One year outcome and analysis of peri-device leak of left atrial appendage occlusion devices.

BACKGROUND: The prevalence of peri-device leak (PDL) of left atrial appendage occlusion (LAAO) devices has been previously reported. However, there have been only few data that compared different existing devices. The aim of this study was to assess the incidence of PDL with both devices WATCHMAN®, Boston Scientific and AMPLATZER Amulet®, Abbott Laboratories and to evaluate the clinical outcome at 12 months. METHODS: Consecutive patients who underwent LAAO between January 2018 and 2020 were randomly assigned to either WATCHMAN or AMPLATZER Amulet implantation based on a systematic 2-week alternation between both devices. LAA measurements were assessed using cardiac computed tomography angiography (CCTA) prior to and transesophageal echocardiography (TEE) during the procedure. At 8 weeks post-LAAO, patients underwent TEE and/or CCTA to identify the presence of PDL and/or device-related complications. Patients were then followed for 12 months to identify major adverse cardiovascular/embolic events. RESULTS: The cohort consisted of 51 patients (25 WATCHMAN, 26 AMPLATZER Amulet; mean age 76 ± 7 years; male gender 76%). Both groups were identically matched for demographics, comorbidities, and indication for LAAO. There were 19 patients who had PDL (13 WATCHMAN vs. 6 AMPLATZER Amulet, P-value = 0.033). Of them, 8 (15%) patients had significant PDL (7 WATCHMAN vs. 1 AMPLATZER Amulet, P-value = 0.018). On CCTA, the landing zone maximal diameter of the AMPLATZER Amulet device had the strongest correlation with the final deployed device size (Spearman's rho 0.92, P-value < 0.0001). In the multivariate analysis, male gender and device type were independent predictors of any PDL (P-values 0.016 and 0.031, respectively). On a mean follow-up of 12 months, the total number of events was more prevalent in the WATCHMAN group (P-value 0.008), but the incidence of cardio-embolic events reached borderline significance (16% vs. 0%, P-value = 0.051). CONCLUSIONS: Among patients who underwent LAAO, almost 15% had significant PDL with the majority belonging to the WATCHMAN group. Still, larger studies are warranted to evaluate its effectiveness in stroke prevention.

Contemporary Management of Severe Symptomatic Aortic Stenosis.

BACKGROUND: There were gaps between guidelines and practice when surgery was the only treatment for aortic stenosis (AS). OBJECTIVES: This study analyzed the decision to intervene in patients with severe AS in the EORP VHD (EURObservational Research Programme Valvular Heart Disease) II survey. METHODS: Among 2,152 patients with severe AS, 1,271 patients with high-gradient AS who were symptomatic fulfilled a Class I recommendation for intervention according to the 2012 European Society of Cardiology guidelines; the primary end point was the decision for intervention. RESULTS: A decision not to intervene was taken in 262 patients (20.6%). In multivariate analysis, the decision not to intervene was associated with older age (odds ratio [OR]: 1.34 per 10-year increase; 95% CI: 1.11 to 1.61; P = 0.002), New York Heart Association functional classes I and II versus III (OR: 1.63; 95% CI: 1.16 to 2.30; P = 0.005), higher age-adjusted Charlson comorbidity index (OR: 1.09 per 1-point increase; 95% CI: 1.01 to 1.17; P = 0.03), and a lower transaortic mean gradient (OR: 0.81 per 10-mm Hg decrease; 95% CI: 0.71 to 0.92; P < 0.001). During the study period, 346 patients (40.2%, median age 84 years, median EuroSCORE II [European System for Cardiac Operative Risk Evaluation II] 3.1%) underwent transcatheter intervention and 515 (59.8%, median age 69 years, median EuroSCORE II 1.5%) underwent surgery. A decision not to intervene versus intervention was associated with lower 6-month survival (87.4%; 95% CI: 82.0 to 91.3 vs 94.6%; 95% CI: 92.8 to 95.9; P < 0.001). CONCLUSIONS: A decision not to intervene was taken in 1 in 5 patients with severe symptomatic AS despite a Class I recommendation for intervention and the decision was particularly associated with older age and combined comorbidities. Transcatheter intervention was extensively used in octogenarians.

Xanthogranulomatous endometritis: A case report and literature review.

Xanthogranulomatous endometritis is a rare benign pathology mimicking endometrial carcinoma.

Analysis of weather exposure 7 days before occurrence of ST-segment elevation myocardial infarction.

BACKGROUND: Several studies have highlighted the relationship between weather patterns and the occurrence of ST-elevation myocardial infarction (STEMI). AIM: To evaluate the statistical association between the occurrence of STEMI and meteorological variables over the preceding 7 days. METHODS: This was a retrospective study, using prespecified data from the ORBI (Breton Regional Observatory on Myocardial Infarction) registry, which includes all consecutive patients hospitalized for STEMI in the geographical area of Brest, France. Over a 7-year period, we compared the number of STEMIs per week with the mean values of meteorological variables over the preceding 7 days. RESULTS: Overall, 7517 patients with STEMI were recorded in the ORBI registry between January 2009 and January 2016. After exclusion of patients not living in the geographical area of interest, 742 patients were included. The weekly incidence of STEMI ranged from 0 to 7 (median 2, interquartile range 1-3). In the univariate analysis, air temperature (odds ratio [OR] 1.05, 95% confidence interval [CI] 1.005-1.01 per 1°C decrease; P=0.03) and atmospheric pressure (OR 1.03, 95% CI 1.01-1.06 per 1 hPa increase; P=0.008) were associated with the weekly incidence of STEMI. In the multivariable analysis, air temperature (OR 1.06, 95% CI 1.01-1.10 per 1°C decrease; P=0.01), atmospheric pressure (OR 1.05, 95% CI 1.02-1.08 per 1 hPa increase; P<0.001) and duration of humidity>80% (OR 1.09, 95% CI 1.02-1.15 per 1hour increase; P=0.007) in the previous 7 days were associated with the occurrence of STEMI. CONCLUSIONS: In this specific geographical area, occurrence of STEMI was statistically associated with a decrease in air temperature, an increase in atmospheric pressure and an increase in humidity over the preceding 7-day period.

Patent Foramen Ovale and Ischemic Stroke in Patients With Pulmonary Embolism: A Prospective Cohort Study.

Background: Pulmonary embolism (PE) is associated with increased risk for ischemic stroke, but the underlying mechanism remains unclear. The authors hypothesized that paradoxical embolism through patent foramen ovale (PFO) should be the main mechanism. Objective: To determine the frequency of recent ischemic stroke in patients with symptomatic PE according to whether PFO was detected. Design: Prospective cohort study with masked assessment of stroke outcomes. (ClinicalTrials.gov: NCT01216423). Setting: 4 French hospital centers. Participants: 361 consecutive patients with symptomatic acute PE from 13 November 2009 through 21 December 2015. Intervention: Systematic contrast transthoracic echocardiography (TTE) and cerebral magnetic resonance imaging (MRI) within 7 days after enrollment. Measurements: Recent symptomatic or silent ischemic stroke was diagnosed on the basis of clinical examination and cerebral MRI showing a hypersignal on the trace diffusion-weighted image with reduction or pseudonormalization of apparent diffusion coefficient. Results: Contrast TTE was conclusive in 324 of 361 patients and showed PFO in 43 patients (13%). The median age was 66 years (interquartile range, 54 to 77 years). In total, 51% of patients (145/284) had associated deep venous thrombosis, 91% (279/306) had cardiovascular risk factors, and 10% (16/151) presented with arrhythmia (no difference between PFO and non-PFO groups). Cerebral MRI was conclusive in 315 patients. Recent ischemic stroke was more frequent in the PFO group than in the non-PFO group (9 of 42 patients [21.4%] vs. 15 of 273 patients [5.5%]; difference in proportions, 15.9 percentage points [95% CI, 4.7 to 30.7 percentage points]). Limitation: Because of inconclusive contrast TTE or MRI, 46 patients were excluded from analysis. Conclusion: Frequency of recent ischemic stroke in patients with symptomatic PE was higher in patients with PFO than in those without PFO. This finding supports the hypothesis that paradoxical embolism is an important mechanism of ischemic stroke in patients with PFO. Primary Funding Source: French Ministry of Health.

In vivo validation of Dosemap software use in interventional cardiology with dosimetrics indicators and peak skin dose evaluation.

OBJECTIVES: The aim of this study was to determine the accuracy of DoseMap™ software as compared to gafchromic film in real clinical practices. BACKGROUND: The radiation exposure from cardiovascular procedures could expose patients to potential risk of cancer and/or skin injury. New tools like Dosemap software were developed to estimate the patient skin dose in the cardiac catheterization laboratory. However, little data are available to validate this estimation of patient radiation skin dose. METHODS: This is a prospective cross-sectional study comparing the peak skin dose (PSD) measured by gafchromic film used as reference with an estimated PSD given by Dosemap software, in patients with BMI > 30 kg/m2 undergoing elective diagnostic and/or therapeutic interventional cardiology procedures, from April 2016 to December 2016, at the Brest University Hospital Centre, France. RESULTS: After four exclusions of patients for poor quality of gafchromic films, 90 patients were included, with 58 angiography (67.4%), 14 percutaneous interventions (16.3%), and 14 both (16.3%). The median PSDDosemap and PSDFilm were similar with 157 mGy [IQR: 99; 273] versus 158 mGy [IQR: 101; 295] (P = 0.65), respectively, with an excellent correlation (r = 0.95). The comparison between cumulative air kerma and PSDFilm was different 366 mGy [IQR: 246; 575] versus 158 mGy [IQR: 101; 295] (P < 0.01) with moderate correlation (r = 0.79). No correlation was found between the dose area product and PSDFilm (r = 0.51). CONCLUSION: DoseMap is an effective and valid method as compared to gafchromic films to estimate PSDs during interventional cardiologic procedures.

Head-to-head comparison of the diagnostic performance of coronary computed tomography angiography and dobutamine-stress echocardiography in the evaluation of acute chest pain with normal ECG findings and negative troponin tests: A prospective multicenter study.

OBJECTIVE: To perform a head-to-head comparison of coronary CT angiography (CCTA) and dobutamine-stress echocardiography (DSE) in patients presenting recent chest pain when troponin and ECG are negative. METHODS: Two hundred seventeen patients with recent chest pain, normal ECG findings, and negative troponin were prospectively included in this multicenter study and were scheduled for CCTA and DSE. Invasive coronary angiography (ICA), was performed in patients when either DSE or CCTA was considered positive or when both were non-contributive or in case of recurrent chest pain during 6month follow-up. The presence of coronary artery stenosis was defined as a luminal obstruction >50% diameter in any coronary segment at ICA. RESULTS: ICA was performed in 75 (34.6%) patients. Coronary artery stenosis was identified in 37 (17%) patients. For CCTA, the sensitivity was 96.9% (95% CI 83.4-99.9), specificity 48.3% (29.4-67.5), positive likelihood ratio 2.06 (95% CI 1.36-3.11), and negative likelihood ratio 0.07 (95% CI 0.01-0.52). The sensitivity of DSE was 51.6% (95% CI 33.1-69.9), specificity 46.7% (28.3-65.7), positive likelihood ratio 1.03 (95% CI 0.62-1.72), and negative likelihood ratio 1.10 (95% CI 0.63-1.93). The CCTA: DSE ratio of true-positive and false-positive rates was 1.70 (95% CI 1.65-1.75) and 1.00 (95% CI 0.91-1.09), respectively, when non-contributive CCTA and DSE were both considered positive. Only one missed acute coronary syndrome was observed at six months. CONCLUSIONS: CCTA has higher diagnostic performance than DSE in the evaluation of patients with recent chest pain, normal ECG findings, and negative troponine to exclude coronary artery disease.

Drug-Induced- or Rheumatic- Valvular Heart Disease in Patients Exposed to Benfluorex?

There is a risk of misdiagnosis between benfluorex-induced VHD and acute rheumatic fever (ARF)-related VHD due to common characteristics of both etiologies. We aimed at estimating the probability for a patient exposed to benfluorex presenting with VHD to have, at the same time, a history of ARF-related VHD. Such epidemiological approach could help at reducing the risk of misdiagnosis. We used INSEE data and related literature as well as various modeling hypotheses to drive and test a formula for calculating the probability of a patient presenting with VHD and a history of benfluorex intake to have a prior history of ARF-related VHD. Different scenarios were estimated by a Markov model on the life course of people born in France between 1940 and 1960. Sensitivity analyses were performed under these scenarios. According to the different scenarios and gender, the probability that a patient born between 1940 and 1960 presenting with VHD and a history of benfluorex intake would have had a prior history of ARF-related VHD varied from 0.2% to 2.7%. The probabilities by the year of birth were as follows: 0.8%-2.7% for a patient born in 1940, < 0.5% in all scenarios for patients born after 1955, and < 0.2% in all scenarios for patients, born in 1960. Our results indicate that the burden of ARF-related VHD is low in the patient population exposed to benfluorex. The probability of ARF related VHD should not be over-estimated in the diagnostic procedure of VHD.

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.

[Drug-induced valve heart disease]. / Valvulopathies médicamenteuses.

Drug-induced valve heart disease. Numerous reports have shown an unquestionable association between fibrotic valve heart disease (VHD) and the following drugs: ergot alkaloids (methysergide and ergotamine), ergot-derived dopaminergic agonists (pergolide and cabergoline) and drugs metabolized into norfenfluramine (fenfluramine, dexfenfluramine and benfluorex). These drugs have a common pharmacological action on a specific serotonin receptor - the 5HT2B receptor leading to VHD. All four valves can be affected, but the mitral and aortic valves are predominantly involved. Echocardiography is the method of choice to detect these VHD and evaluate its severity. The most characteristic feature is restriction of valve motion, mainly responsible for regurgitation. Histological examination is typical, but rarely available. Drug-induced VHD may be severe, requiring cardiac surgery. The subsequent course is not well documented, varies from one patient to another, with the possibility of regression, stabilisation or deterioration.

Valvulopathies médicamenteuses. Les valvulopathies médicamenteuses sont dues à un effet agoniste de certains médicaments sur les récepteurs cardiaques sérotoninergiques 5-HT2B. Les substances associées à leur survenue sont le méthysergide, l'ergotamine, la fenfluramine, la dexfenfluramine, le pergolide, la cabergoline, le benfluorex et l'ecstasy. Les valvulopathies médicamenteuses sont caractérisées par la présence d'une fibrose engainant les valves cardiaques. Elles sont à l'origine de fuites valvulaires essentiellement du coeur gauche, parfois associées à des sténoses valvulaires. Les atteintes polyvalvulaires sont fréquentes. L'échographie Doppler cardiaque est l'examen diagnostique clé car la clinique est peu sensible et peu spécifique. Les signes échographiques sont un épaississement valvulaire, une rétraction valvulaire et un mouvement valvulaire restrictif systolo-diastolique. Les formes frustes sont fréquentes. L'aspect anatomopathologique est caractéristique, mais rarement disponible. Les formes graves sont rares et peuvent nécessiter un remplacement valvulaire. L'évolution des valvulopathies médicamenteuses est mal connue, variable d'un patient à l'autre, avec possibilité de diminution, de stabilisation ou d'aggravation.

Calcifications in benfluorex-induced valve heart disease: a misknown association.

Benfluorex, an anorexigenic agent, is recognized to induce noncalcified restrictive valvular regurgitation. We report a well-documented case of a 73-year-old patient who developed heart failure with aortic and mitral regurgitation following benfluorex intake. Echocardiography and peroperative analysis found large mitral annular calcifications and aortic subvalvular calcifications. Pathology confirmed drug-induced valve heart disease (DIVHD). The presence of valvular apparatus calcification should not lead to diagnosis of degenerative valvular disease and a priori preclude the diagnosis of DIVHD.

Food and Drug Administration criteria for the diagnosis of drug-induced valvular heart disease in patients previously exposed to benfluorex: a prospective multicentre study.

AIMS: The Food and Drug Administration (FDA) criteria for diagnosis of drug-induced valvular heart disease (DIVHD) are only based on the observation of aortic regurgitation ≥ mild and/or mitral regurgitation ≥ moderate. We sought to evaluate the diagnostic value of FDA criteria in a cohort of control patients and in a cohort of patients exposed to a drug (benfluorex) known to induce VHD. METHODS AND RESULTS: This prospective, multicentre study included 376 diabetic control patients not exposed to valvulopathic drugs and 1000 subjects previously exposed to benfluorex. Diagnosis of mitral or aortic DIVHD was based on a combined functional and morphological echocardiographic analysis of cardiac valves. Patients were classified according to the FDA criteria [mitral or aortic-FDA(+) and mitral or aortic-FDA(-)]. Among the 376 control patients, 2 were wrongly classified as mitral-FDA(+) and 17 as aortic-FDA(+) (0.53 and 4.5% of false positives, respectively). Of those exposed to benfluorex, 48 of 58 with a diagnosis of mitral DIVHD (83%) were classified as mitral-FDA(-), and 901 of the 910 patients (99%) without a diagnosis of the mitral DIVHD group were classified as mitral-FDA(-). All 40 patients with a diagnosis of aortic DIVHD were classified as aortic-FDA(+), and 105 of the 910 patients without a diagnosis of aortic DIVHD (12%) were classified aortic-FDA(+). Older age and lower BMI were independent predictors of disagreement between FDA criteria and the diagnosis of DIVHD in patients exposed to benfluorex (both P ≤ 0.001). CONCLUSIONS: FDA criteria solely based on the Doppler detection of cardiac valve regurgitation underestimate for the mitral valve and overestimate for the aortic valve the frequency of DIVHD. Therefore, the diagnosis of DIVHD must be based on a combined echocardiographic and Doppler morphological and functional analysis of cardiac valves.

Frequency of drug-induced valvular heart disease in patients previously exposd to benfluorex: a multicentre prospective study.

AIMS: The epidemiologic link between benfluorex use and an increased global frequency of left heart valve regurgitation has been well documented. However, no data linking previous drug exposure to the frequency of diagnosis of drug-induced valvular heart disease (DI-VHD) are available. The present study was conducted to address this issue. METHODS AND RESULTS: This echocardiography reader-blinded, controlled study conducted in 10 centres between February 2010 and February 2012 prospectively included 835 subjects previously exposed to benfluorex referred by primary care physicians for echocardiography. Based on blinded off-line analysis, echocardiography findings were classified as: (i) DI-VHD⁺ for patients with an echocardiographic diagnosis of DI-VHD, (ii) inconclusive, and (iii) DI-VHD⁻ for patients without signs of DI-VHD. Fifty-seven (6.8%) patients exposed to benfluorex were classified as DI-VHD⁺, 733 (87.8%) patients were classified as DI-VHD⁻, and 45 (5.4%) were classified as inconclusive. Mitral and aortic DI-VHD were reported in 43 patients (5.1%) and 30 (3.6%) patients, respectively. Longer duration of exposure, female gender, smoking, and lower BMI were independently associated with a diagnosis of DI-VHD. Good inter-observer reproducibility was observed for the echocardiography classification (Kappa = 0.83, P < 0.00001). CONCLUSIONS: About 7% of patients without a history of heart valve disease previously exposed to benfluorex present echocardiography features of DI-VHD. Further studies are needed to study the natural history of DI-VHD and to identify risk factors for the development of drug-induced valve lesions.

Impact of selective serotonin reuptake inhibitor therapy on heart valves in patients exposed to benfluorex: a multicentre study.

BACKGROUND: Given the association between valvular heart disease and drugs that alter serotonin metabolism, concerns have been raised about the possibility of an association between selective serotonin reuptake inhibitor (SSRI) use and drug-induced valvular disease. In France, SSRI use has been suggested to be an important confounding factor in the development of heart valve lesions in patients exposed to benfluorex in the context of the 'Médiator scandal'. AIMS: To address the relationship between SSRI use and valve regurgitation and morphology in a large cohort of patients exposed to benfluorex. METHODS: Overall, 832 consecutive patients exposed to benfluorex prospectively referred to 10 centres underwent complete echocardiography examinations according to a standardized protocol. Echocardiograms were independently and blindly read off-line by two experts. RESULTS: Ninety patients had been exposed to SSRIs for 3 months or more. The proportions of patients with no or trivial, mild, moderate or severe mitral regurgitation (MR) or aortic regurgitation (AR) were not different between SSRI patients and non-SSRI patients (P=0.63 and 0.58, respectively). The frequencies of AR ≥ mild (20 [22.2%] vs 145 [19.5%]; P=0.55) and MR ≥ mild (14 [15.6%] vs 118 [15.9%]; P=0.93) were similar in SSRI patients and non-SSRI patients. The frequencies of aortic and mitral valve abnormalities suggestive of drug-induced toxicity were also similar in the two patient groups. Multivariable logistic regression analysis confirmed the absence of any identifiable relationship between AR or MR and morphological abnormalities and SSRI use in the present cohort. CONCLUSION: Exposure to SSRIs was not associated with an increased risk of heart valve regurgitation or morphological abnormalities suggestive of drug-induced toxicity in this large cohort of patients exposed to benfluorex.

Increased risk of left heart valve regurgitation associated with benfluorex use in patients with diabetes mellitus: a multicenter study.

BACKGROUND: Benfluorex was withdrawn from European markets in June 2010 after reports of an association with heart valve lesions. The link between benfluorex and valve regurgitations was based on small observational studies and retrospective estimations. We therefore designed an echocardiography-based multicenter study to compare the frequency of left heart valve regurgitations in diabetic patients exposed to benfluorex for at least 3 months and in diabetic control subjects never exposed to the drug. METHODS AND RESULTS: This reader-blinded, controlled study conducted in 10 centers in France between February 2010 and September 2011 prospectively included 376 diabetic subjects previously exposed to benfluorex who were referred by primary care physicians for echocardiography and 376 diabetic control subjects. Through the use of propensity scores, 293 patients and 293 control subjects were matched for age, sex, body mass index, smoking, dyslipidemia, hypertension, and coronary artery disease. The main outcome measure was the frequency of mild or greater left heart valve regurgitations. In the matched sample, the frequency and relative risk (odds ratio) of mild or greater left heart valve regurgitations were significantly increased in benfluorex patients compared with control subjects: 31.0% versus 12.9% (odds ratio, 3.55; 95% confidence interval, 2.03-6.21) for aortic and/or mitral regurgitation, 19.8% versus 4.7% (odds ratio, 5.29; 95% confidence interval, 2.46-11.4) for aortic regurgitation, and 19.4% versus 9.6% (odds ratio, 2.38; 95% confidence interval, 1.27-4.45) for mitral regurgitation. CONCLUSIONS: Our results indicate that the use of benfluorex is associated with a significant increase in the frequency of left heart valve regurgitations in diabetic patients. The natural history of benfluorex-induced valve abnormalities needs further research.