[Automated grouping of terms associated to cardiac valve fibrosis in MedDRA]. / Groupement automatisé de termes liés aux valvulopathies médicamenteuses dans MedDRA.

AIM: To propose an alternative approach for building custom groupings of terms that complements the usual approach based on both hierarchical method (selection of reference groupings in medical dictionary for regulatory activities [MedDRA]) and/or textual method (string search), for case reports extraction from a pharmacovigilance database in response to a safety problem. Here we take cardiac valve fibrosis as an example. METHODS: The list of terms obtained by an automated approach, based on querying ontology of adverse drug reactions (OntoADR), a knowledge base defining MedDRA terms through relationships with systematized nomenclature of medicine-clinical terms (SNOMED CT) concepts, was compared with the reference list consisting of 53 preferred terms obtained by hierarchical and textual method. Two queries were performed on OntoADR by using a dedicated software: OntoADR query tools. Both queries excluded congenital diseases, and included a procedure or an auscultation method performed on cardiac valve structures. Query 1 also considered MedDRA terms related to fibrosis, narrowing or calcification of heart valves, and query 2 MedDRA terms described according to one of these four SNOMED CT terms: "Insufficiency", "Valvular sclerosis", "Heart valve calcification" or "Heart valve stenosis". RESULTS: The reference grouping consisted of 53 MedDRA preferred terms. Our automated method achieved recall of 79% and precision of 100% for query 1 privileging morphological abnormalities, and recall of 100% and precision of 96% for query 2 privileging functional abnormalities. CONCLUSION: An alternative approach to MedDRA reference groupings for building custom groupings is feasible for cardiac valve fibrosis. OntoADR is still in development. Its application to other adverse reactions would require significant work for a knowledge engineer to define every MedDRA term, but such definitions could then be queried as many times as necessary by pharmacovigilance professionals.

An Infrequently Encountered Cause of Hemoptysis.

Mitral stenosis (MS) is not a common entity in modern-day medicine, especially in developed countries, as the most common etiology is still rheumatic fever. MS can present mainly with a wide range of cardiac symptoms. However, infrequently, MS can cause extra-cardiac symptoms as well. We present a case report of a patient with severe bioprosthetic mitral valve stenosis with intermittent hemoptysis and cardiogenic shock. We aim to report this case to remind clinicians about this uncommon but significant cause of hemoptysis. This case report also emphasizes the importance of utilizing a team approach while treating patients with severe MS, especially if they have serious complications that could be life-threatening. We also aim to add to the current literature by reporting this case.

Cardiac involvement in MPS patients: incidence and response to therapy in an Italian multicentre study.

BACKGROUND: Mucopolysaccharidoses (MPSs) are a group of lysosomal storage disorders caused by the deficit of lysosomal hydrolases involved in the degradation of glycosaminoglycans (GAGs). The course is chronic and progressive, with multisystemic involvement that often leads to cardiovascular disease. We describe the overall incidence and type of cardiac damage in a cohort of Italian MPS patients, and their progression over time, also with reference to treatment efficacy in patients under Enzyme Replacement Therapy (ERT). Moreover, we report a possible association between genetic variants and cardiac phenotype in homozygous and hemizygous patients to understand whether a more aggressive clinical phenotype would predict a greater cardiac damage. RESULTS: Our findings confirm that cardiac involvement is very common, already at diagnosis, in MPS VI (85.7% of our cohort), and in MPS II (68% of our cohort) followed by MPS I subjects (55% of our cohort). The most frequent heart defect observed in each MPS and at any time-point of evaluation was mitral insufficiency; 37% of our patients had mitral insufficiency already at diagnosis, and 60% at post-ERT follow-up. After at least six years of treatment, we observed in some cases (including 6 MPS II, 2 MPS IV and 2 MPS VI) a total regression or improvement of some signs of the cardiac pathology, including some valve defects, though excluding aortic insufficiency, the only valvulopathy for which no regression was found despite ERT. The general clinical phenotype proved not to be strictly correlated with the cardiac one, in fact in some cases patients with an attenuated phenotype developed more severe heart damage than patients with severe phenotype. CONCLUSIONS: In conclusion, our analysis confirms the wide presence of cardiopathies, at different extent, in the MPS population. Since cardiac pathology is the main cause of death in many MPS subtypes, it is necessary to raise awareness among cardiologists about early cardiac morpho-structural abnormalities. The encouraging data regarding the long-term effects of ERT, also on heart damage, underlines the importance of an early diagnosis and timely start of ERT.

Cardiac valvular surgery and history of anorectic drug intake: A retrospective study of a large population of benfluorex-exposed patients.

BACKGROUND: Anorectic drugs are overlooked as a cause of valvular heart disease (VHD). AIM: To describe the characteristics of a large population of patients with severe VHD who underwent cardiac surgery and had a history of benfluorex intake. METHODS: Retrospective observational and cross-sectional study of patients from a large French database (Office National d'Indemnisation des Accidents Médicaux). Clinical, echocardiographic, surgical and pathology findings were comprehensively collected from medical files. RESULTS: From a chart review of 9584 subjects, 1031 patients with VHD underwent cardiac surgery; 453 surgical patients were excluded because of VHD obviously unrelated to benfluorex exposure, six because of missing data and eight declined to participate. The final study population comprised 564 patients who had surgery between 1987 and 2019. Median age was 58 (interquartile range 50-65) years; 85% were female. Median duration of preoperative benfluorex exposure was 5.8 (3.3-10) years. Most patients had aortic and mitral valve disease. Pure or predominant aortic and/or mitral regurgitation were found in 84% of patients (n=471), and aortic or mitral stenosis (pure or combined with regurgitation) in 12% (n=67) and 15% (n=84), respectively. Overall, 403 aortic, 402 mitral and 64 tricuspid valve surgical procedures were collected. Aortic and mitral valves were found to be thickened, rigid and/or restrictive in most cases; restrictive tricuspid valve disease was seldom documented. Pathology was available in half of the population (276 patients); valvular fibrosis suggestive of drug-induced VHD was found in 222 patients, including 146 with expert examination. Mixed VHD aetiologies were discussed in 107 patients, including 54 with available pathology. CONCLUSIONS: Drug-induced VHD features are miscellaneous, including well-known restrictive valvular regurgitation, but also stenosis or combined regurgitation and stenosis. Besides a history of drug taking, thorough echocardiography and comprehensive surgical reports, pathology is key in the diagnostic procedure.

Medical decision making for 5D cardiac model: Template matching technique and simulation of the fifth dimension.

The purpose of this paper is to develop a 5D cardiac model which is inspired from the 5D model for the lungs. This model depends on five variables: the anatomical structure of the 3D heart, temporal dimension and the function of blood flow as the fifth dimension. To test this hypothesis, we took the same mathematical modeling as a reference for the fifth dimension of pulmonary flow where r→ρ(t)=r→v(t)+rf→(t) wherer→v(t) is the displacement vectors with approximate magnitudes by linear functions of the tidal volume and rf→(t) is the blood flow. The scans were acquired for 10 patients,in the 404 series for a total of 18,483 images studied in three cases: healthy patient, case of heart failure and aortic stenosis. Where r→vand r→f are the unit vectors along the volume of ejection and the blood flow axes, indicating the direction of motion of the object due to heart volume ejection and blood flow variations, respectively. The quantities of α and ß coefficients are determined from real-time patient image data. The alpha and beta coefficients are derived from the following dimension equations[mm / ml] [mm*ms / ml] . Since the cardiac system has two diastolic and systolic phases, we have calculated α1 and ß1 for telediatolic volume and α2 and ß2 for telesystolic volume throughout the cardiac cycle as a function of the location of the cuts chosen randomly. Fifth-dimensional experiments are used to track, simulate the behavior of blood flow to detect preliminary indications for the identification of stenosis or valve leakage. The average discrepancy was tabulated as the global fraction of systolic ejection. The results shown in Fig. 3 detect a correspondence between the hunting chamber cut and the flow sequence through the orifice of aorta for this patient with suspicious of having an aortic stenosis disease and an ejection fraction about 71% with a maximum of velocity (Vmax) detected=250 (cm / ms) = 2.5 (m / 10-3 s). In this case this patient has a minor stenosis in the aorta. It should be referred that the normalization of this measures is classified such as : Minor stenosis: area 1.5 cm2, Vmax <3 m / moderate stenosis: area 1.0 - 1.5 cm2, Vmax 3 - 4 m / severe stenosis: area <1.0 cm2, Vmax> 4 m / s. For a patient who has an aortic stenosis the cloud of the points is accumulated comparing to the origin of the axis while the patient with a symptom of insufficiency the points are widened with a remarkable gap in the trajectory. To solve the issue of the bad prediction, the inaccuracy of the clouds points of the model 5D, the lack of the exact measurements to estimate the degree of cardiac insufficiency (leakage or stenosis), a solution of 5D imagery was depicted. Our main contribution is to test the validity of the template-matching algorithm and the fifth dimension simulation to provide more clues to detect the aortic stenosis and cardiac insufficiency in the context of medical decision support.

Infective endocarditis in French Polynesia: Epidemiology, treatments and outcomes.

BACKGROUND: French Polynesia is a French overseas collectivity in the South Pacific Ocean, where data on infective endocarditis (IE) are lacking. AIMS: To investigate the epidemiology and outcomes of IE in French Polynesia. METHODS: All hospital records from consecutive patients hospitalized in Taaone Hospital, Tahiti, from 2015 to 2018, with an International Classification of Diseases, 10th revision, separation diagnosis of IE (I330), were reviewed retrospectively. RESULTS: From 190 hospital charts reviewed, 105 patients with a final diagnosis of IE, confirmed according to the modified Duke criteria, were included. The median duration of follow-up was 71 days (interquartile range 18-163 days). The mean age was 55±17 years, and there were 68 men (65%). Thirty-five patients (33%) had a history of rheumatic carditis and 43 (41%) had a prosthetic valve. There were 40 (38%) cases of staphylococcal IE, 32 (30%) of streptococcal IE and six (6%) of enterococcal IE. Cardiogenic shock, septic shock and clinically relevant cerebral complications were strongly associated with death from any cause (hazard ratio [HR] 16.85, 95% confidence interval [CI] 5.45-52.05 [P<0.001]; HR 2.62, 95% CI 1.23-5.56 [P=0.01]; and HR 4.14, 95% CI 1.92-8.92 [P<0.001], respectively). Seventy-three patients (69%) had a theoretical indication for surgery, which was performed in 38 patients (36%). Lack of surgery when there was a theoretical indication was significantly associated with death (HR 6.93, 95% CI 3.47-13.83; P<0.0001). CONCLUSIONS: The pattern of IE in French Polynesia differs from Western countries in many ways. Postrheumatic valvular disease remains the main underlying disease, and access to emergency heart surgery is still a challenge.

Targeting the 5-HT system: Potential side effects.

Targeting the serotonin (5-HT) system is no simple task: there are at least 15 5-HT receptors, in addition to a number of transporters and metabolizing enzymes. Multiple 5-HT receptor variants exist due to genetic variations and/or post translational modifications, splice variants or editing variants. Some receptors may form homo and heteromers. The 5-HT system is targeted by multiple drugs to treat a variety of diseases. Given the homology amongst the 5-HT and neighbouring receptor classes, only few drugs are actually selective for a single target. In fact, many 5-HT drugs act on a combination of targets, i.e. several receptors and/or transporters or enzymes. For instance, a number of antidepressants or antipsychotics act on 5-HT and other transmitter systems. Recently developed drugs may show target selectivity by design, based on the current state of knowledge, whereas many older compounds hit multiple targets since they were developed using phenotypic screens, as was done well into the 1980's. Ergot analogues, antipsychotics or antidepressants, fall into this category. As our knowledge developed over the last 25-30 years, some targets have very well-defined liabilities: for instance, 5HT2B or 5-HT2A receptor agonists, will produce valvulopathies or hallucinations, respectively, whereas 5-HT3 receptor antagonists, may lead to constipation. This short review will be limited in scope as there are multiple targets and even more compounds to discuss. This article is part of the special issue entitled 'Serotonin Research: Crossing Scales and Boundaries'.

[Assessment of intracardiac flows by Magnetic Resonance Imaging: The 4D Flow imaging]. / Évaluation des flux en imagerie par résonnance magnétique cardiaque : l'imagerie de flux 4D.

2D flow cardiac MRI is a well-established technique but has some current limitations in routine practice. New 4D flow MRI may overcome these limitations, providing dramatic dynamic imaging, easily understandable, allowing robust quantification of flows. 4D flow imaging should become soon the reference technic for valvular regurgitations and congenital heart disease.

Characteristics, aetiological spectrum and management of valvular heart disease in a Tunisian cardiovascular centre.

BACKGROUND: Valvular heart diseases occur frequently in Tunisia, but no precise statistics are available. AIM: To analyse the characteristics of patients with abnormal valvular structure and function, and to identify the aetiological spectrum, treatment and outcomes of valvular heart disease in a single cardiovascular centre in Tunisia. METHODS: This retrospective study included patients with abnormal valvular structure and function, who were screened by transthoracic echocardiography at a single cardiology department between January 2010 and December 2013. Data on baseline characteristics, potential aetiology, treatment strategies and discharge outcomes were collected from medical records. RESULTS: There were 959 patients with a significant valvular heart disease (mean age 53±17years; female/male ratio 0.57). Valvular heart disease was native in 77% of patients. Mitral stenosis was the most frequent lesion (44.1%), followed by multiple valve disease (22.3%). Rheumatic origin (66.6%) was the most frequent aetiology, followed by degenerative (17.2%) or ischaemic (8.1%) causes, endocarditis (1.4%) and congenital (0.9%) causes. Native valve disease was severe in 589 patients (61.4%). Percutaneous mitral balloon valvuloplasty was performed in 36.9% of patients with mitral stenosis. Among patients with severe valvular heart disease, surgical treatment was indicated for 446 (75.7%) patients. Only 161 (36.1%) patients were finally operated. Postoperative mortality was 13.6% for all valvular heart diseases. CONCLUSION: This retrospective study has shown that the main cause of valvular heart disease in Tunisia is rheumatic fever. Mitral stenosis and multiple valve disease are the most frequent valvular heart diseases in Tunisia. Percutaneous mitral balloon valvuloplasty and prosthetic valve replacement are the preferred treatment methods for valvular heart disease.

[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.

Tricuspid valve and percutaneous approach: No longer the forgotten valve!

Tricuspid valve disease is mainly represented by tricuspid regurgitation (TR), which is a predictor of poor outcome. TR is usually secondary, caused by right ventricle pressure or volume overload, the leading cause being left-sided heart valve diseases. Tricuspid surgery for severe TR is recommended during left valve surgery, and consists of either a valve replacement or, most often, a tricuspid repair with or without prosthetic annuloplasty. When TR persists or worsens after left valvular surgery, redo isolated tricuspid surgery is associated with high mortality. In addition, a sizeable proportion of patients present with tricuspid surgery deterioration over time, and need a reintervention, which is associated with high morbi-mortality rates. In this context, and given the recent major breakthrough in the percutaneous treatment of aortic and mitral valve diseases, the tricuspid valve appears an appealing challenge, although it raises specific issues. The first applications of transcatheter techniques for tricuspid valve disease were valve-in-valve and valve-in-ring implantation for degenerated bioprosthesis or ring annuloplasty. Some concerns remain regarding prosthesis sizing, rapid ventricular pacing and the best approach, but these procedures appear to be safe and effective. More recently, bicuspidization using a transcatheter approach for the treatment of native tricuspid valve has been published, in two patients. Finally, other devices are in preclinical development.

Occurrence, aetiology and challenges in the management of congestive heart failure in sub-Saharan Africa: experience of the Cardiac Centre in Shisong, Cameroon.

INTRODUCTION: The aim of the study was to investigate the occurrence, the aetiology and the management of congestive heart failure in the cardiac centre of the St. Elizabeth catholic general hospital Shisong in Cameroon. METHODS: Between November 2002 and November 2008, a population of 8121 patients was consulted in the referral cardiac centre of St. Elizabeth Catholic General Hospital. Of these patients, 462 were diagnosed with congestive heart failure according to the modified Framingham criteria for the diagnosis of heart failure. Complementary investigations used to confirm and establish the aetiology of the disease were the chest X-ray, electrocardiography, bi-dimensional Doppler echocardiography. RESULTS: The results showed that the occurrence of congestive heart failure in our centre was 5.7%. Congestive heart failure was diagnosed in 198 females and 264 males, aged between 8 and 86 years old (42.5±18 years old). Post rheumatic valvulopathies (14.6%) and congenital heart diseases (1.9%) were the first aetiologic factor of congestive heart failure in the young, meanwhile cardiomyopathies (8.3%) in elderly followed by hypertensive cardiomyopathy (4.4%). Congestive heart failure was also seen in adults with congenital heart diseases in 0.01%. In this zone of Cameroon, we discovered that HIV cardiomyopathy (1.6%) and Cor pulmonale (8%) were represented, aetiological factors not mentioned in previous studies conducted in urban areas of Cameroon. The mean duration of hospital stay for the compensation treatment was thirteen days, ranging between 7 and 21 days), the mortality being 9.2%. All the medications recommended for the treatment of congestive heart failure are available in our centre but many patients are not compliant to the therapy or cannot afford them. Financial limitation is causing the exacerbation of the disease and premature death. CONCLUSION: Our data show a high incidence of congestive heart failure mainly due to post rheumatic valvulopathies in young patients in our centre. National program to fight against rheumatic fever and complications are of great urgency in our country. The compensation treatment of congestive heart failure is challenging in our milieu, characterized by poor compliance and financial limitations.

Morbilidad en la clínica de enfermedad valvular cardíaca del Centro Cardiovascular Regional Ascardio: Barquisimeto-Venezuela / Morbidity in the clinic of valvular heart disease of the Regional Cardiovascular Center Ascardio: Barquisimeto-Venezuela

Se presentan los resultados de la revisión sistemática de 414 historias médicas de la Clínica de Enfermedad Valvular Cardíaca del Centro Cardiovascular Regional-Ascardio, en el período octubre 2002-julio 2008. Los casos fueron evaluados por el grupo de trabajo que integra la unidad. La enfermedad valvular cardíaca fue dividida según su presentación topográfica como lesión única o predominante, según su grado de severidad y repercusión hemodinámica. La válvula más frecuentemente comprometida fue la mitral (87,4%), seguida por la tricúspide (76,3%), aórtica (72,9%) y pulmonar (8,6%). 72,5% presenta al menos una lesión (insuficiencia o estenosis) severa. La etiología más frecuente fue la degenerativa (40,6 %). Según etiología, el promedio de edad es 41 años para la congénita, 47 años para la reumática y 64 años para la degenerativa. Se observa una importante limitación en el registro de factores de riesgo coronario, a pesar de ser un centro especializado. Se divide el análisis en patología valvular mitral única o predominante, aórtica predominante, doble lesión aórtica y mitral severas, patología valvular tricuspídea y pulmonar. Finalmente se presenta una discusión sobre la interpretación de los resultados.

It presents in this article the results of a sistematic review of 414 Medical History of the Clinic of Cardiovascular Heart Disease of the Cardiovascular Regional Center-Ascardio in the period October 2002-July 2008. The totality of the Clinic. The Valvular Heart Disease has been divided by its topography, as unique or predominant damage, grade of severity and hemodinamic repercusión. The heart valve more frecuently compromised was the mitral (87,4%), followed by the tricuspide (76,3%), aortic (72,9%) and pulmonar (8,6%). 72,5% presents at least one valvular damage (Regurgitation or stenosis) severe. The most frequent ethiology is Degenerative (40, 6%). According to the ethiology, the average age is 41 years for the congenital ethiology, 47 years for the reumathic and 64 years for the degenerative. It has been reported a limitation in the report of the coronary risk factors, despite is a specialized center. The analysis was divided in Mitral Valve Pathology unique or predominant, Aortic Valve Pathology unique or predominant, Doble severe damage of Mitral and Aortic Valves, Tricuspid and Pulmonar valve pathology. Finally it presents a discussion about the results.

Clínica de enfermedad valvular cardíaca del Centro Cardiovascular Regional-Ascardio: Barquisimeto-Estado Lara / Clinic of valvular heart disease of the Regional Cardiovascular Center-Ascardio: Barquisimeto-Lara State

La enfermedad valvular cardíaca es un importante problema de salud que requiere programas de atención especializada. Este artículo señala la justificación de una consulta de patologías valvulares y presenta la consulta organizada en el Centro Cardiovascular Regional Ascardio, su estructura, sus objetivos, protocolo de trabajo, requisito para el ingreso de pacientes y los vínculos que tiene con otras unidades y servicios. Se concluye que la consulta de enfermedad vascular cardíaca representa una experiencia positiva que puede servir de referencia para otros centros similares que tengan la iniciativa de organizar consultas especializadas.

Valvular heart disease poses a critical health problem requiring specialized medical care programs. This article highlights why a valvular heart disease clinic is justified and presents the clinic set up at Ascardio Regional Cardiovascular Center, as well as its structure, objectives, work protocol, requirements for patients´enrollment, and links with other units and services. In conclusion, the valvular heart disease clinic is a positive experience and a useful reference for other similar centers who may be taking the initiative in setting up specialized clinics.