 34 ± 43 months of follow-up (0.1-182); 4,998 blood samples) to investigate the hemodynamics and immune responses associated with BHVs up to 15 years after aortic valve replacement. Early signs of SVD appeared in <5% of BHV recipients within 2 years. The levels of both anti-αGal and anti-Neu5Gc IgGs significantly increased one month after BHV implantation. The levels of these IgGs declined thereafter but anti-αGal IgG levels declined significantly faster in control patients compared to BHV recipients. Neu5Gc, anti-Neu5Gc IgG and complement deposition were found in calcified BHVs at much higher levels than in calcified native aortic valves. Moreover, in mice, anti-Neu5Gc antibodies were unable to promote calcium deposition on subcutaneously implanted BHV tissue engineered to lack αGal and Neu5Gc antigens. These results indicate that BHVs manufactured using donor tissues deficient in αGal and Neu5Gc could be less prone to immune-mediated deterioration and have improved durability.

Transthyretin Cardiac Amyloidosis Mimicking Immune Checkpoint-Induced Myocarditis in a Patient Treated with Atezolizumab and Bevacizumab for Advanced Hepatocellular Carcinoma: A Case Report.

Checkpoint kinase inhibitors are increasingly used in oncology. The combination of atezolizumab and bevacizumab is currently the recommended first-line treatment for advanced hepatocellular carcinoma. Cardiac toxicities of immunotherapies are rare, but can lead to discontinuation of treatment. Transthyretin cardiac amyloidosis is a rare condition, but its incidence is probably underestimated. Its symptoms may suggest immunotherapy-induced myocarditis. When immune-mediated myocarditis is suspected, a thorough cardiac evaluation is necessary to confirm or refute the diagnosis of myocarditis and to avoid unnecessary interruption of immunotherapy. Cardiac magnetic resonance imaging may raise suspicion of transthyretin cardiac amyloidosis, the diagnosis being confirmed by technetium pyrophosphate bone scintigraphy.

[Inflammatory cardiomyopathies: Diagnosis, correlations with imaging, interest of myocardial biopsy and place of molecular biology]. / Cardiomyopathies inflammatoires : diagnostic, corrélations avec l'imagerie, intérêt de la biopsie myocardique et place de la biologie moléculaire.

Inflammatory cardiomyopathies, also known as "myocarditis" are inflammatory pathologies affecting the myocardium and characterized by vast etiological and clinical heterogeneity. They can be asymptomatic, particularly in viral forms, or be responsible for sudden death, particularly in subjects under 35 years olds. Due to insufficient sensitivity and specificity of imaging and biology, the gold standard is histopathological and is performed on an endomyocardial biopsy or on explanted heart samples in a transplant context. Their classification has considerably evolved and is now based on the identification of a predominant cell pattern such as lymphocytic, neutrophilic or eosinophilic polynuclear, giant cell or granulomatous myocarditis. These different patterns will guide the etiological diagnosis, prognosis and the therapies to be implemented. Due to the importance of viral etiologies, this morphological analysis must be complemented by a virological analysis based on PCR with viral load quantification. In addition, some authors have been able to demonstrate the occurrence of myocarditis in patients with arrhythmogenic cardiomyopathy of genetic origin. The aim of this chapter is to review the current state of knowledge on inflammatory cardiomyopathies and their management.

Impact of Systematic Whole-body 18F-Fluorodeoxyglucose PET/CT on the Management of Patients Suspected of Infective Endocarditis: The Prospective Multicenter TEPvENDO Study.

BACKGROUND: Diagnostic and patients' management modifications induced by whole-body 18F-FDG-PET/CT had not been evaluated so far in prosthetic valve (PV) or native valve (NV) infective endocarditis (IE)-suspected patients. METHODS: In sum, 140 consecutive patients in 8 tertiary care hospitals underwent 18F-FDG-PET/CT. ESC-2015-modified Duke criteria and patients' management plan were established jointly by 2 experts before 18F-FDG-PET/CT. The same experts reestablished Duke classification and patients' management plan immediately after qualitative interpretation of 18F-FDG-PET/CT. A 6-month final Duke classification was established. RESULTS: Among the 70 PV and 70 NV patients, 34 and 46 were classified as definite IE before 18F-FDG-PET/CT. Abnormal perivalvular 18F-FDG uptake was recorded in 67.2% PV and 24.3% NV patients respectively (P < .001) and extracardiac uptake in 44.3% PV and 51.4% NV patients. IE classification was modified in 24.3% and 5.7% patients (P = .005) (net reclassification index 20% and 4.3%). Patients' managements were modified in 21.4% PV and 31.4% NV patients (P = .25). It was mainly due to perivalvular uptake in PV patients and to extra-cardiac uptake in NV patients and consisted in surgery plan modifications in 7 patients, antibiotic plan modifications in 22 patients and both in 5 patients. Altogether, 18F-FDG-PET/CT modified classification and/or care in 40% of the patients (95% confidence interval: 32-48), which was most likely to occur in those with a noncontributing echocardiography (P < .001) or IE classified as possible at baseline (P = .04), while there was no difference between NV and PV. CONCLUSIONS: Systematic 18F-FDG-PET/CT did significantly and appropriately impact diagnostic classification and/or IE management in PV and NV-IE suspected patients. CLINICAL TRIALS REGISTRATION: NCT02287792.

Impact of Mitral Regurgitation Severity and Left Ventricular Remodeling on Outcome After MitraClip Implantation: Results From the Mitra-FR Trial.

OBJECTIVES: This study aimed to identify a subset of patients based on echocardiographic parameters who might have benefited from transcatheter correction using the MitraClip system in the MITRA-FR (Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation) trial. BACKGROUND: It has been suggested that differences in the degree of mitral regurgitation (MR) and left ventricular (LV) remodeling may explain the conflicting results between the MITRA-FR and the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trials. METHODS: In a post hoc analysis, we evaluated the interaction between the intervention and subsets of patients defined based on MR severity (effective regurgitant orifice [ERO], regurgitant volume [RVOL] and regurgitant fraction [RF]), LV remodeling (end-diastolic and end-systolic diameters and volumes) and combination of these parameters with respect to the composite of death from any cause or unplanned hospitalization for heart failure at 24 months. RESULTS: We observed a neutral impact of the intervention in subsets with the highest MR degree (ERO ≥30 mm2, RVOL ≥45 ml or RF ≥50%) as in patients with milder MR degree. The same was seen in subsets with the milder LV remodeling using either diastolic or systolic diameters or volumes. When parameters of MR severity and LV remodeling were combined, there was still no benefit of the intervention including in the subset of patients with an ERO/end-diastolic volume ratio ≥ 0.15 despite similar ERO and LV end-diastolic volume compared with COAPT patients. CONCLUSIONS: In the MITRA-FR trial, we could not identify a subset of patients defined based on the degree of the regurgitation, LV remodeling or on their combination, including those deemed as having disproportionate MR, that might have benefited from transcatheter correction using the MitraClip system. (Multicentre Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation [MITRA-FR]; NCT01920698).

Hypermetabolism of the spleen or bone marrow is an additional albeit indirect sign of infective endocarditis at FDG-PET.

PURPOSE: This study aimed at determining the diagnostic implications of indirect signs of infection at FDG-PET-i.e., hypermetabolisms of the spleen and/or bone marrow (HSBM)-when documented in patients with known or suspected infective endocarditis (IE). METHODS: HSBM were defined by higher mean standardized uptake values comparatively to that of the liver on FDG-PET images from patients with a high likelihood of IE and prospectively included in a multicenter study. RESULTS: Among the 129 included patients, IE was ultimately deemed as definite in 88 cases. HSBM was a predictor of definite IE (P = 0.014; odds ratio (OR) 3.2), independently of the criterion of an abnormal cardiac FDG uptake (P = 0.0007; OR 9.68), and a definite IE was documented in 97% (29/30) of patients showing both HSBM and abnormal cardiac uptake, 78% (7/9) of patients with only abnormal cardiac uptake, 67% (42/63) of patients with only HSBM, and 37% (10/27) of patients with neither one. CONCLUSION: In this cohort with a high likelihood of IE, HSBM is an additional albeit indirect sign of IE, independently of the criterion of an abnormal cardiac uptake, and could reinforce the suspicion of IE in the absence of any other infectious, inflammatory, or malignant disease.

Overexpression of endothelial ß3 -adrenergic receptor induces diastolic dysfunction in rats.

AIMS: Diastolic dysfunction is common in cardiovascular diseases, particularly in the case of heart failure with preserved ejection fraction. The challenge is to develop adequate animal models to envision human therapies in the future. It has been hypothesized that this diastolic dysfunction is linked to alterations in the nitric oxide (• NO) pathway. To investigate this issue further, we investigated the cardiac functions of a transgenic rat model (Tgß3 ) that overexpresses the human ß3 -adrenoceptor (hß3 -AR) in the endothelium with the underlying rationale that the • NO pathway should be stimulated in the endothelium. METHODS AND RESULTS: Transgenic rats (Tgß3 ) that express hß3 -AR under the control of intercellular adhesion molecule 2 promoter were developed for a specific expression in endothelial cells. Transcriptomic analyses were performed on left ventricular tissue from 45-week-old rats. Among all altered genes, we focus on • NO synthase expression and endothelial function with arterial reactivity and evaluation of • NO and O2 •- production. Cardiac function was characterized by echocardiography, invasive haemodynamic studies, and working heart studies. Transcriptome analyses illustrate that several key genes are regulated by the hß3 -AR overexpression. Overexpression of hß3 -AR leads to a reduction of Nos3 mRNA expression (-72%; P < 0.05) associated with a decrease in protein expression (-19%; P < 0.05). Concentration-dependent vasodilation to isoproterenol was significantly reduced in Tgß3 aorta (-10%; P < 0.05), while • NO and O2 •- production was increased. In the same time, Tgß3 rats display progressively increasing diastolic dysfunction with age, as shown by an increase in the E/A filing ratio [1.15 ± 0.01 (wild type, WT) vs. 1.33 ± 0.04 (Tgß3 ); P < 0.05] and in left ventricular end-diastolic pressure [5.57 ± 1.23 mmHg (WT) vs. 11.68 ± 1.11 mmHg (Tgß3 ); P < 0.05]. In isolated working hearts, diastolic stress using increasing preload levels led to a 20% decrease in aortic flow [55.4 ± 1.9 mL/min (WT) vs. 45.8 ± 2.5 mL/min (Tgß3 ); P < 0.05]. CONCLUSIONS: The Tgß3 rat model displays the expected increase in • NO production upon ageing and develops diastolic dysfunction. These findings provide a further link between endothelial and cardiac dysfunction. This rat model should be valuable for future preclinical evaluation of candidate drugs aimed at correcting diastolic dysfunction.

Imaging of myocarditis and inflammatory cardiomyopathies.

Myocarditis encompasses a wide range of myocardial inflammatory diseases, including acute myocarditis, chronic myocarditis and inflammatory cardiomyopathies, and myocardial inflammation associated with other cardiomyopathies. Because of this heterogeneity in clinical presentation, and the infrequent use of endomyocardial biopsy, cardiac imaging has gradually acquired a key role in the non-invasive detection of myocardial inflammation, the assessment of aetiology and the management of specific therapies. This article summarizes the issue of myocarditis and myocardial inflammation in clinical practice, and reviews the role of different non-invasive imaging techniques in the exploration of myocardial inflammation.

The MITRA-HR study: design and rationale of a randomised study of MitraClip transcatheter mitral valve repair in patients with severe primary mitral regurgitation eligible for high-risk surgery.

AIMS: Percutaneous mitral valve repair has become an alternative to conventional surgery in patients suffering primary mitral regurgitation (MR) with a contraindication to surgery and could benefit patients at high surgical risk. The aim of the MITRA-HR study is to raise the level of evidence supporting the use of the MitraClip device in primary MR patients with a predefined high risk for surgery. METHODS AND RESULTS: MITRA-HR is a prospective, multicentre, randomised study designed to compare mitral valve repair using the MitraClip with conventional surgery in patients with severe primary mitral regurgitation at high risk for surgery. The surgical risk is defined by age, Society of Thoracic Surgeons (STS) risk estimate score, frailty, major organ system dysfunction, and procedure-specific impediments. The study will enrol 330 patients randomised between conventional surgery and MitraClip with a 1:1 ratio. The composite primary endpoint includes all-cause mortality, unplanned rehospitalisation for cardiovascular reasons, and mitral valve reintervention at 12 months. The main secondary safety endpoint is a major adverse event composite assessment evaluated 30 days after the procedure. CONCLUSIONS: The randomised MITRA-HR study is designed to provide additional supportive evidence of non-inferiority in efficacy and superiority in safety for percutaneous mitral valve repair using the MitraClip compared to conventional surgery in high surgical risk patients.

Drug-induced aortic valve stenosis: An under recognized entity.

BACKGROUND: We have been intrigued by the observation that aortic stenosis (AS) may be associated with characteristic features of mitral drug-induced valvular heart disease (DI-VHD) in patients exposed to valvulopathic drugs, thus suggesting that beyond restrictive heart valve regurgitation, valvulopathic drugs may be involved in the pathogenesis of AS. METHODS: Herein are reported echocardiographic features, and pathological findings encountered in a series of patients suffering from both AS (mean gradient >15mmHg) and mitral DI-VHD after valvulopathic drugs exposure. History of rheumatic fever, chest radiation therapy, systemic disease or bicuspid aortic valve disease were exclusion criteria. RESULTS: Twenty-five (19 females, mean age 62years) patients having both AS and typical features of mitral DI-VHD were identified. Mean transaortic pressure gradient was 32+/-13mmHg. Aortic regurgitation was ≥ mild in 24 (96%) but trivial in one. Known history of aortic valve regurgitation following drug initiation prior the development of AS was previously diagnosed in 17 patients (68%). Six patients underwent aortic valve replacement and 3 both aortic and mitral valve replacement. In the 9 patients with pathology analysis, aortic valvular endocardium was markedly thickened by dense non-inflammatory fibrosis, a characteristic feature of DI-VHD. CONCLUSION: The association between AS and typical mitral DI-VHD after valvulopathic drug exposure may not be fortuitous. Aortic regurgitation was usually associated to AS and preceded AS in most cases but may be lacking. Pathology demonstrated the potential role of valvulopathic drugs in the development of AS.

Left Ventricular Function Assessment Using 2 Different Cadmium-Zinc-Telluride Cameras Compared with a γ-Camera with Cardiofocal Collimators: Dynamic Cardiac Phantom Study and Clinical Validation.

UNLABELLED: This study compared two SPECT cameras with cadmium-zinc-telluride (CZT) detectors to a conventional Anger camera with cardiofocal collimators for the assessment of left ventricular (LV) function in a phantom and patients. METHODS: A gated dynamic cardiac phantom was used. Eighteen acquisitions were processed on each CZT camera and the conventional camera. The total number of counts within a myocardial volume of interest varied from 0.25 kcts to 1.5 Mcts. Ejection fraction was set to 33%, 45%, or 60%. Volume, LV ejection fraction (LVEF), regional wall thickening, and motion (17-segment model) were assessed. One hundred twenty patients with a low pretest likelihood of coronary artery disease and normal findings on stress perfusion SPECT were retrospectively analyzed to provide the reference limits for end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction, and regional function for each camera model. RESULTS: In the phantom study, for each ejection fraction value, volume was higher for the CZT cameras than for the conventional camera, resulting in a decreased but more accurate LVEF (all P < 0.001). In clinical data, body-surface-indexed EDV and ESV (mL/m(2)) were higher for one of the CZT cameras (Discovery NM 530c) than for the other (D-SPECT) or the conventional camera (respectively, 40.5 ± 9.2, 37 ± 7.9, and 35.8 ± 6.8 for EDV [P < 0.001] and 12.5 ± 5.3, 9.4 ± 4.2, and 8.3 ± 4.4 for ESV [P < 0.001]), resulting in a significantly decreased LVEF: 70.3% ± 9.1% vs. 75.2% ± 8.1% vs. 77.8% ± 9.3%, respectively (P < 0.001). CONCLUSION: The new CZT cameras yielded global LV function results different from those yielded by the conventional camera. LV volume was higher for the Discovery NM 530c than for the D-SPECT or the conventional camera, leading to decreased LVEF in healthy subjects. These differences should be considered in clinical practice and warrant the collection of a specific reference database.

Initial French experience of percutaneous mitral valve repair with the MitraClip: a multicentre national registry.

BACKGROUND: Percutaneous mitral valve repair (MVR) using the MitraClip(®) is a new option for severe mitral regurgitation (MR). AIM: To describe initial French experience regarding short-term and mid-term safety and efficacy. METHODS: A multicentre cohort reported experience of percutaneous MVR using the MitraClip(®) in French centres from December 2010 to September 2012. All patients were judged inoperable or at high surgical risk. Short-term and mid-term safety and efficacy results are presented. RESULTS: Sixty-two patients (72.7±11.4years; 71.7% men; 81.0% New York Heart Association [NYHA] class III or IV; logistic Euroscore 18.7±13.1%; 93.3% MR≥grade 3; 73.8% secondary MR) underwent percutaneous MVR using the MitraClip(®) under general anaesthesia. Procedural success was 95.2% (83.1% of patients received one clip; 16.9% received two clips). At discharge, 88.2% of implanted patients had a residual MR≤grade 2. Transthoracic echocardiography showed a significant decrease in ejection fraction (39.9±14.8% pre vs. 36.2±14.3% post), end-diastolic diameter (63.8±10.6mm vs. 61.4±12.3mm, respectively) and systolic pulmonary pressure (52.1±13.9mmHg vs. 44.7±10.9mmHg, respectively). The in-hospital mortality rate was 3.2%. The survival rate at 6-month follow-up was estimated at 83.1%, with 90.9% of patients in NYHA class I or II and residual MR≤grade 2 in 80% of cases. CONCLUSION: This initial French experience, despite being in its learning phase, showed promising results in patients considered ineligible for surgery, as observed in more experienced centres. Randomized studies are mandatory to confirm these preliminary data.