Parenteral anticoagulants in heart disease: Current status and perspectives (Section II). Position Paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease.

Anticoagulants are a mainstay of cardiovascular therapy, and parenteral anticoagulants have widespread use in cardiology, especially in acute situations. Parenteral anticoagulants include unfractionated heparin, low-molecular-weight heparins, the synthetic pentasaccharides fondaparinux, idraparinux and idrabiotaparinux, and parenteral direct thrombin inhibitors. The several shortcomings of unfractionated heparin and of low-molecular-weight heparins have prompted the development of the other newer agents. Here we review the mechanisms of action, pharmacological properties and side effects of parenteral anticoagulants used in the management of coronary heart disease treated with or without percutaneous coronary interventions, cardioversion for atrial fibrillation, and prosthetic heart valves and valve repair. Using an evidence-based approach, we describe the results of completed clinical trials, highlight ongoing research with currently available agents, and recommend therapeutic options for specific heart diseases.

Implantation de valve aortique par voie transcatheter (TAVI): update sur les indications [Transcatheter aortic valve implantation (TAVI): update on the indications].

Although surgical aortic valve replacement has been the standard of care for patient with severe aortic stenosis, transcatheter aortic valve implantation (TAVI) is now a fair standard of care for patients not eligible or high risk for surgical treatment. The decision of therapeutic choice between TAVI and surgery considers surgical risk (estimated by the Euro-SCORE and STS-PROM) as well as many parameters that go beyond the assessment of the valvular disease's severity by echocardiography: a multidisciplinary assessment in "Heart Team" is needed to assess each case in all its complexity.

Sélection in vivo par phage display dans un modèle de sténose valvulaire aortique chez la souris pour la découverte de nouveaux peptides ciblant la valve aortique

La sténose valvulaire aortique (SVA) est la maladie des valves cardiaques la plus répandue dans les pays développés qui touche les personnes âgées. La SVA est un processus actif caractérisé par des dépôts de lipides, de l’inflammation, de la fibrose et une calcification active des feuillets qui progresse vers un épaississement et durcissement de la valve aortique et une diminution de l’aire de la valve aortique. Nous avons émis l’hypothèse que la pathogénèse de la SVA modifie progressivement l’endothélium de la valve aortique, ce qui engendre l’expression de biomarqueurs spécifiques aux tissus et à la maladie. On rapporte dans cet étude, l’utilisation de la technique de sélection in vivo par phage display d’une librairie de peptides aléatoires afin de trouver de nouveaux peptides candidats qui se lieraient à des biomarqueurs spécifiques à la valve aortique malade d’une souris. Des souris ATX (LDLr-/-;Tg(hApoB+/+)) âgées atteintes de la SVA ont été utilisées pour la sélection in vivo d’une librairie de peptides aléatoires de 7 acides aminés contraints ou linéaires. Après 4 tours de criblage, on a caractérisé 14 phages différents qui ont été séparés en 5 motifs consensus pour la librairie linéaire et 11 phages différents qui représentent 5 différents motifs consensus pour la libraire de peptides contraints. La spécificité de 4 phages candidats de la librairie linéaire et de 5 phages de la librairie contrainte a été étudiée par l’immunomarquage des peptides d’intérêt exprimés par les phages sur les coupes de tissus de la valve aortique malade par rapport aux tissus contrôles du foie, du rein, de la rate, du ventricule et du poumon. Parmi eux, 6 phages représentent des peptides candidats intéressants qui ont besoin d’être testés davantage pour évaluer leur spécificité in vivo à la valve. Bien qu’il reste encore de la validation à effectuer, les peptides candidats spécifiques trouvés peuvent représenter des agents moléculaires d’imagerie utiles ou des transporteurs dans la livraison de drogue qui ciblent la valve aortique malade.

Tricuspid valve dysplasia and Ebstein's anomaly in dogs: case report

Dois casos de displasia da valva tricúspide são relatados neste trabalho. Os cães foram avaliados devido à fraqueza e presença de ascite. em ambos os casos, o exame ecocardiográfico mostrou insuficiência tricúspide e, em um deles, a inserção dos folhetos da valva tricúspide encontrava-se deslocada para baixo do ventrículo direito, caracterizando a anomalia de Ebstein. A terapia medicamentosa para insuficiência cardíaca congestiva foi iniciada, mas um dos animais veio a óbito subitamente alguns dias após o diagnóstico. O outro cão, apesar de inicialmente ter apresentado melhora significativa do quadro clínico, apresentou morte súbita. A necropsia dos animais revelou dilatação atrioventricular direita e folhetos tricúspides espessados. As características clínicas, métodos de diagnóstico e terapia medicamentosa são discutidas neste artigo.

Dysautonomia and ventricular dysfunction in the indeterminate form of Chagas disease

Background: the associations between autonomic function and biventricular function in patients with the indeterminate form of Chagas disease remains to be elucidated.Methods: In 42 asymptornatic patients and 19 healthy volunteers, the autonomic function was assessed by time domain indices of heart rate variability (HRV), analyzed for 24 h; the right ventricular function was assessed by fraction area change, right ventricle shortening, and systolic excursion of the tricuspid valve; and the left ventricular function was assessed by ejection fraction and transmittal flow velocities. Data were expressed as mean SD or medians (including the lower quartile and upper quartile). Groups were compared by Student's t or Mann-Whitney U test. Autonomic and ventricular function were correlated by Pearson's or Spearman's correlation coefficient. The level of significance was 5%.Results: Right and left ventricular systolic function indexes were comparable between groups. Transmittal flow velocities were decreased in the Chagas disease group (p < 0.05). The patients presented impaired HRV as indicated by the values of SDNN-day (80 (64-99) ms vs. 98 (78-127) ms; p = 0.045), SDNNI-24 It (54 (43-71) vs. 65 (54-105) ms; p = 0.027), SDNNI-day (49 (42-64) vs. 67 (48-76) ms; p = 0.045), pNN50-day (2.2 (0.7-5)% vs. 10 (3-11)%; p = 0.033); and pNN50-24 It (3 (1-7)% vs. 12 (8-19)%; p = 0.013). There were no correlations between the left ventricular diastolic indices and autonomic dysfunctional indices (p > 0.05).Conclusion: Patients with the indeterminate form of Chagas disease have both dysautonomia, and left ventricular diastolic dysfunction. However, the right ventricular function is preserved. Importantly, ventricular diastolic dysfunction and dysautonomia. are independent phenomena. (c) 2005 Elsevier B.V.. All rights reserved.

Comparação da ocorrência de complicações tromboembólicas e hemorrágicas em pacientes portadores de prótese valvares cardíacas mecânicas com um e dois folhetos na posição mitral

Introdução: Pacientes portadores de próteses valvares cardíacas mecânicas devem medicados continuamente com anticoagulantes orais para evitar acidentes tromboembólicos. Estes pacientes são avaliados continuamente para o controle da anticoagulação oral. Objetivo: Comparar a ocorrência de complicações tromboembólicas e hemorrágicas em portadores de próteses valvares cardíacas mecânicas de um (mono) e de dois (bi) folhetos na posição mitral em terapêutica anticoagulante. Métodos: Foram estudados, no intervalo de 10 anos, 117 pacientes portadores de prótese na posição mitral, sendo 48 com próteses de folheto único e 69 de folheto duplo. Avaliou-se a ocorrência de complicações tromboembólicas e hemorrágicas de grau maior e menor de acordo com a gravidade. Os resultados estão apresentados sob forma de estudo atuarial e de frequência linearizada de ocorrência de eventos. Resultados: As curvas atuariais mostraram que, ao longo do tempo, os pacientes portadores de próteses valvares monofolheto estiveram menos livres de complicações tromboembólicas que os pacientes com próteses bifolheto, enquanto que, estes últimos (bifolheto) estiveram menos livres de acidentes hemorrágicos. As frequências linearizadas de ocorrência para tromboembolismo foram maiores nos pacientes com próteses monofolheto. Nos episódios hemorrágicos as taxas foram maiores para os portadores de próteses bifolheto. Conclusão: Os portadores de próteses valvares cardíacas monofolheto mostraram-se mais propensos à ocorrência de acidentes tromboembólicos graves em relação aos com próteses bi folheto. Os pacientes com prótese bifolheto apresentaram maior sangramento que os pacientes com prótese monofolheto, no entanto, esta diferença se restringiu aos sangramentos de pouca gravidade.

Comparison between multiplanar and rendering modes in the assessment of fetal atrioventricular valve areas by 3D/4D ultrasonography

Objective: To compare the agreement of multiplanar and rendering modes in the assessment fetal atrioventricular valves (mitral and tricuspid) areas by three-dimensional (3D) ultrasonography using the software spatio-temporal image correlation (STIC). Methods: We conducted a prospective cross-sectional study with normal pregnant women, with single fetuses, between 18-33 weeks. To measure the areas, we used the plan of four-chamber view. In the case of multiplanar, the plane was rotated on the axis "Z" form the heart to position at 9h. For rendering, the green line (region of interest - ROI) was placed from the atria of the heart perpendicular to the crux. The agreement was assessed by a Bland-Altman (limits of agreement) using the relative difference between the measures: ((rendering mode) - (multiplanar mode)) / (average). Results: 328 fetuses were evaluated. We have not identified the occurrence of systematic error between methods: the average relative difference was 1.62% (-2.07% to 5.32%, confidence interval 95%) in the mitral and 1.77% (- 1.08% to 4.62%) in the tricuspid valve. The limits of agreement between methods were -65.26% to 68.51% for the mitral and -49.91% to 53.45% for the tricuspid. Conclusions: There was no systematic error between modes and thus the observed values for the area of fetal atrioventricular valves can be used for comparisons needs to be corrected. However, relatively large variations may be observed when repeating the measurement area by different modes.

Balloon Aortic Valvuloplasty as Bridge-to-Decision in High Risk Patients with Severe Aortic Valve Stenosis

Background. A sizable group of patients with symptomatic aortic stenosis (AS) can undergo neither surgical aortic valve replacement (AVR) nor transcatheter aortic valve implantation (TAVI) because of clinical contraindications. The aim of this study was to assess the potential role of balloon aortic valvuloplasty (BAV) as a “bridge-to-decision” in selected patients with severe AS and potentially reversible contraindications to definitive treatment. Methods. We retrospectively enrolled 645 patients who underwent first BAV at our Institution between July 2007 and December 2012. Of these, the 202 patients (31.2%) who underwent BAV as bridge-to-decision (BTD) requiring clinical re-evaluation represented our study population. BTD patients were further subdivided in 5 groups: low left ventricular ejection fraction; mitral regurgitation grade ≥3; frailty; hemodynamic instability; comorbidity. The main objective of the study was to evaluate how BAV influenced the final treatment strategy in the whole BTD group and in its single specific subgroups. Results. Mean logistic EuroSCORE was 23.5±15.3%, mean age was 81±7 years. Mean transaortic gradient decreased from 47±17 mmHg to 33±14 mmHg. Of the 193 patients with BTD-BAV who received a second heart team evaluation, 72.5% were finally deemed eligible for definitive treatment (25.4%for AVR; 47.2% for TAVI): respectively, 96.7% of patients with left ventricular ejection fraction recovery; 70.5% of patients with mitral regurgitation reduction; 75.7% of patients who underwent BAV in clinical hemodynamic instability; 69.2% of frail patients and 68% of patients who presented relevant comorbidities. 27.5% of the study population was deemed ineligible for definitive treatment and treated with standard therapy/repeated BAV. In-hospital mortality was 4.5%, cerebrovascular accident occurred in 1% and overall vascular complications were 4% (0.5% major; 3.5% minor). Conclusions. Balloon aortic valvuloplasty should be considered as bridge-to-decision in high-risk patients with severe aortic stenosis who cannot be immediate candidates for definitive percutaneous or surgical treatment.

Recent developments for surgical aortic valve replacement: the concept of sutureless valve technology

Aortic stenosis has become the most frequent type of valvular heart disease in Europe and North America and presents in the large majority of patients as calcified aortic stenosis in adults of advanced age. Surgical aortic valve replacement has been recognized to be the definitive therapy which improves considerably survival for severe aortic stenosis since more than 40 years. In the most recent period, operative mortality of isolated aortic valve replacement for aortic stenosis varies between 1–3% in low-risk patients younger than 70 years and between 4 and 8% in selected older adults. Long-term survival following aortic valve replacement is close to that observed in a control population of similar age. Numerous observational studies have consistently demonstrated that corrective surgery in symptomatic patients is invariably followed by a subjective improvement in quality of life and a substantial increase in survival rates. More recently, transcatheter aortic valve implantation (TAVI) has been demonstrated to be feasible in patients with high surgical risk using either a retrograde transfemoral or transsubclavian approach or an antegrade, transapical access. Reported 30-day mortality ranges between 5 and 15%) and is acceptable when compared to the risk predicted by the logistic EuroSCORE (varying between 20 and 35%) and the STS Score, although the EuroScore has been shown to markedly overestimate the effective operative risk. One major concern remains the high rate of paravalvular regurgitation which is observed in up to 85% of the patients and which requires further follow-up and critical evaluation. In addition, long-term durability of these valves with a focus on the effects of crimping remains to be addressed, although 3-5 year results are promising. Sutureless biological valves were designed to simplify and significantly accelerate the surgical replacement of a diseased valve and allow complete excision of the calcified native valve. Until now, there are 3 different sutureless prostheses that have been approved. The 3f Enable valve from ATS-Medtronic received CE market approval in 2010, the Perceval S from Sorin during Q1 of 2011 and the intuity sutureless prosthesis from Edwards in 2012. All these devices aim to facilitate valve surgery and therefore have the potential to decrease the invasivness and to shorten the conventional procedure without compromise in term of excision of the diseased valve. This review summarizes the history and the current knowledge of sutureless valve technology.

Transcatheter aortic valve implantation: the procedure

Transcatheter aortic valve implantation (TAVI) for the treatment of symptomatic severe aortic stenosis has emerged as an effective treatment for high risk patients. In 2002 TAVI was performed for the first time in a human by Alain Cribier, using an antegrade access approach via the femoral vein, crossing the intra-atrial septum after puncture and passing the native aortic valve in the direction of blood flow. This technically demanding approach was subsequently replaced by retrograde transfemoral arterial access. For patients with severe peripheral vascular disease or inadequately sized femoral arteries, the transapical route provides an alternative route with antegrade access to the aortic valve via puncture of the anterolateral wall of the left ventricle. The transsubclavian access approach using most frequently the left subclavian artery and direct transaortic access have been introduced more recently and attest to the versatility of TAVI in terms of access site. This article will focus on the different access site options available to operators, provide a step-by-step guide through the procedure, and a detailed description of the technological evolution of transcatheter heart valve systems.

Impact of left ventricular hypertrophy late after aortic valve replacement for aortic stenosis on cardiovascular morbidity and mortality

AIMS: The goal of this study was to assess the prevalence of left ventricular (LV) hypertrophy in patients with aortic stenosis late (>6 months) after aortic valve replacement and its impact on cardiac-related morbidity and mortality. METHODS AND RESULTS: In a single tertiary centre, echocardiographic data of LV muscle mass were collected. Detailed information of medical history and angiographic data were gathered. Ninety-nine of 213 patients (46%) had LV hypertrophy late (mean 5.8 +/- 5.4 years) after aortic valve replacement. LV hypertrophy was associated with impaired exercise capacity, higher New York Heart Association dyspnoea class, a tendency for more frequent chest pain expressed as higher Canadian Cardiovascular Society class, and more rehospitalizations. 24% of patients with normal LV mass vs. 39% of patients with LV hypertrophy reported cardiac-related morbidity (p = 0.04). In a multivariate logistic regression model, LV hypertrophy was an independent predictor of cardiac-related morbidity (odds ratio 2.31, 95% CI 1.08 to 5.41), after correction for gender, baseline ejection fraction, and coronary artery disease and its risk factors. Thirty seven deaths occurred during a total of 1959 patient years of follow-up (mean follow-up 9.6 years). Age at aortic valve replacement (hazard ratio 1.85, 95% CI 1.39 to 2.47, for every 5 years increase in age), coexisting coronary artery disease at the time of surgery (hazard ratio 3.36, 95% CI 1.31 to 8.62), and smoking (hazard ratio 4.82, 95% CI 1.72 to 13.45) were independent predictors of overall mortality late after surgery, but not LV hypertrophy. CONCLUSIONS: In patients with aortic valve replacement for isolated aortic stenosis, LV hypertrophy late after surgery is associated with increased morbidity.

[Treatment of the aortic valve and ascending aorta. The significance of reconstructive methods on the aortic root]

BACKGROUND AND OBJECTIVE: The standard surgical repair of disease of the aortic valve and the ascending aorta has been combined replacement, which includes the disadvantage of inserting a mechanical valve. We have investigated an individualized approach which preserves the native valve. PATIENTS AND METHODS: Between October 1995 and October 1997, a consecutive total of 101 patients (72 men, 29 women, aged 21-83 years) underwent operations for disease of the ascending aorta: aortic dissection type A in 34 patients, aneurysmal dilatation in 67. Dilatation of the aortic arch was associated with aortic regurgitation in 58 patients. There were 11 patients with aortic valve stenosis or previously implanted aortic valve prosthesis among a total of 46 whose aortic valve was replaced (group II). Supracommissural aortic replacement with a Dacron tube was performed in 16 patients (group I) with normal valve cusps and an aortic root diameter < 3.5 cm. In 28 patients with an aortic root diameter of 3.5-5.0 cm the aortic root was remodelled (group III). Resuspension of the native aortic valve was undertaken in 11 patients with aortic root dilatation of > 5.0 cm (group IV). RESULTS: Operative intervention was electively performed in 72 patients, without any death. Of 29 patients operated as an emergency for acute type A dissection four died (14%). In 55 of the 58 patients with aortic regurgitation in proved possible to preserve native aortic valve (95%). In the early postoperative phase and after an average follow-up time of 11.8 months, transthoracic echocardiography demonstrated good aortic valve function, except in one patient each of groups III and IV who developed aortic regurgitation grades I or II. CONCLUSION: The described individualized approach makes it possible to preserve the native aortic valve in most patients with aortic regurgitation, at a low risk. Follow-up observations so far indicate good results of the reconstruction.

Risk of acute kidney injury in patients with severe aortic valve stenosis undergoing transcatheter valve replacement

BACKGROUND: Transcatheter aortic valve implantation (TAVI) for high-risk and inoperable patients with severe aortic stenosis is an emerging procedure in cardiovascular medicine. Little is known of the impact of TAVI on renal function. METHODS: We analysed retrospectively renal baseline characteristics and outcome in 58 patients including 2 patients on chronic haemodialysis undergoing TAVI at our institution. Acute kidney injury (AKI) was defined according to the RIFLE classification. RESULTS: Fifty-eight patients with severe symptomatic aortic stenosis not considered suitable for conventional surgical valve replacement with a mean age of 83 +/- 5 years underwent TAVI. Two patients died during transfemoral valve implantation and two patients in the first month after TAVI resulting in a 30-day mortality of 6.9%. Vascular access was transfemoral in 46 patients and transapical in 12. Estimated glomerular filtration rate (eGFR) increased in 30 patients (56%). Fifteen patients (28%) developed AKI, of which four patients had to be dialyzed temporarily and one remained on chronic renal replacement therapy. Risk factors for AKI comprised, among others, transapical access, number of blood transfusions, postinterventional thrombocytopaenia and severe inflammatory response syndrome (SIRS). CONCLUSIONS: TAVI is feasible in patients with a high burden of comorbidities and in patients with pre-existing end-stage renal disease who would be otherwise not considered as candidates for conventional aortic valve replacement. Although GFR improved in more than half of the patients, this benefit was associated with a risk of postinterventional AKI. Future investigations should define preventive measures of peri-procedural kidney injury.

[Role of coronary artery bypass grafting in the treatment of coronary artery disease - a well-balanced information of the patients and objective decision making are welcome]

Most recently discussion about the optimal treatment for different subsets of patients suffering from coronary artery disease has re-emerged, mainly because of the uncertainty caused by doctors and patients regarding the phenomenon of unpredictable early and late stent thrombosis. Surgical revascularization using multiple arterial bypass grafts has repeatedly proven its superiority compared to percutaneous intervention techniques, especially in patients suffering from left main stem disease and coronary 3-vessels disease. Several prospective randomized multicenter studies comparing early and mid-term results following PCI and CABG have been really restrictive, with respect to patient enrollment, with less than 5% of all patients treated during the same time period been enrolled. Coronary artery bypass grafting allows the most complete revascularization in one session, because all target coronary vessels larger than 1 mm can be bypassed in their distal segments. Once the patient has been turn-off for surgery, surgeons have to consider the most complete arterial revascularization in order to decrease the long-term necessity for re-revascularization; for instance patency rate of the left internal thoracic artery grafted to the distal part left anterior descending artery may be as high as 90-95% after 10 to 15 years. Early mortality following isolated CABG operation has been as low as 0.6 to 1% in the most recent period (reports from the University Hospital Berne and the University Hospital of Zurich); beside these excellent results, the CABG option seems to be less expensive than PCI with time, since the necessity for additional PCI is rather high following initial PCI, and the price of stent devices is still very high, particularly in Switzerland. Patients, insurance and experts in health care should be better and more honestly informed concerning the risk and costs of PCI and CABG procedures as well as about the much higher rate of subsequent interventions following PCI. Team approach for all patients in whom both options could be offered seems mandatory to avoid unbalanced information of the patients. Looking at the recent developments in transcatheter valve treatments, the revival of cardiological-cardiosurgical conferences seems to a good option to optimize the cooperation between the two medical specialties: cardiology and cardiac surgery.

Pulmonary venous flow velocity patterns in 404 individuals without cardiovascular disease

OBJECTIVE To determine the pulmonary venous flow velocity (PVFV) values in a large normal population. DESIGN Prospective study in consecutive individuals. SETTING University hospital. METHODS Among 404 normal individuals, the flow velocity pattern in the right upper pulmonary vein was recorded in 315 subjects using transthoracic echocardiography, and in both upper pulmonary veins in 100 subjects using transoesophageal echocardiography. Subjects were divided into five age groups. The PVFV values were compared between transthoracic and transoesophageal echocardiography within the age groups, and intraindividually between the right and left upper pulmonary veins in transoesophageal echocardiography. RESULTS Normal PVFV values for the right upper pulmonary vein in transthoracic and transoesophageal echocardiography are presented. The duration of flow reversal at atrial contraction was overestimated using transthoracic echocardiography (mean (SD): 96 (21) ms in transoesophageal echocardiography, 120 (28) ms in transthoracic echocardiography, p < 0.0001). Systolic to diastolic peak flow velocity ratio (S:D) increased earlier with advancing age with transoesophageal echocardiography than with transthoracic echocardiography. Similar results were found for the corresponding time-velocity integrals. Data from the left and right upper pulmonary veins differed with respect to onset and deceleration of flow velocities, but not for flow durations or peak velocities. CONCLUSIONS Normal PVFV values generally show a wide range. The data presented will be of value in assessing left ventricular diastolic function and mitral regurgitation using the PVFV pattern.