Use of mTOR inhibitors in chronic heart transplant recipients with renal failure: calcineurin-inhibitors conversion or minimization?

BACKGROUND: In the last decade, mTOR inhibitors (mTOR-is) have become the cornerstone of the calcineurin inhibitor (CNI)-reduced/free regimens aimed to the preservation of post-transplant renal function. We compared utility and safety of the total replacement of calcineurin inhibitors with a mTOR-i with a strategy based on calcineurin inhibitor minimization and concomitant use of m-TOR-i. METHODS: In a retrospective multi-center cohort of 394 maintenance cardiac recipients with renal failure (GFR<60 mL/min/1.73 m(2)), we compared 235 patients in whom CNI was replaced with a mTOR-i (sirolimus or everolimus) with 159 patients in whom mTOR-is were used to minimize CNIs. A propensity score analysis was carried out to balance between group differences. RESULTS: Overall, after a median time of 2 years from mTOR-i initiation, between group differences for the evolution of renal function were not observed. In a multivariate adjusted model, improvement of renal function was limited to patients with mTOR-i usage within 5years after transplantation, particularly with the conversion strategy, and in those patients who could maintain mTOR-i therapy. Significant differences between strategies were not found for mortality, infection and mTOR-i withdrawal due to drug-related adverse events. However, conversion group tended to have a higher acute rejection incidence than the minimization group (p=0.07). CONCLUSION: In terms of renal benefits, our results support an earlier use of mTOR-is, irrespective of the strategy. The selection of either a conversion or a CNI minimization protocol should be based on the clinical characteristics of the patients, particularly their rejection risk.

Risk factors associated with cytomegalovirus infection in heart transplant patients: a prospective, epidemiological study.

BACKGROUND: The objectives of this epidemiological, prospective study were to describe the characteristics of cytomegalovirus (CMV) infection in heart transplant (HT) recipients and to identify the variables that may influence the development of CMV viremia and CMV disease in these patients. METHODS: HT recipients ≥18 years of age (n=199) were included in the study. Variables studied included CMV serostatus, immunosuppressive treatment, and administration of anti-CMV prophylaxis. RESULTS: The mean age of the population was 52 years, and 84% were males. Immunosuppressive regimens were administered as induction therapy to 92.5% of patients; 88.5% of patients received calcineurin inhibitors as maintenance therapy. Anti-CMV treatment was given to 59% of 199 patients as prophylaxis (70%), preemptive therapy (10%), or to treat CMV infection (20%). Overall, 43% of patients had at least 1 positive viremia test. No patient with a high-risk serostatus (donor+/recipient-) receiving prophylaxis developed CMV syndrome, and only 2.5% of 199 patients developed CMV invasive disease. Multivariate analysis showed that having a positive donor CMV serostatus was associated with an increased risk of developing CMV viremia (P<0.012), while use of mammalian target of rapamycin (mTOR) inhibitors was associated with a decreased risk (P=0.005). CONCLUSIONS: In a population of HT recipients, the CMV infection rate was similar to that seen in previous studies, but the progression to overt CMV disease was very low. Having a CMV-positive donor was identified as an independent risk factor for developing CMV viremia, while the use of mTOR inhibitors was protective against viremia.

Temporal trends in the use of proliferation signal inhibitors in maintenance heart transplantation: a Spanish multicenter study.

Proliferation signal inhibitors (PSI; sirolimus, everolimus) are being increasingly used in heart transplantation. We performed an observational, retrospective, multicenter study in 9 Spanish centers seeking to describe the clinical context in which a PSI was used among maintenance heart recipients and its evolution over time. We collected a cohort of 548 patients in whom a PSI was prescribed from October 2001 to March 2009. The group was divided into 3 time periods. The use of PSI steeply increased in the 2005-2006 period, remaining stable thereafter. There were no significant differences over time with regard to age, gender, or time from transplantation to the introduction of the PSI. Everolimus usage overtook sirolimus from 2005 on; currently, >90% of the subjects with PSI indications are prescribed everolimus. Compared with earlier periods, patients in the more recent period (October 2006-March 2009) showed less vascular graft disease and better basal renal function, irrespective of the primary indication for the PSI prescription. Also, skin cancer overtook solid cancer as the main type of neoplasm in patients for whom malignancy was the primary indication for the use of the PSI. The actuarial incidence of PSI withdrawal owing to adverse effects did not change significantly over time.

Steroid use in heart transplant patients in Spain in the current era: a multicenter survey.

OBJECTIVE: Steroid withdrawal (SW) from maintenance therapy in heart transplant patients is still a controversial subject. We designed a questionnaire to ascertain the attitudes and procedures of a number of Spanish heart transplant units (16) regarding the use/withdrawal of steroids as part of the immunosuppressive maintenance therapy. MATERIALS AND METHODS: We sent an 11-item questionnaire to the clinical director in charge of each unit. The questionnaire was completed and returned by 14 units. RESULTS: In 21.5% of the centers SW was performed in all patients, while 78.5% of the centers only performed SW in selected patients. In 57% of units SW was performed at 12 months posttransplantation and between 6 and 12 months in the rest. Fewer than 20% of patients were steroid-free in 46% of units while in 23% of units this proportion was >50%. In 11 units, the minimum prednisone dose administered was

Malignancy after heart transplantation: incidence, prognosis and risk factors.

The Spanish Post-Heart-Transplant Tumour Registry comprises data on neoplasia following heart transplantation (HT) for all Spanish HT patients (1984-2003). This retrospective analysis of 3393 patients investigated the incidence and prognosis of neoplasia, and the influence of antiviral prophylaxis. About 50% of post-HT neoplasias were cutaneous, and 10% lymphomas. The cumulative incidence of skin cancers and other nonlymphoma cancers increased with age at HT and with time post-HT (from respectively 5.2 and 8.9 per 1000 person-years in the first year to 14.8 and 12.6 after 10 years), and was greater among men than women. None of these trends held for lymphomas. Induction therapy other than with IL2R-blockers generally increased the risk of neoplasia except when acyclovir was administered prophylactically during the first 3 months post-HT; prophylactic acyclovir halved the risk of lymphoma, regardless of other therapies. Institution of MMF during the first 3 months post-HT reduced the incidence of skin cancer independently of the effects of sex, age group, pre-HT smoking, use of tacrolimus in the first 3 months, induction treatment and antiviral treatment. Five-year survival rates after first tumor diagnosis were 74% for skin cancer, 20% for lymphoma and 32% for other tumors.

An integrated approach to the quantification of aortic regurgitation by Doppler echocardiography.

BACKGROUND: Although different Doppler methods have been proposed for the quantification of aortic regurgitation, no study has prospectively compared these methods with each other and their correlation with angiography. The aim of this study was to prospectively analyze the usefulness of different Doppler echocardiography parameters by testing all such parameters in each patient. METHODS: Fifty-one patients with aortic regurgitation underwent 2-dimensional and Doppler echocardiographic studies and catheterization. The following Doppler indexes were analyzed and compared with aortography. Color Doppler: (1) jet color height/left ventricular outflow tract height in parasternal long-axis view, and (2) jet color area/left ventricular outflow tract area in short-axis view. Continuous Doppler: (3) regurgitant flow pressure half-time, (4) regurgitant flow time velocity integral (in centimeters), and (5) regurgitant flow time velocity integral (in centimeters)/diastolic period (in milliseconds). Pulsed Doppler in thoracic and abdominal aorta: (6) time velocity integral of diastolic reverse flow (in centimeters), (7) time velocity integral of systolic anterograde flow/integral of diastolic reverse flow, (8) (time velocity integral of diastolic reverse flow/diastolic period) x 100, and (9) diastolic reverse flow duration/diastolic period (as a percentage). We compared these parameters with severity of regurgitation measured by angiography and classified as mild, moderate, or severe. RESULTS: The most useful parameters were (1) jet color height/left ventricular outflow tract height (correctly classified 42 of 49 patients), (2) (time velocity integral of diastolic reverse flow/diastolic period) x 100 in the thoracic aorta (correctly classified 41 of 46 patients), and (3) (time velocity integral of diastolic reverse flow/diastolic period) x 100 in the abdominal aorta (correctly classified 42 of 49 patients). Sequential integration of these 3 parameters correctly classified 96% of patients (44 of 46 patients) and was achieved in 90% of cases. CONCLUSION: An integrated combination of several Doppler parameters can quickly and accurately classify the degree of aortic regurgitation as determined by angiography.

Quantitative three-dimensional reconstruction of left ventricular volume with complete borders detected by acoustic quantification underestimates volume.

Recently a new acoustic-quantification (AQ) technique has been developed to provide on-line automated border detection with an integrated backscatter analysis. Prior studies have largely correlated AQ areas with volumes without direct comparison of volumes for agreement. By using complete AQ-detected borders as the input to a validated method for three-dimensional echocardiographic (3DE) reconstruction, we can compare an entire cavity volume measured with the aid of AQ against a directly measured volume. This would also explore the possibility of applying AQ to 3DE reconstruction to reduce tracing time and enhance routine applicability. To compare reconstructed volumes with actual values in a stable standard allowing direct volume measurement, the left ventricles of 13 excised animal hearts were studied with a 3DE system that automatically combines two-dimensional (2D) images and their locations. Intersecting 2D views were obtained with conventional scanning and AQ imaging, with gains optimized to permit 3D reconstruction by detecting the most continuous AQ borders for each view, with maximal cavity size. Reconstruction was performed with manually traced central endocardial reflections and AQ-detected borders visually reproduced the left ventricular shapes; the AQ reconstructions, however, were consistently smaller. The reconstructed left ventricular (LV) volumes correlated well with actual values by both manual and AQ techniques (r = 0.93 and 0.88, with standard errors of 2.3 cc and 2.0 cc, p = not significant [NS]). Agreement with actual values was relatively close for the manually traced borders (y = 0.93x + 0.68, mean difference = -0.8 +/-2.2 cc). AQ-derived reconstructions consistently underestimated LV volume by 39 +/- 10% (y = 0.62x-0.09, mean difference = -7.8 +/- 3.0 cc, different from manually traced and actual volumes by analysis of variance [ANOVA], F = 69, p<0.00001). The AQ-detected threshold signal was displaced into the cavity, and volume between walls and false tendons was excluded, leading to underestimation, which increased with increasing cavity volume (r = 0.76). The AQ technique can therefore be applied to 3DE reconstruction, providing volumes that correlate well with directly measured values in a stable in vitro standard, minimizing observer decisions regarding manual border placement after image acquisition. However, when the complete borders needed for 3D reconstruction are used, absolute volumes are underestimated with current algorithms that integrate backscatter and displace the detected threshold into the ventricular cavity.

Intracardiac echocardiography: in vitro and in vivo validation for right ventricular volume and function.

To determine the feasibility and accuracy of intracardiac ultrasonography (ICUS) for the measurement of right ventricular (RV) volumes and function, a 10 MHz ICUS catheter was used in an in vitro and in vivo model. In the in vitro study, 16 sheep hearts were imaged. Sequential cross-sectional images from RV apex to base were recorded during a calibrated pullback. Volumes were calculated by applying Simpson's algorithm. ICUS-obtained volumes correlated well with actual volumes (standard error of estimate [SEE] = 2.3 ml, r = 0.98). For the in vivo study, a beating-heart canine model was used (31 hemodynamic stages in six dogs). Actual volumes were measured by an intracavitary balloon connected to an external column. Sequential cross-sectional images were recorded during the ICUS catheter pullback from apex to base of the RV, and volumes calculated by Simpson's algorithm. Good correlations were observed between ICUS and actual values for diastolic (SEE = 4.1 ml, r = 0.97), systolic (SEE = 3.4 ml, r = 0.96), and ejection fraction (SEE = 3.1%, r = 0.87) values. This new technique can accurately quantitate RV volumes, can function both in vitro and in vivo, and has the potential for increasing applications to questions of clinical and research interest.

New method for accurate calculation of regurgitant flow rate based on analysis of Doppler color flow maps of the proximal flow field. Validation in a canine model of mitral regurgitation with initial application in patients.

OBJECTIVES: The purpose of this study was to develop a rational and objective method for selecting a region in the proximal flow field where the hemispheric formula for calculating regurgitant flow rates by the flow convergence technique is most accurate. BACKGROUND: A major obstacle to clinical implementation of the proximal flow convergence method is that it assumes hemispheric isovelocity contours throughout the Doppler color flow map, whereas contour shape depends critically on location in the flow field. METHODS: Twenty mitral regurgitant flow rate stages were produced in six dogs by implanting grommet orifices into the anterior mitral leaflet and varying driving pressures so that actual peak flow rate could be determined from the known effective regurgitant orifice times the orifice velocity. Because plotting flow rate calculated by using a hemispheric formula versus alias velocities produces underestimation near the orifice and overestimation far from it, this plot was fitted to a polynomial function to allow identification of an inflection point within a relatively flat intermediate zone, where factors causing overestimation and underestimation are expected to be unimportant or balanced. The accuracy of flow rate calculation by the inflection point was compared with unselective and selective averaging techniques. Clinical relevance, initial feasibility and correlation with an independent measure were tested in 13 consecutive patients with mitral regurgitation who underwent cardiac catheterization. RESULTS: 1) The accuracy of single-point calculations was improved by selecting points in the flat portion of the curve (y = 1.15x - 3.34, r = 0.87, SEE = 22.1 ml/s vs. y = 1.34x - 1.99, r = 0.71, SEE = 45.6 ml/s, p < 0.01). 2) Selective averaging of points in the flat portion of the curve further improved accuracy and decreased scatter compared with unselective averaging (y = 1.08x + 4.8, r = 0.96, SEE = 11.6 ml/s vs. y = 1.30x + 0.6, r = 0.90, SEE = 20.9 ml/s, p < 0.01). 3) The proposed algorithm for mathematically identifying the inflection point provided the best results (y = 0.96x + 4.5, r = 0.96, SEE = 9.9 ml/s), with a mean error of 1.6 +/- 9.7 ml/s vs. 11.4 +/- 11.7 ml/s for selective averaging (p < 0.01). In patients, the proposed algorithm identified an inflection point at which calculated regurgitant volume agreed best with invasive measurements (y = 1.1x - 0.61, r = 0.93, SEE = 17 ml). CONCLUSIONS: The accuracy of the proximal flow convergence method can be significantly improved by analyzing the flow field mathematically to identify the optimal isovelocity zone before using the hemispheric formula to calculate regurgitant flow rates. Because the proposed algorithm is objective, operator independent and, thus, suitable for automatization, it could provide the clinician with a powerful quantitative tool to assess valvular regurgitation.

Intracardiac ultrasonographic assessment of atrial septal defect area: in vitro validation and technical considerations.

Assessment of atrial septal defect (ASD) size and shape is important for planning and guiding its transcatheter occlusion and can potentially be achieved by intracardiac ultrasonography (ICUS). ICUS accuracy, however, must first be established against stable standards and technical imaging requirements defined. We therefore used 10, 20, and 30 MHz ICUS catheters to examine 17 ASDs that were 0.16 to 6.7 cm2 in area and were surgically created in excised ovine hearts with 10, 20, and 30 MHz ICUS catheters. ASD shape and area by ICUS were compared with direct video images of the actual ASD. In all instances minimal area by ICUS pullback agreed well with actual values (y = 1.04x + 0.2, SEE = 0.23 cm2, r = 0.99) and corresponded well with defect shapes. The maximum angle between ultrasonography beam and septal plane allowing for complete ASD visualization was 20 degrees. The angle depended on transducer frequency and septal thickness. This new technique has potential value for the accurate assessment of ASD shape and size and may be especially useful in the setting of transcatheter occlusion.

Quantitative three-dimensional reconstruction of aneurysmal left ventricles. In vitro and in vivo validation.

BACKGROUND: Current two-dimensional (2D) echocardiographic measures of left ventricular (LV) volume are most limited by aneurysmal distortion, which restricts application of simple geometric models that assume symmetrical shape. 2D methods also fail to provide separate volumes of the aneurysm and nonaneurysmal residual LV cavity, which could help assess the stroke volume wasted by dyskinesis and the potential residual LV body to guide surgical approaches and predict their outcome. Three-dimensional (3D) echocardiographic reconstruction has potential advantages for assessing aneurysmal left ventricles because it is not dependent on geometric assumptions, does not require standardized views that may exclude portions of the aneurysm, and can potentially measure separate aneurysm and nonaneurysm cavity volumes of any shape. The purpose of this study was first, to validate the accuracy of 3D echocardiographic reconstruction for quantifying total LV and separate LV body and aneurysm volumes in vitro so as to provide direct standards for the separate volumes; and second, to determine the feasibility and accuracy of 3D echocardiographic reconstruction for quantifying the total volume and function of aneurysmal left ventricles in an animal model, providing a reference standard for instantaneous LV volume. METHODS AND RESULTS: A recently developed 3D system that automatically combines 2D images and their locations was applied (1) to reconstruct 10 aneurysmal ventricular phantoms and 12 gel-filled autopsied human hearts with aneurysms, comparing cavity volumes (total and aneurysm) to those measured by fluid displacement; and (2) to reconstruct the left ventricle during 19 hemodynamic stages in four dogs with surgically created LV aneurysms, comparing total volumes with actual instantaneous values measured by an intracavitary balloon attached to an external column for validation and also calculating the stroke volume wasted by aneurysmal dyskinesis. 3D reconstruction reproduced the distorted aneurysmal LV shapes. In vitro, calculated volumes (aneurysm, nonaneurysm, and total) agreed well with actual values, with correlation coefficients of .99 and SEEs of 3.2 to 6.1 cm3 for phantoms and 3.4 to 4.2 cm3 for autopsied hearts (mean error, < 4% for both). In vivo, LV end-diastolic, end-systolic, and stroke volumes as well as ejection fraction calculated by 3D echocardiography correlated well with actual values (r = .99, .99, .95, and .99, respectively) and agreed closely with them (SEE = 4.3 cm3, 3.5 cm3, 1.7 cm3, and 2%, respectively). The stroke volumes wasted by the aneurysm were -20.1 +/- 19.3% of LV body (nonaneurysm) stroke volume. CONCLUSIONS: Despite distorted ventricular shapes, a recently developed 3D echocardiographic system and surfacing algorithm can accurately reconstruct aneurysmal left ventricles and quantify total LV volume (validated in vivo and in vitro) as well as the separate volumes of the aneurysm and residual LV body (validated in vitro). This should improve our ability to evaluate such ventricles and guide surgical approaches.

[A critical review of the role of endomyocardial biopsy in heart transplantation]. / Revisión crítica del papel de la biopsia endomiocárdica en el trasplante cardíaco.

Endomyocardial biopsy is still considered the most reliable means for the detection of acute cardiac rejection after heart transplantation. However, this technique has several limitations that might not have been sufficiently underscored. In this review, some of the limitations of endomyocardial biopsy are discussed. In order to overcome these problems, the possibility of using this technique in a more selective and oriented manner is suggested. A combined approach is proposed, using serial echocardiographic studies to monitor rejection episodes and to selectively indicate the need for endomyocardial biopsy. In this way, the total number of biopsies might be reduced along with a more individualized therapy for the rejection episodes. The experience with this new approach in the Heart Transplantation Program of the Hospital Universitario Marqués de Valdecilla, Santander, Spain, is presented.

Intracardiac ultrasound measurement of volumes and ejection fraction in normal, infarcted, and aneurysmal left ventricles using a 10-MHz ultrasound catheter.

BACKGROUND: Our objective was to examine the accuracy of intracardiac ultrasound (ICUS) measurement of left ventricular (LV) volumes and ejection fraction (EF) using a 10-MHz ultrasound catheter. ICUS can image the LV in cross sections at all levels along the long axis with a transducer mounted on the tip of a catheter. Sequential serial LV cross-sectional images can be obtained during cardiac catheterization and used to calculate LV volumes by Simpson's rule. This technique may be an alternative to contrast LV angiography. METHODS AND RESULTS: A beating-heart in vivo model was created to measure LV volume directly and continuously with an intracavity high-compliance latex balloon connected to a calibrated extracardiac reservoir in eight dogs in 35 experimental stages. A 10F ICUS catheter with a 10-MHz single-element transducer was introduced retrogradely via the aortic valve to the apex. Series of sequential LV cross-sectional images were recorded from the apex to the base during a calibrated pullback of the catheter. At each 5-mm interval, the LV cross section was traced at end diastole and end systole. LV volume was calculated by Simpson's rule by integrating all segmental areas multiplied by segmental height. The effect on accuracy of selecting 5-, 10-, or 15-mm heights or a single section at the midventricular level for measurement was assessed. The influence of distorted ventricular shape on the accuracy of ICUS measurements of LV volume was evaluated. This method was applied in 19 experimental stages in 10 intact dogs and pigs catheterized via the femoral artery. In the in vivo canine model, LV end-diastolic volume, end-systolic volume, and EF determined by ICUS using 5-, 10-, or 15-mm segments were not different from the actual measurements. But correlation and agreement between ICUS end-diastolic volume and direct measurements for 5- and 10-mm segments were significantly better than for 15-mm segments or a single section. Similar excellent correlations and agreement were observed for actual and ICUS-derived end-systolic volumes using 5-, 10-, or 15-mm segments. The ICUS-derived EF correlated very well with actual EF with a small measurement error of 3.91 +/- 2.59% for 5-mm or 4.13 +/- 2.79% for 10-mm segments but a significantly greater measurement error for 15-mm segments (5.35 +/- 3.76%) or single sections (14.8 +/- 12.2%). The presence of LV infarction or aneurysm did not significantly influence the accuracy of ICUS calculations for segmental heights < or = 10 mm. Application in intact animals demonstrated a good correlation between stroke volume measured by ICUS and by thermodilution or flowmeter. ICUS-derived LV volumes correlated well with biplane angiographic volumes, with a tendency toward underestimation. There was no significant difference between ICUS-determined LV EF and EF determined by angiography. CONCLUSIONS: Intracardiac echocardiography accurately measures LV volumes and global systolic function in both regularly shaped and distorted left ventricles. This technique directly and continuously visualizes circumferential LV endocardium and wall thickness without contrast agents or geometric assumptions for calculation of LV volume. Thus, it should be particularly useful in patients at high risk for contrast-related complications or distorted LV shapes in which geometric assumptions may not be valid.

Determinants of functional tricuspid regurgitation in incomplete tricuspid valve closure: Doppler color flow study of 109 patients.

OBJECTIVES: The aim of this study was to investigate the association between the pattern of incomplete tricuspid valve closure and the presence of tricuspid regurgitation and to identify factors that determine the severity of regurgitation associated with this pattern. BACKGROUND: The incomplete tricuspid valve closure pattern (defined as apical displacement of the leaflets) has been described by two-dimensional echocardiography. However, whether this pattern is universally associated with tricuspid regurgitation and the determinants of severity of regurgitation in its presence have not been studied by Doppler color flow mapping. METHODS: We identified 109 consecutive patients (mean age 62 +/- 17 years) with incomplete tricuspid valve closure who were studied by Doppler color flow mapping. We measured the linear apical displacement of the coaptation point from the tricuspid annulus and the area of displacement between the leaflets and annulus. Right atrial, ventricular and annular dimensions were measured and compared with those in a group of normal subjects. RESULTS: Tricuspid regurgitation was present in all patients with the incomplete closure pattern; it was mild in 14%, moderate in 19% and severe in 67%. Apical displacement was significantly greater (p < 0.02) in those with severe regurgitation than in those with mild regurgitation or in normal subjects. Tricuspid annulus dilation was the only independent predictor of severity of regurgitation. The right ventricle was not significantly dilated in 32% of patients, and right ventricular systolic pressure was not correlated with the severity of regurgitation and was < 30 mm Hg in 11% of patients. CONCLUSIONS: Tricuspid regurgitation was associated with incomplete tricuspid valve closure in all patients studied and was moderate to severe in 86%. Impaired coaptation is best reflected by the displacement area between the leaflets and the annulus. High pulmonary pressure and significant right ventricular dilation are not prerequisites for functional tricuspid regurgitation. Annular dilation is the most consistent and important determinant of this lesion.

Quantification of pericardial effusions by three-dimensional echocardiography.

OBJECTIVES: The purpose of this study was to examine the accuracy of three-dimensional echocardiography for the quantification of asymmetric pericardial effusion volume and to compare this new technique with two-dimensional echocardiography. BACKGROUND: Quantification of pericardial effusion by two-dimensional echocardiography relies on a symmetric distribution of the fluid. Three-dimensional echocardiography can quantitate volume without these limitations, but its accuracy for pericardial effusion volume has not yet been assessed. METHODS: In six open chest dogs, 41 different asymmetrically distributed pericardial effusions of known volume were created by serial infusions of fluid through a pericardial catheter. The hearts were imaged using an automated echocardiographic method that integrates three-dimensional spatial and imaging data. The surfaces of the pericardial sac and heart were then reconstructed, and the volumes of pericardial effusions were calculated. Two-dimensional echocardiography was performed simultaneously, and volumes were calculated using the prolate ellipsoid method. Asymmetric distribution of the fluid was obtained by applying localized hydrostatic pressure to the pericardium. RESULTS: The volumes of pericardial effusion quantified using three-dimensional echocardiography correlated well with actual volumes (y = 1.0x - 1.4, SEE = 7.7 ml, r = 0.98). Two-dimensional echocardiography had an acceptable correlation (y = 1.0x + 2.3, SEE = 23 ml, r = 0.84), but a marked degree of variation from the true value was observed for any individual measurement. CONCLUSIONS: Three-dimensional echocardiography accurately quantifies pericardial effusion volume in vivo, even when the fluid is distributed asymmetrically, whereas two-dimensional echocardiography is less reliable. This new technique may be of clinical value in quantitating pericardial effusion, especially in the serial evaluation of asymmetric or loculated effusions.

[The estimation of the severity of tricuspid insufficiency by Doppler color: the effects of gain, pulse repetition frequency and the echographic view]. / Estimación de la severidad de la insuficiencia tricúspide por Doppler color: efectos de la ganancia, frecuencia de repetición de pulsos y plano ecocardiográfico.

INTRODUCTION AND OBJECTIVES: Regurgitant jet area is to date the most widely accepted color Doppler parameter for quantitation of atrium-ventricular regurgitations. In experimental studies, it has been demonstrated that color regurgitant jet area is greatly influenced by technical settings. The present study was aimed to analyze the effect of gain setting, pulse repetition frequency and echocardiographic plane on color jet area in patients with tricuspid regurgitation. METHODS: We studied 64 patients with nontrivial (more than 1 cm2), rheumatic tricuspid regurgitation. Examinations were performed in apical four-chamber and right ventricle inflow-tract views, at two gain settings (subsaturation gain and 1/3 reduced gain) and at two pulse repetition frequencies (3.1 and 3.8 kHz). Therefore, every regurgitant jet was study under 8 different technical conditions. The remaining technical settings were held unchanged included throughout the studies. The traced area induced central varianced and aliased signals, as well as the immediately contiguous nonturbulent velocities that were moving in the same direction as the jet. Measurements were taken from 5 and 3 representative cycles in patients with atrial fibrillation and sinus rythm, respectively. RESULTS: Globally, reduction in gain setting produced a color area decrease by 50%. This reduction was of greater extent for small jets (less than 5 cm2, 45 +/- 17%) with respect to larger jets (more than 5 cm2, 61 +/- 30%, p = 0.0009). Results were similar for both apical four-chamber and right ventricle inflow views and for the two pulse repetition frequencies. At a given color gain level and echocardiographic view, pulse repetition frequency at 3.1 kHz produced greater color areas (by 3-11%) than frequency at 3.8 kHz, but the difference was not significant. Overall, color jet area was significantly greater in right ventricle inflow view than in apical four-chamber view, but substantial individual variability was observed. Difference between both views was greater than 40% in 28% of patients, with the largest color area in right ventricle inflow view in most, especially in those patients with eccentric jets. CONCLUSIONS: Gain setting and echocardiographic view greatly affect regurgitant jet area by color Doppler in patients with tricuspid regurgitation. Therefore, standardization of technical settings is mandatory in order to avoid diagnostic pitfalls.

Three-dimensional echocardiography: in vivo validation for right ventricular free wall mass as an index of hypertrophy.

OBJECTIVES: This study tested the ability of three-dimensional echocardiography to reconstruct the right ventricular free wall and determine its mass in vivo using a system that automatically combines two-dimensional images with their spatial locations. BACKGROUND: Right ventricular free wall thickness is limited as an index of right ventricular hypertrophy because right ventricular mass may increase by dilation without increased thickness and because trabeculations and oblique views can exaggerate thickness in individual M-mode and two-dimensional scans. Three-dimensional echocardiography may have potential advantages because it can integrate the entire free wall mass, uninfluenced by oblique views or geometric assumptions. METHODS: The three-dimensional system was applied to 12 beating canine hearts to reconstruct the right ventricular free wall in intersecting views. The corresponding mass was compared with actual weights of the excised right ventricular free wall (15.5 to 78 g). For comparison, right ventricular sinus and outflow tract thickness were also measured by two-dimensional echocardiography, and the ability to predict mass from these values was determined. RESULTS: The three-dimensional algorithm successfully reproduced right ventricular free wall mass, which agreed well with actual values: y = 1.04x + 0.02, r = 0.985, SEE = 2.7 g (5.7% of the mean value). The two-dimensional predictions showed increased scatter: The variance of mass estimation, based on thickness, was 9.5 to 12.5 (average 11) times higher than the three-dimensional method (p < 0.02). CONCLUSIONS: Despite the irregular crescentic shape of the right ventricle, its free wall mass can be accurately measured by three-dimensional echocardiography in vivo, providing closer agreement with actual mass than predictions based on wall thickness. This method, with the increased efficiency of the three-dimensional system, can potentially improve our ability to evaluate the presence and progression of right ventricular hypertrophy.