Highly effective cystic fibrosis transmembrane conductance (regulator) modulator therapy: shifting the curve for most while leaving some further behind.

PURPOSE OF REVIEW: Traditional cystic fibrosis (CF) care had been focused on early intervention and symptom mitigation. With the advent of highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy (HEMT), in particular, the approval of elexacaftor/tezacaftor/ivacaftor in 2019, there has been a dramatic improvement in outcomes in CF. The purpose of this article is to review the benefits, limitations, and impact of HEMT as well as discuss the new implications, challenges, and hope that modulators bring to people with CF (pwCF). RECENT FINDINGS: HEMT has demonstrated sustained improvement in lung function, nutrition, quality of life, and survival for over 90% of pwCF. As HEMT has delivered such promise, there is a small but significant portion of pwCF who do not benefit from HEMT due to ineligible mutations, intolerance, or lack of accessibility to modulators. SUMMARY: HEMT has significantly improved outcomes, but continued research is needed to understand the new challenges and implications the era of HEMT will bring, as well as how to provide equitable care to those who are unable to benefit from HEMT.

Engineering of hyaline cartilage with a calcified zone using bone marrow stromal cells.

OBJECTIVE: In healthy joints, a zone of calcified cartilage (ZCC) provides the mechanical integration between articular cartilage and subchondral bone. Recapitulation of this architectural feature should serve to resist the constant shear force from the movement of the joint and prevent the delamination of tissue-engineered cartilage. Previous approaches to create the ZCC at the cartilage-substrate interface have relied on strategic use of exogenous scaffolds and adhesives, which are susceptible to failure by degradation and wear. In contrast, we report a successful scaffold-free engineering of ZCC to integrate tissue-engineered cartilage and a porous biodegradable bone substitute, using sheep bone marrow stromal cells (BMSCs) as the cell source for both cartilaginous zones. DESIGN: BMSCs were predifferentiated to chondrocytes, harvested and then grown on a porous calcium polyphosphate substrate in the presence of triiodothyronine (T3). T3 was withdrawn, and additional predifferentiated chondrocytes were placed on top of the construct and grown for 21 days. RESULTS: This protocol yielded two distinct zones: hyaline cartilage that accumulated proteoglycans and collagen type II, and calcified cartilage adjacent to the substrate that additionally accumulated mineral and collagen type X. Constructs with the calcified interface had comparable compressive strength to native sheep osteochondral tissue and higher interfacial shear strength compared to control without a calcified zone. CONCLUSION: This protocol improves on the existing scaffold-free approaches to cartilage tissue engineering by incorporating a calcified zone. Since this protocol employs no xenogeneic material, it will be appropriate for use in preclinical large-animal studies.

Critical components of the pluripotency network are targets for the p300/CBP interacting protein (p/CIP) in embryonic stem cells.

p/CIP, also known as steroid receptor coactivator 3 (SRC-3)/Nuclear Receptor Coactivator 3 (NCoA3), is a transcriptional coactivator that binds liganded nuclear hormone receptors, as well as other transcription factors, and facilitates transcription through direct recruitment of accessory factors. We have found that p/CIP is highly expressed in undifferentiated mouse embryonic stem cells (mESCs) and is downregulated during differentiation. siRNA-mediated knockdown of p/CIP decreased transcript levels of Nanog, but not Oct4 or Sox2. Microarray expression analysis showed that Klf4, Tbx3, and Dax-1 are significantly downregulated in mESCs when p/CIP is knocked down. Subsequent chromatin immunoprecipitation (ChIP) analysis demonstrated that Tbx3, Klf4, and Dax-1 are direct transcriptional targets of p/CIP. Using the piggyBac transposition system, a mouse ESC line that expresses Flag-p/CIP in a doxycycline-dependent manner was generated. p/CIP overexpression increased the level of target genes and promoted the formation of undifferentiated colonies. Collectively, these results indicate that p/CIP contributes to the maintenance of ESC pluripotency through direct regulation of essential pluripotency genes. To better understand the mechanism by which p/CIP functions in ESC pluripotency, we integrated our ChIP and transcriptome data with published protein-protein interaction and promoter occupancy data to draft a p/CIP gene regulatory network. The p/CIP gene regulatory network identifies various feed-forward modules including one in which p/CIP activates members of the extended pluripotency network, demonstrating that p/CIP is a component of this extended network.

Stress reactivity of emotional and verbal speech content in schizophrenia.

Speech fundamental frequencies (SFFs) are nonverbal sound frequencies that convey emotion in speech. The degree of SFF long-term averaged spectra (LTAS) convergence between conversants reflects aspects of conversant-reported quality of the interaction (e.g., emotional synchrony). This study investigated whether SFF LTAS convergence between inpatients diagnosed with schizophrenia (n = 20) and an interviewer was associated with severity of illness (SOI), formal speech disturbance (FSD), and stress reactivity of FSD. Participants provided speech samples describing stressful and nonstressful life experiences. In the stress condition, SFF LTAS was negatively correlated with SOI and FSD. Moreover, patients exhibiting stress reactivity of FSD also evidenced stress reactivity of SFF LTAS. These findings suggest that the emotional and verbal contents of speech are disrupted by stress in schizophrenia, and SOI is associated with FSD and reduced emotional communication during stressful conditions. The interaction between stress reactivity of FSD and SFF LTAS supports the construct validity of a reactivity dimension in schizophrenia.

Altered proliferative response by T lymphocytes of Ly-6A (Sca-1) null mice.

Ly-6A is a murine antigen which is implicated in lymphocyte activation and may be involved in activation of hematopoietic stem cells. Antibody cross-linking studies and antisense experiments have suggested that Ly-6A is a lymphocyte coactivation molecule. To better understand the function of Ly-6A, we used gene targeting to produce Ly-6A null mice which are healthy and have normal numbers and percentages of hematopoietic lineages. However, T lymphocytes from Ly-6A-deficient animals proliferate at a significantly higher rate in response to antigens and mitogens than wild-type littermates. In addition, Ly-6A mutant splenocytes generate more cytotoxic T lymphocytes compared to wild-type splenocytes when cocultured with alloantigen. This enhanced proliferation is not due to alterations in kinetics of response, sensitivity to stimulant concentration, or cytokine production by the T cell population, and is manifest in both in vivo and in vitro T cell responses. Moreover, T cells from Ly-6A-deficient animals exhibit a prolonged proliferative response to antigen stimulation, thereby suggesting that Ly-6A acts to downmodulate lymphocyte responses.

Function of PI3Kgamma in thymocyte development, T cell activation, and neutrophil migration.

Phosphoinositide 3-kinases (PI3Ks) regulate fundamental cellular responses such as proliferation, apoptosis, cell motility, and adhesion. Viable gene-targeted mice lacking the p110 catalytic subunit of PI3Kgamma were generated. We show that PI3Kgamma controls thymocyte survival and activation of mature T cells but has no role in the development or function of B cells. PI3Kgamma-deficient neutrophils exhibited severe defects in migration and respiratory burst in response to heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPCR) agonists and chemotactic agents. PI3Kgamma links GPCR stimulation to the formation of phosphatidylinositol 3,4,5-triphosphate and the activation of protein kinase B, ribosomal protein S6 kinase, and extracellular signal-regulated kinases 1 and 2. Thus, PI3Kgamma regulates thymocyte development, T cell activation, neutrophil migration, and the oxidative burst.

Targeted high and low speech frequency bands to right and left ears respectively improve task performance and perceived sociability in dyadic conversations.

Past research shows that the lower nonverbal frequencies of the human voice, beneath .5 kHz, transmit an acoustic signal promoting social convergence and status accommodation between human interlocutors. We conducted a laboratory experiment and a validation study to explore the possible communications benefits of targeting the low-frequency band to the left ears of human participants and the high-frequency band to the right ears. We compare this "Enhanced" condition with two other conditions: a "Confounded" condition, in which the low-frequency band was targeted to participants' right ears and the higher-frequency band to their left ears; and a Control condition, in which the entire unaltered frequency band was targeted to both ears. For the duration of their interaction, experiment participants engaged in dyadic conversations while attempting to complete a task via an audio-visual communication system. Our results show that both the speed and accuracy of task completion were significantly improved in the Enhanced condition. In the second validation study, groups of participants rated the quality of videotaped conversations from the experiment using a semantic differential instrument. The Enhanced condition conversations were rated significantly more affectively favourable than either the unaltered Control or Confounded condition conversations. Overall, our results exhibit potential for enhancing two-way electronic communications and improving task performances in media environments.

Effects of dichotically enhanced electronic communication on crash risk and performance during simulated driving.

In a driving simulator experiment, male and female college students received turn-by-turn driving directions and cognitive tasks while interacting with an experimenter via an audio communication system. In an Enhanced condition (n = 29), lower speech frequencies (containing the speech fundamental frequency) were routed to participants' left ears (with right cerebral-hemisphere processing) and verbal frequencies above the speech fundamental frequency were routed to right ears (with left hemisphere processing). A control group (n = 31) heard unfiltered communications in both ears. Compared to those in the Control condition, participants in the Enhanced condition were significantly less likely to crash and had nonsignificantly lower rates of driving errors (speed infractions, improper lane position, and following distance errors). The results suggest a means of alleviating cognitive load pressure and mitigating crash risk when complex equipment is operated concurrently with two-way electronic communications (cell phone communication while driving, air-to-air and air-to-ground communications, etc.).

Evaluating dose-limiting toxicities of MDM2 inhibitors in patients with solid organ and hematologic malignancies: A systematic review of the literature.

INTRODUCTION: Mouse double minute 2 protein (MDM2), a negative regulator of the p53 tumour suppressor gene, is frequently amplified in malignancies. MDM2 antagonists have shown efficacy in treating malignancies with MDM2 overexpression and can overcome chemoresistance in acute myeloid leukemia. We systematically evaluated the safety profile of MDM2 inhibitors in the treatment of solid organ and hematologic malignancies. MATERIALS AND METHODS: We searched Medline and EMBASE from January 1947 to November 2018 for prospective clinical studies, in English or French, investigating any MDM2 inhibitor in pediatric or adult cancers, and reporting dose and toxicity outcomes. Primary outcome was dose-limiting toxicity (DLT) and secondary outcome was death. RESULTS: The search yielded 493 non-duplicate citations. Eighteen studies of 10 inhibitors met inclusion criteria (total N = 1005 patients). Two-thirds of included studies did not define DLTs and the reporting of toxicities was highly variable. The most commonly reported DLTs were cytopenias, gastrointestinal toxicity, metabolic disturbances, fatigue and cardiovascular toxicity; there was one death attributed to treatment toxicity. CONCLUSION: MDM2 antagonists have been studied in a variety of malignancies with toxicities similar to other commonly used chemotherapy agents and may represent a safe adjuvant treatment for further study in in acute leukemia.

Cloning and developmental expression analysis of the murine c-mer tyrosine kinase.

We have cloned the putative mouse homologue of the human c-mer receptor tyrosine kinase proto-oncogene. Comparison of the mouse and human c-mer amino acid sequences reveals an overall identity of 88%. Similar to the human, the extracellular region of the murine c-mer protein possesses two amino terminal immunoglobulin-like domains and two membrane proximal fibronectin type III domains, which places it in the Axl family of tyrosine kinases. Our analysis of the Axl family identifies eight different regions of amino acid consensus that have residues characteristic of this and no other tyrosine kinase family; six of the eight are within tyrosine kinase subdomains. The homology within the Axl family is highest between c-mer and c-eyk, the chicken proto-oncogene of the tumor virus gene product v-eyk. Northern analysis of adult tissues suggests that the mouse c-mer, although expressed in many tissues, has an expression pattern unique among Axl family members. In normal adult hematopoietic cells c-mer seems to be expressed predominantly if not exclusively in the monocytic lineage. Mouse c-mer is expressed during most, if not all, stages of embryological development beginning in the morula and blastocyst and progressing through the yolk sac and fetal liver stages. This early and consistent expression of c-mer was confirmed during in vitro differentiation of embryonic stem cells. The embryonic expression profile of c-mer suggests that this tyrosine kinase may play an important function in the developing mouse.

Accurate preoperative diagnosis of pericardial constriction using cine computed tomography.

OBJECTIVES: The purpose of this study was to determine the accuracy of cine computed tomography in the diagnosis of constrictive pericarditis. BACKGROUND: Constrictive pericarditis is characterized by abnormalities of both cardiac structure and function. Accurate diagnosis requires detection of both a thickened pericardium and abnormal ventricular diastolic filling. At present, no one diagnostic technique has demonstrated sufficient accuracy in this setting. Cine computed tomography is a relatively new cardiac imaging mode with very high time and spatial resolution that has the potential to accurately diagnose constrictive pericarditis. METHODS: Twelve consecutive patients were retrospectively identified who had catheterization findings suggestive of constrictive physiology, had undergone a cine computed tomographic examination and had pathologic data that delineated the status of the pericardium. Group 1 (with constrictive pericarditis; n = 5) had surgical confirmation of thickened pericardium and improved clinically after pericardiectomy. Group 2 (no constrictive pericarditis; n = 7) had cardiomyopathy with normal pericardium. Seven normal volunteers (Group 3) were also studied. Cine computed tomograms were obtained for the entire heart (8-mm slices, 17 frames/s, nonionic contrast medium). Pericardial thickness was measured at 10 degrees intervals at three ventricular levels in each subject. The rapidity of diastolic filling was assessed by calculating the percent filling fraction in early diastole. RESULTS: Pericardial thickness was 10 +/- 2 mm (mean +/- SD) in Group 1, 2 +/- 1 mm in Group 2 and 1 +/- 1 mm in Group 3 (p < 0.05, constrictive pericarditis vs. no constrictive pericarditis). Left ventricular filling fraction was 83 +/- 6% in Group 1, 62 +/- 9% in Group 2 and 44 +/- 5% in Group 3. Right ventricular filling fraction was 93 +/- 5% in Group 1, 62 +/- 14% in Group 2 and 35 +/- 6% in Group 3 (p < 0.05, Group 1 vs. Groups 2 and 3). Both indexes provided a clear-cut distinction between patients with and without constriction. CONCLUSIONS: Cine computed tomography simultaneously provides both anatomic and physiologic data that allow accurate preoperative diagnosis of pericardial constriction.

Patterns of regional diastolic function in the normal human left ventricle: an ultrafast computed tomographic study.

The detailed evaluation of regional diastolic filling at multiple ventricular levels in the normal human left ventricle has not previously been reported. Ultrafast computed tomography was used to characterize global and regional early diastolic filling in the left ventricle of 11 normal male volunteers. Regional early diastolic filling data from six distinct ventricular levels (apex to base) were fit to a third-order polynomial curve, and the peak rate of diastolic filling and time of peak filling were determined. Peak filling rate was 259 +/- 17 ml/s (+/- SEM) as a global average, where peak filling rate referenced to end-diastolic volume and stroke volume across the levels examined was 3.78 +/- 0.17 s-1 and 4.83 +/- 0.20 s-1, respectively. Average filling fraction was 39 +/- 1%, and time to peak filling from end-systole was 145 +/- 5 ms. Regional (tomographic) peak filling rates, except for the most apical level examined, were not statistically different across the ventricle. Filling fraction and time to peak filling were remarkably constant from one level to another. However, reference of regional peak filling rate to regional end-diastolic volume demonstrated significant nonuniformity from apex (120% of average for all levels) to base (87% of average for all levels). Peak filling rate referenced to tomographic stroke volume was less variable and not statistically different across the ventricle as a whole.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic value of coronary calcification and angiographic stenoses in patients undergoing coronary angiography.

OBJECTIVES: This investigation sought to determine the relative prognostic value of coronary calcific deposits and coronary angiographic findings for predicting coronary heart disease-related events in patients referred for angiography. BACKGROUND: The relation among coronary calcification, coronary stenoses and coronary heart disease-related events is of interest on a clinical as well as a pathophysiologic basis. METHODS: Four hundred ninety-one symptomatic patients underwent coronary angiography and electron beam computed tomography at five different centers between April 1989 and December 1993. The electron beam computed tomograms were interpreted by a cardiologist with no knowledge of the coronary angiographic and clinical data. Receiver operating characteristic (ROC) curves were constructed to determine the relation between electron beam computed tomographic and coronary angiographic findings. A follow-up telephone survey was completed in 86% of patients. The records for all patients who died or were admitted to the hospital for chest pain or suspected myocardial infarction were reviewed by three other cardiologists with no knowledge of the coronary angiographic and electron beam computed tomographic study results. RESULTS: The mean (+/- SE) area under the ROC curve was 0.75 +/- 0.02 for the coronary calcium score, indicating moderate discriminatory power for this score for predicting angiographic findings. Thirteen coronary heart disease-related deaths and eight nonfatal acute infarctions occurred over 30 +/- 13 months. Scores were sorted in ascending order and divided into quartiles of equal size. One patient in the first quartile had a fatal myocardial infarction (coronary calcium score range 0 to 2.1); 2 in the second quartile (range 2.1 to 75.3), 8 in the third quartile (range 75.3 to 397.1) and 10 in the fourth quartile (> 397.1) had a coronary heart disease-related event. Application of bivariate logistic regression showed that log score but not number of angiographically diseased vessels significantly predicted the probability of a coronary heart disease-related event occurring during follow-up. CONCLUSIONS: Electron beam computed tomographic calcium scores correlate moderately well with angiographic findings. These scores predict coronary heart disease-related events in patients undergoing angiography as well as do the number of angiographically affected arteries.

Coronary risk factors measured in childhood and young adult life are associated with coronary artery calcification in young adults: the Muscatine Study.

OBJECTIVES: This study was designed to estimate the prevalence of coronary artery calcification in young adult men and women and to examine the association between the presence of coronary artery calcification and coronary risk factors measured in childhood and young adult life. BACKGROUND: Electron beam computed tomography is a sensitive, noninvasive method for detecting coronary artery calcification, a marker of the atherosclerotic process. Coronary artery calcification is associated with coronary risk factors in older adults. METHODS: Subjects (197 men, 187 women) had coronary risk factors measured in childhood (mean age 15 years) and twice during young adult life (mean ages 27 and 33 years). Each underwent an electron beam computed tomographic study at their second young adult examination. RESULTS: The prevalence of coronary artery calcification was 31% in men and 10% in women. Increased body size, increased blood pressure and decreased high density lipoprotein (HDL) cholesterol levels were the coronary risk factors that showed the strongest association with coronary artery calcification. Significant odds ratios for coronary artery calcification, using standardized risk factor measurements at a mean age of 33 years in men and women, respectively, were 6.4 and 13.6 for the highest decile of body mass index, 6.4 and 6.4 for the highest decile of systolic blood pressure and 4.3 and 4.7 for the lowest decile of HDL cholesterol. CONCLUSIONS: Coronary artery calcification is more prevalent in men in this young adult population. Coronary risk factors measured in children and young adults are associated with the early development of coronary artery calcification. Increased body mass index measured during childhood and young adult life and increased blood pressure and decreased HDL cholesterol levels measured during young adult life are associated with the presence of coronary artery calcification in young adults.

Sensitivity and specificity of assessing coronary bypass graft patency with ultrafast computed tomography: results of a multicenter study.

Because a significant number of all patients seen by cardiologists have had coronary bypass surgery, a relatively noninvasive method of assessing coronary bypass graft patency would be very helpful. Ultrafast computed tomography, by virtue of its rapid data acquisition time and reasonable spatial resolution, may be useful in this regard. To determine the sensitivity, specificity and predictive accuracy of this imaging modality as compared with cardiac catheterization, a multicenter study was undertaken. There were two parts to the study. Part I involved the evaluation of 179 grafts in 74 patients studied in the five participating centers between March 1985 and August 1986. Twenty-nine percent of these graft studies were found to be technically inadequate and were excluded before patency determinations began. The remaining group of 127 bypass grafts in 62 patients had studies adequate for interpretation. Fifty-one grafts were to the left anterior descending coronary artery or a diagonal branch, 37 to branches of the left circumflex artery and 28 to the right coronary artery or a posterior descending vessel; in addition, there were 11 internal mammary artery bypass grafts primarily into the left anterior descending or diagonal artery distribution. The sensitivity of detecting angiographically open grafts was 93.4%, the specificity of detecting angiographically closed grafts 88.9% and the predictive accuracy was 92.1%. A subsequent study (Part 2) was performed 9 months later to assess the ability to carry out technically adequate examinations. Of the 138 consecutive graft examinations (50 patients) included in this part of the study, 94.2% of the examinations were found to be technically adequate.(ABSTRACT TRUNCATED AT 250 WORDS)

Gene trapping of two novel genes, Hzf and Hhl, expressed in hematopoietic cells.

Using an expression gene trapping strategy, we have identified and characterized two novel hematopoietic genes, Hzf and Hhl. Embryonic stem (ES) cells containing a gene trap vector insertion were cultured on OP9 stromal cells to induce hematopoietic differentiation and screened for lacZ reporter gene expression. Two ES clones displaying lacZ expression within hematopoietic cells in vitro were used to generate mice containing the gene trap integrations. Paralleling this in vitro expression pattern, both Hzf and Hhl were expressed in a tissue-specific manner during hematopoietic development in vivo. Hzf encodes a novel protein containing three C(2)H(2)-type zinc fingers predominantly expressed in megakaryocytes and CFU-GEMM. Hhl encodes a novel protein containing a putative phosphotyrosine binding (PTB) domain expressed in megakaryocytes, CFU-GEMM and BFU-E. These results demonstrate the utility of expression trapping to identify novel hematopoietic genes. Future studies of Hzf and Hhl should provide valuable information on the role these genes play during megakaryocytopoiesis.

Further analysis of a doctor-patient nonverbal communication instrument.

This study examines the reliability and validity of the relational communication scale for observational measurement (RCS-O) using a random sample of 80 videotaped interactions of medical students interviewing standardized patients (SPs). The RCS-O is a 34-item instrument designed to measure the nonverbal communication of physicians interacting with patients. The instrument was applied and examined in two different interview scenarios. In the first scenario (year 1), the medical student's interview objective is to demonstrate patient-centered interviewing skills as the SP presents with a psychosocial concern. In the second scenario (year 3), the student's interview objective is to demonstrate both doctor-centered and patient-centered skills as the SP presents with a case common in primary care. In the year 1 scenario, 19 of the 34 RCS-O items met acceptable levels of inter-rater agreement and reliability. In the year 3 scenario, 26 items met acceptable levels of inter-rater agreement and reliability. Factor analysis indicated that in both scenarios each of the four primary relational communication dimensions was salient: intimacy, composure, formality, and dominance. Measures of correlation and differences involving the RCS-O dimensions and structural features of the interviews (e.g., number of questions asked by the medical student) are examined.

Analysis of movement of intrathoracic neoplasms using ultrafast computerized tomography.

Twenty patients with intrathoracic neoplasms were evaluated with ultrafast (cine) computerized tomography to determine the contribution of tumor motion to geographic errors. The treatment portals were setup with conventional simulation techniques and then scanned with cine computerized tomography. Eight tomographic levels were studied, 10 images per level over 7 seconds time. Major geographic misses were detected in three patients (15%), and minor geographic misses in an additional three (15%). The greatest tumor movement was noted in lesions located adjacent to the heart or aorta or near the diaphragm. Five of six hilar lesions showed significant lateral motion (average = 9.2 mm) with cardiac contraction, and three of four lower lobe lesions showed significant craniocaudal movement with respiration. Mediastinal lesions moved an average of 8.7 mm laterally. Lesions in the upper lobes showed minimal movement (average = 2.2 mm), and tumors attached to the chest wall showed no measurable movement.

Evidence that drug-resistant alloreactive T cells may contribute to human graft rejection.

The objective of our study was to determine whether resistance to immunosuppressive drugs by transplant recipient's T cells could contribute to continued graft rejection, in spite of immunosuppressive therapy. The T cell lines used in this series of experiments were originally established from T cells that had infiltrated kidney or liver grafts and initiated rejections in patients receiving immunosuppressive drugs, including the purine analogue azathioprine (AZ). We have used a proliferation assay and the Strauss-Albertini test to analyze the T cell lines. Both assays use 6-thioguanine (6-TG), an amino derivative of AZ, as the selective agent to measure the resistance to AZ. Although the frequency of 6-TG-resistant variants in the majority of T cell lines closely resembled the frequency found in peripheral blood lymphocytes of controls, we identified four cell lines that demonstrated virtually complete resistance to the purine analogue 6-TG in both assays. These observations indicate that a more effective immunosuppressive treatment may be achieved by using a combination of drugs.

Relative accuracy of three scintigraphic methods for determination of right ventricular ejection fraction: a correlative study with ultrafast computed tomography.

The accuracy of three scintigraphic methods for determination of right ventricular ejection fraction (RVEF) was tested in 29 patients using ultrafast computed tomography (UFCT) as the gold standard. RVEF measurements by the ECG-gated first-pass approach showed excellent correlation with the UFCT results (r = 0.96, y = 0.06 + 0.91x), while both the standard gated acquisition blood-pool imaging (r = 0.71, y = 0.14 + 0.59x) and the nongated first-pass curve approach (r = 0.63, y = 0.18 + 0.37x) significantly underestimated RVEF. The error can be ascribed to partial inclusion of the atrial activity in the region assigned to the right ventricle. The tricuspid valve plane was found to move by a distance equal to 9%-33% (mean = 20%) of the right ventricular long-axis between systole and diastole. This translational motion was more pronounced with higher EFs.