Leflunomide-induced pulmonary arterial hypertension: Case report and review of literature.

Leflunomide, an isoxazole derivative, is a disease-modifying antirheumatic drug, that has successfully been used for the treatment of rheumatoid arthritis and psoriatic arthritis as a feasible alternative to methotrexate. Among side effects, pulmonary arterial hypertension (PAH) has been described in a few case reports.We present a 55-year-old woman treated with leflunomide for psoriatic spondyloarthritis who consulted our hospital because of progressive exertional dyspnea. Clinical examination found signs of right heart failure and severe pre-capillary pulmonary hypertension (PH) was diagnosed by right heart catheterization. All investigations for pre-capillary PH were negative and a diagnosis of severe PAH was thus established. Due to previous evidence of the association of leflunomide with PAH, the drug was stopped and upfront dual combination therapy with pulmonary vasodilators was initiated. The patient's condition rapidly improved with significant improvement in exercise tolerance and normalization of echocardiographic right ventricular systolic pressure within three months of treatment. Learning objective: Pulmonary arterial hypertension (PAH) is a rare disease and drug-induced causes account for only a small percentage of these patients. In recent years, new drugs have been identified or suspected as potential risk factors for PAH. Among these, leflunomide, a disease-modifying antirheumatic drug, has been associated with PAH only in a few case reports. An accurate drug history is strongly recommended for all patients in which a PAH is newly diagnosed.

[Appropriateness in echocardiography and clinical priority classification criteria: a proposal from the Italian Society of Cardiovascular Echography]. / Appropriatezza dell'esame ecocardiografico e definizione delle classi di priorità: una proposta della Società Italiana di Ecografia Cardiovascolare.

One of the main tasks of a scientific society is to define the theoretical bases and appropriate management strategies with the aim to maintain a high-quality diagnostic and therapeutic standard. As far as echocardiography is concerned, the task of the Italian Society of Cardiovascular Echography is to provide appropriate, complete, and useful echocardiographic tests for clinical application, as well as procedural, technological, organizational and economic indications to be adopted in clinical practice. In addition, there is an increasing need for regulating access to echocardiographic assessment according to clinical priority, because of the huge proportion of patients who should undergo a first or follow-up echocardiographic evaluation. The aim of this document is to implement appropriateness in echocardiography for the study and follow-up of cardiovascular diseases, and to optimize demand on the basis of clinical priority classification criteria outlined by the scientific societies and used by the National Health Service. Besides cardiovascular diseases, this document also addresses other diseases that often require echocardiographic investigation, such as liver diseases, connective tissue diseases, endocrine diseases, peripheral vascular and oncological diseases. Although not included in the previous guidelines, clinical priority and followup criteria are defined also for these groups of diseases according to the available literature. In conclusion, this document aims at guaranteeing access to the diagnostic echocardiographic procedures provided by the National Health Service to the general population, with practical indications on how to solve the problem of waiting lists.

[Permanent atrial fibrillation and heart failure: radiofrequency ablation of atrioventricular junction and cardiac resynchronization therapy: review of the literature and of the new techniques for echocardiographic assessment]. / Fibrillazione atriale permanente e scompenso cardiaco: ablazione a radiofrequenza della giunzione atrioventricolare e terapia di resincronizzazione cardiaca. Revisione della letteratura e delle nuove tecniche di valutazione ecocardiografica.

Radiofrequency ablation of atrioventricular junction plus pacing therapy ("ablate and pace") is an effective non-pharmacological therapy in patients with medically refractory permanent atrial fibrillation and heart failure. However, the chronic right ventricular pacing may result in regional wall motion abnormalities and adverse hemodynamic effects. These findings imply that patients with permanent atrial fibrillation who undergo "ablate and pace" may benefit from cardiac resynchronization therapy. The review of both observational and randomized studies suggests an important role of biventricular pacing combined with atrioventricular junction ablation only in patients with severe reduction of left ventricular ejection fraction and advanced heart failure. In all other patients with permanent atrial fibrillation, the comparison of conventional right ventricular pacing with respect to cardiac resynchronization therapy showed conflicting results. The assessment of cardiac dyssynchrony by means of new echocardiographic technology, including three-dimensional analysis, may improve the selection of the best pacing modality in patients undergoing "ablate and pace" for drug refractory permanent atrial fibrillation.

Real-time three-dimensional echocardiography: technological gadget or clinical tool?

The complex anatomy of cardiac structures requires three-dimensional spatial orientation of images for a better understanding of structure and function, thereby improving image interpretation. Real-time three-dimensional echocardiography is a recently developed technique based on the design of an ultrasound transducer with a matrix array that rapidly acquires image data in a pyramidal volume. The simultaneous display of multiple tomographic images allows three-dimensional perspective and the anatomically correct examination of any structure within the volumetric image. As a consequence, it is less operator-dependent and hence more reproducible. Dedicated software systems and technologies are based on high-performance computers designed for graphic handling of three-dimensional images by providing possibilities beyond those obtainable with echocardiography. This methodology allows simultaneous display of multiple superimposed planes in an interactive manner as well as a quantitative assessment of cardiac volumes and ventricular mass in a three-dimensional format without a pre-established assumption of cardiac chamber geometry. In addition, myocardial contraction and/or perfusion abnormalities are clearly identified. Finally, real-time three-dimensional colour Doppler flow mapping enables complete visualisation of the regurgitant jet and new ways of assessing regurgitant lesion severity. Thus, this technique expands the abilities of non-invasive cardiology and may open new doors for the evaluation of cardiac diseases. In this article, current and future clinical applications of real-time three-dimensional echocardiography are reviewed.

Clinical and hemodynamic implications of supra-annular implant of biological aortic valves.

The use of stented bioprostheses in elderly patients with degenerative aortic stenosis, despite being desirable, raises concerns about the harmful effects of residual obstruction to left ventricular outflow. To overcome this limitation new stented and stentless bioprostheses have been designed for supra-annular implant. However, the actual hemodynamic advantage of supra-annular implant over the intra-annular one remains incompletely understood. This review focuses on the geometry of biological valve prostheses designed for supra-annular implant and its implications for the echocardiographic assessment of valve hemodynamics. Available data about the hemodynamic performance of these valves implanted in the supra-annular position in comparison with the usual intra-annular implant are also reviewed. Other issues related to biological heart valve performance, such as biomaterials, tissue mechanics, durability, and clinical outcome are not addressed in this review.

Improved delineation of morphological features of arrhythmogenic right ventricular cardiomyopathy with the use of contrast-enhanced echocardiography.

A case of an already diagnosed arrhythmogenic right ventricular cardiomyopathy in which the use of contrast improved the echocardiographic characterization of morphologic abnormalities of the right ventricle is reported.

Stented bioprosthetic valve hemodynamics: is the supra-annular implant better than the intra-annular?

BACKGROUND AND AIM OF THE STUDY: The use of stented bioprostheses for aortic valve replacement (AVR) in elderly patients with a small aortic annulus may result in unsatisfactory hemodynamic performance of the prosthesis. To overcome this limitation, new bioprostheses have been designed for complete supra-annular implantation, but the actual hemodynamic advantage of the supra-annular implant over the intra-annular has not been fully investigated. Accordingly, the hemodynamic performance of the same stented bioprosthesis (except for sewing ring design) implanted in the supra-annular and conventional intra-annular seating was compared. METHODS: Twenty-two patients received an intra-annular implant, and 38 a supra-annular implant. Age (74 +/- 5 versus 76 +/- 5 years, p = 0.54), gender (55% versus 50% males, p = 0.79) and body surface area (1.74 +/- 0.2 versus 1.81 +/- 0.2 m2, p = 0.13) were similar in both subgroups, who underwent echocardiography at 8 +/- 2 and 6 +/- 2 months after surgery, respectively (p = 0.09). RESULTS: The two patient subgroups had similar preoperative left ventricular outflow tract diameters (2.06 +/- 0.2 and 2.1 +/- 0.2 cm; p = 0.62), average size of implanted prosthesis (21.0 and 21.3 mm; p = 0.44) and mean transprosthetic flow rate (246 +/- 70 and 218 +/- 58 ml/s; p = 0.12). Mean (8 +/- 3 and 19 +/- 8 mmHg, p < 0.0001), and peak (17 +/- 6 and 40 +/- 13 mmHg; p < 0.0001) transprosthetic gradients were lower, and mean effective orifice area (EOA) (1.78 +/- 0.4 and 1.45 +/- 0.5 cm2, p = 0.006) was higher in patients with supra-annular implants than in those with intraannular. The incidence of patient-prosthesis mismatch (EOA index < 0.85 cm2/m2) decreased from 50% to 34% (p < 0.0001), with no case of severe mismatch using the supra-annular implant. During follow up, a left ventricular mass reduction occurred in patients with supra-annular implants (from 225 +/- 110 to 173 +/- 59 g/m2; p < 0.03), but not in patients with intra-annular implants (173 +/- 62 and 186 +/- 64 g/m2; p = 0.87) CONCLUSION: The study results showed that, compared to intra-annular implantation, supra-annular implantation of bioprosthetic stented valves in the aortic position was associated with a significantly better hemodynamic performance of the prosthesis and significant regression of left ventricular hypertrophy.

[Selection of patients undergoing cardiac resynchronization therapy: role of echocardiography]. / Ruolo dell'ecocardiografia nella selezione dei pazienti da candidare alla terapia di resincronizzazione ventricolare.

Patients with heart failure, marked systolic dysfunction and dys-synchronous myocardial contraction are at increased risk for exacerbated pump failure and arrhythmias, and suffer higher mortality rates. In these patients, cardiac resynchronization therapy (CRT), achieved by a biventricular pacing, can lead to clinical improvement, reverse left ventricular remodeling and prolonged survival, although a substantial subset of non-responders has been reported. The electrocardiographic QRS width does not predict long-term CRT benefit, while direct measures of mechanical dyssynchrony obtained by various ultrasound techniques have been shown to have a better predictive value. However, currently there is no consensus on the optimal ultrasound technique to use for assessing mechanical dyssynchrony and select candidates for CRT. In this review, the clinical role of both conventional and new ultrasound techniques applied to the study of cardiac dyssynchrony will be discussed, focusing on patient selection for CRT.