Doppler echocardiography assessment of impaired left ventricular filling in patients with right ventricular pressure overload due to primary pulmonary hypertension

In patients with primary pulmonary hypertension, competition between the right and left ventricles for the limited pericardial space results in distortion of left ventricular geometry reflected in displacement of the ventricular septum toward the left ventricular cavity. Left ventricular shape is most dramatically deranged at end-systole and early diastole, suggesting the possibility that the distribution of left ventricular diastolic filling might be altered. To investigate this hypothesis, nine patients with primary pulmonary hypertension and nine normal individuals were studied with echocardiographic techniques. Left ventricular isovolumic relaxation time was significantly prolonged in patients with primary pulmonary hypertension by comparison with normal individuals (129 ± 36 versus 53 ± 9 ms, p < 0.005) and the fraction of the transmitral flow velocity integral occurring in the first half of diastole was significantly less than in normal individuals (38 ± 14% versus 70 ± 9%, p < 0.005). Measurement of fractional changes in short-axis left ventricular cavity area similarly demonstrated that in patients with primary pulmonary hypertension fractional early diastolic cavity expansion (32 ± 11%) was significantly less than in normal individuals (78 ± 9%, p < 0.005).In patients with primary pulmonary hypertension, the ventricular septum was abnormally flattened toward the left ventricular cavity at end-systole (normalized septal curvature 0.04 ± 0.19) and remained that way throughout early diastolic filling but returned toward normal at end-diastole (normalized septal curvature 0.68 ± 0.19, p < 0.005). Thus, in patients with primary pulmonary hypertension end-systolic and early diastolic deformation of the left ventricle by septal flattening toward the left ventricular cavity is associated with relative underfilling of the left ventricle in early diastole and redistribution of left ventricular filling into late diastole. The reliance on late diastolic filling and atrial systole to maintain left ventricular preload in primary pulmonary hypertension may have important implications for the use of vasodilators in this disease

Doppler echocardiographic demonstration of the differential effects of right ventricular pressure and volume overload on left ventricular geometry and filling

AbstractTo compare the effects of isolated right ventricular pressure and volume overload on left ventricular diastolic geometry and filling, 11 patients with primary pulmonary hypertension, 11 patients with severe tricuspid regurgitation due to tricuspid valve resection and 11 normal subjects were studied with use of Doppler echocardiography techniques. Right ventricular systolic overload in primary pulmonary hypertension resulted in substantial leftword ventricular septal shift that was most marked at end-systole and early diastole and decreased substantially by end-diastole. Right ventricular diastolic overload after tricuspid valve resection resulted in maximal leftward ventricular septal shift at end-diastole sparing end-systole and early diastole. The early diastolic distortion of left ventricular geometry associated with right ventricular pressure overload resulted in prolongation of isovolumetric relaxation of the left ventricle (129 ± 39 ms) and a reduction in early diastolic finding compared with values in normal subjects.Late diastolic distortion of left ventricular geometry associated with right ventricular volume overload had no influence on the duration of left ventricular isovolumetric relaxatoon (52 ± 32 ms) but caused a reduction in the atrial systolic contribution to late distolic filling of the left ventricle compared with values in normal sujects. In patients with right ventricular pressure overload, 52 ± 16% of left ventricular filling occurred in early diastole compared with 78 ± 11% in patients with right ventricular volume overload (p < 0.001). The differential effects of systolic and diastolic right ventricular overload on the pattern of left ventricular filling appear to bt related to the timing of leftward ventricular septal displacement

800-5 Improving Accuracy of Ultrafast Computed Tomography in the Detection of Angiographically Significant Coronary Artery Disease

In differentiating coronary calcium from artifact by ultrafast computed tomography (UFCT), many different thresholds have been proposed. UFCT has demonstrated a high sensitivity and only modest specificity to detect coronary calcifications when compared to angiography. The Agatston method is most widely used today, utilizing a minimum CT number of 130 Hounsfield units (HU). In an attempt to improve specificity without markedly reducing sensitivity, we evaluated 272 coronary vessels from 68 patients with angiography and UFCT coronary scanning. All patients underwent coronary angiography for clinical indications, and had UFCT scanning done within three months of the angiogram. A blinded reader evaluated all the UFCT scans. We then varied the minimum CT number to assess whether 130 HU was truly the best threshold. Sensitivity, specificity and accuracy for different thresholds are listed.Threshold130 HU150 HU170 HU200 HUSensitivity95%92%89%87%Specificity65%72%75%78%Accuracy72%77%78%79%The results above indicate that 130 HU is too low a threshold to maximize accuracy of this test when compared with angiography. Sensitivity is reduced as the threshold is improved, however this result is not significant (p=0.61). The improved specificity from 130 to 150 represents a significant improvement (p&lt;0.0001), although a larger study must be performed before widespread use of this new threshold is employed

Antinuclear antibodies in primary pulmonary hypertension

The association of positive antinuclear antibodies with the clinical and hemodynamic features of 43 patients with primary pulmonary hypertension and 16 patients with secondary pulmonary hypertension was investigated. Each patient had determinations of antinuclear antibodies using a KB cell substrate immunofluorescent test. Of the patients with primary pulmonary hypertension, 40% had positive antinuclear antibodies at titers of 1:80 dilutions or greater. There were no differences between patients with primary pulmonary hypertension and positive antinuclear antibodies compared with those with negative antinuclear antibodies in relation to clinical or hemodynamic status. A 6% incidence raie of antinuclear antibodies was found in patients with secondary pulmonary hypertension, similar to that in the normal population.The clinical, hemodynamic, serologic and histologic similarity between patients with primary pulmonary hypertension and those with unexplained pulmonary hypertension associated with collagen vascular disorders suggests that primary pulmonary hypertension in some patients may represent a collagen vascular disease confined to the lungs. The frequency of positive antinuclear antibody tests would place primary pulmonary hypertension between rheumatoid arthritis and scleroderma in the spectrum of collagen vascular diseases. Further studies are necessary, however, before one might expect that immunosuppressive therapy would be beneficial to these patients

Tadalafil for the Treatment of Pulmonary Arterial Hypertension A Double-Blind 52-Week Uncontrolled Extension Study

ObjectivesThe aim of this study was to evaluate the long-term safety and durability of efficacy of tadalafil for pulmonary arterial hypertension.BackgroundTadalafil is an oral phosphodiesterase-5 inhibitor approved for PAH treatment. In the multicenter, placebo-controlled, randomized, 16-week PHIRST (Pulmonary Arterial Hypertension and Response to Tadalafil) study, tadalafil 40 mg improved exercise capacity and delayed clinical worsening.MethodsEligible patients from PHIRST received once-daily tadalafil 20 mg (T20 mg) or 40 mg (T40 mg) (n = 357) in the double-blind, 52-week, uncontrolled extension study (PHIRST-2); 293 patients completed PHIRST-2. Durability of efficacy was explored using the 6-min walk distance (6MWD) test. Clinical worsening and changes in World Health Organization functional class were evaluated.ResultsThe safety profile of tadalafil in PHIRST-2 was similar to that in PHIRST, with typical phosphodiesterase-5 inhibitor adverse events. The 6MWDs achieved in PHIRST for the subset of patients receiving T20 mg and T40 mg in both PHIRST and PHIRST-2 (406 ± 67 m [n = 52] and 413 ± 81 m [n = 59] at PHIRST-2 enrollment, respectively) were maintained at PHIRST-2 completion (415 ± 80 m [n = 51] and 410 ± 78 m [n = 59], respectively). Numerically fewer patients who were on T40 mg in PHIRST and PHIRST-2 experienced World Health Organization functional class deterioration (6% [n = 5]) compared with those randomized to T20 mg (9% [n = 7]) across both studies. Post hoc analyses showed that background bosentan use and higher 6MWD at PHIRST baseline were associated with fewer clinical worsening events.ConclusionsLong-term treatment with tadalafil was well tolerated in patients with pulmonary arterial hypertension. In patients receiving either T20 mg or T40 mg, the improvements in 6MWD demonstrated in the 16-week PHIRST study appeared sustained for up to 52 additional weeks of treatment in PHIRST-2. (Pulmonary Arterial Hypertension and Response to Tadalafil Study; NCT00549302

Evaluating the Benefits of Aphasia Intervention Delivered in Virtual Reality: Results of a Quasi-Randomised Study

Introduction This study evaluated an intervention for people with aphasia delivered in a novel virtual reality platform called EVA Park. EVA Park contains a number of functional and fantastic locations and allows for interactive communication between multiple users. Twenty people with aphasia had 5 weeks’ intervention, during which they received daily language stimulation sessions in EVA Park from a support worker. The study employed a quasi randomised design, which compared a group that received immediate intervention with a waitlist control group. Outcome measures explored the effects of intervention on communication and language skills, communicative confidence and feelings of social isolation. Compliance with the intervention was also explored through attrition and usage data. Results There was excellent compliance with the intervention, with no participants lost to follow up and most (18/20) receiving at least 88% of the intended treatment dose. Intervention brought about significant gains on a measure of functional communication. Gains were achieved by both groups of participants, once intervention was received, and were well maintained. Changes on the measures of communicative confidence and feelings of social isolation were not achieved. Results are discussed with reference to previous aphasia therapy findings

Usefulness of electron beam computed tomography scanning for distinguishing ischemic from nonischemic cardiomyopathy

AbstractObjectives. This study was undertaken to evaluate the ability of electron beam computed tomography (EBCT) to distinguish ischemic from nonischemic causes of cardiomyopathy by evaluating heart failure patients for coronary calcification (CC).Background. The etiology of heart failure, whether coronary-induced or nonischemic, may be difficult to discern clinically. Differentiation of ischemic from nonischemic etiology is clinically important for both therapeutic and prognostic implications. With its ability to noninvasively discern and quantitate coronary artery calcification, EBCT correlates well with angiographic stenosis and thus may be useful in distinguishing ischemic and nonischemic cardiomyopathies.Methods. One hundred and twenty-five patients with cardiomyopathy (ejection fraction <0.40) and known coronary anatomy underwent EBCT coronary scanning to evaluate for CCs within 3 months of coronary angiography.Results. Of the 72 patients who were found to have ischemic cardiomyopathy, 71 patients had CC by EBCT (sensitivity 99%, p < 0.001), mean score 798 ± 899. In comparison, among the 53 patients without significant coronary artery disease (CAD) (nonischemic cardiomyopathy), the mean score was significantly lower (17 ± 51; p < 0.0001), and 44 patients had a CC score of 0 (no CC present). The specificity of EBCT to exclude CAD in patients with cardiomyopathy was 83%, using a threshold CC score of 0, and 92% for scores <80 (p < 0.001). Overall accuracy for determining the etiology of cardiomyopathy (differentiating ischemic from nonischemic) was 92% for this technique.Conclusions. This prospective, blinded study indicates that EBCT detected CC accurately and can noninvasively distinguish between cardiomyopathy because of CAD and nonischemic causes of left ventricular dysfunction