Dose Comparison Study of Allogeneic Mesenchymal Stem Cells in Patients With Ischemic Cardiomyopathy (The TRIDENT Study).

RATIONALE: Cell dose and concentration play crucial roles in phenotypic responses to cell-based therapy for heart failure. OBJECTIVE: To compare the safety and efficacy of 2 doses of allogeneic bone marrow-derived human mesenchymal stem cells identically delivered in patients with ischemic cardiomyopathy. METHODS AND RESULTS: Thirty patients with ischemic cardiomyopathy received in a blinded manner either 20 million (n=15) or 100 million (n=15) allogeneic human mesenchymal stem cells via transendocardial injection (0.5 cc per injection × 10 injections per patient). Patients were followed for 12 months for safety and efficacy end points. There were no treatment-emergent serious adverse events at 30 days or treatment-related serious adverse events at 12 months. The Major Adverse Cardiac Event rate was 20.0% (95% confidence interval [CI], 6.9% to 50.0%) in 20 million and 13.3% (95% CI, 3.5% to 43.6%) in 100 million (P=0.58). Worsening heart failure rehospitalization was 20.0% (95% CI, 6.9% to 50.0%) in 20 million and 7.1% (95% CI, 1.0% to 40.9%) in 100 million (P=0.27). Whereas scar size reduced to a similar degree in both groups: 20 million by -6.4 g (interquartile range, -13.5 to -3.4 g; P=0.001) and 100 million by -6.1 g (interquartile range, -8.1 to -4.6 g; P=0.0002), the ejection fraction improved only with 100 million by 3.7 U (interquartile range, 1.1 to 6.1; P=0.04). New York Heart Association class improved at 12 months in 35.7% (95% CI, 12.7% to 64.9%) in 20 million and 42.9% (95% CI, 17.7% to 71.1%) in 100 million. Importantly, proBNP (pro-brain natriuretic peptide) increased at 12 months in 20 million by 0.32 log pg/mL (95% CI, 0.02 to 0.62; P=0.039), but not in 100 million (-0.07 log pg/mL; 95% CI, -0.36 to 0.23; P=0.65; between group P=0.07). CONCLUSIONS: Although both cell doses reduced scar size, only the 100 million dose increased ejection fraction. This study highlights the crucial role of cell dose in the responses to cell therapy. Determining optimal dose and delivery is essential to advance the field, decipher mechanism(s) of action and enhance planning of pivotal Phase III trials. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02013674.

Assessment of Diastolic Function in Hypertrophic Cardiomyopathy by Computed Tomography-Derived Analysis of Left Ventricular Filling.

OBJECTIVES: Hypertrophic cardiomyopathy (HCM) is characterized by diastolic dysfunction, which is difficult to assess by noninvasive methods. We hypothesized that measurement of simultaneous left ventricular (LV) and left atrial (LA) volume changes by cardiac computed tomography would be useful in the assessment of diastolic function in HCM. METHODS: We studied 21 patients with HCM and 21 age-matched controls. The LA and LV volumes were calculated and early and late diastolic volume changes derived. RESULTS: The HCM patients had significantly larger LA volumes and reduced LA total emptying fraction (30 ± 7% vs 42 ± 6%; P < 0.0001). Conduit volume was increased (30 ± 6 vs 22 ± 4 mL/m; P < 0.0001) and contributed a significantly higher proportion of total LV diastolic filling, suggesting that passive filling of the LV compensates for LA dysfunction, but at the expense of increased pulmonary filling pressure. CONCLUSIONS: This study suggests that simultaneous depiction of computed tomography-derived LV and LA volume changes can characterize diastolic dysfunction in HCM.

Does transendocardial injection of mesenchymal stem cells improve myocardial function locally or globally?: An analysis from the Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis (POSEIDON) randomized trial.

RATIONALE: Transendocardial stem cell injection (TESI) with mesenchymal stem cells improves remodeling in chronic ischemic cardiomyopathy, but the effect of the injection site remains unknown. OBJECTIVE: To address whether TESI exerts its effects at the site of injection only or also in remote areas, we hypothesized that segmental myocardial scar and segmental ejection fraction improve to a greater extent in injected than in noninjected segments. METHODS AND RESULTS: Biplane ventriculographic and endocardial tracings were recorded. TESI was guided to 10 sites in infarct-border zones. Sites were mapped according to the 17-myocardial segment model. As a result, 510 segments were analyzed in 30 patients before and 13 months after TESI. Segmental early enhancement defect (a measure of scar size) was reduced by TESI in both injected (-43.7 ± 4.4%; n=95; P<0.01) and noninjected segments (-25.1 ± 7.8%; n=148; P<0.001; between-group comparison P<0.05). Conversely, segmental ejection fraction (a measure of contractile performance) improved in injected scar segments (19.9 ± 3.3-26.3 ± 3.5%; P=0.003) but not in noninjected scar segments (21.3 ± 2.6-23.5 ± 3.2%; P=0.20; between-group comparison P<0.05). Furthermore, segmental ejection fraction in injected scar segments improved to a greater degree in patients with baseline segmental ejection fraction <20% (12.1 ± 1.2-19.9 ± 2.7%; n=18; P=0.003), versus <20% (31.7 ± 3.4-35.5 ± 3.3%; n=12; P=0.33, between-group comparison P<0.0001). CONCLUSIONS: These findings illustrate a dichotomy in regional responses to TESI. Although scar size reduction was evident in all scar segments, scar size reduction and ventricular functional responses preferentially occurred at the sites of TESI versus non-TESI sites. Furthermore, improvement was greatest when segmental left ventricular dysfunction was severe.

Cardiac Physiology for Radiologists: Review of Relevant Physiology for Interpretation of Cardiac MR Imaging and CT.

Cardiac computed tomography (CT) and magnetic resonance (MR) imaging provide clinicians with important insights into cardiac physiology and pathology. However, not all radiologists understand the language and concepts of cardiac physiology that are used daily by cardiologists. This review article covers basic cardiac physiology as it relates to cardiac CT and MR imaging. Topics include a review of the cardiac cycle and left ventricular pressure-volume loops as they relate to different pathologic states, evaluation of cardiac function, and calculation of key parameters such as left ventricular volumes and the ejection fraction. The hemodynamics of cardiac shunts are covered, with an emphasis on factors important to cardiologists, including the ratio of pulmonary flow to systemic flow. Additionally, valvular physiologic function is reexamined, with a focus on understanding pressure gradients within the heart and also the changes associated with valvular pathologic conditions, including measurement of regurgitant fractions in patients with valvular insufficiency. Understanding these basic concepts will help radiologists tailor the reporting of cardiac studies to clinically relevant information.

ECG-gated MDCT after aortic and mitral valve surgery.

OBJECTIVE: The purpose of this article is to review the utility of ECG-gated MDCT in evaluating postsurgical findings in aortic and mitral valves. Normal and pathologic findings after aortic and mitral valve corrective surgery are shown in correlation with the findings of the traditionally used imaging modalities echocardiography and fluoroscopy to assist in accurate noninvasive anatomic and dynamic evaluation of postsurgical valvular abnormalities. CONCLUSION: Because of its superior spatial and adequate temporal resolution, ECG-gated MDCT has emerged as a robust diagnostic tool in the evaluation and treatment of patients with postsurgical valvular abnormalities.

Transendocardial mesenchymal stem cells and mononuclear bone marrow cells for ischemic cardiomyopathy: the TAC-HFT randomized trial.

IMPORTANCE: Whether culture-expanded mesenchymal stem cells or whole bone marrow mononuclear cells are safe and effective in chronic ischemic cardiomyopathy is controversial. OBJECTIVE: To demonstrate the safety of transendocardial stem cell injection with autologous mesenchymal stem cells (MSCs) and bone marrow mononuclear cells (BMCs) in patients with ischemic cardiomyopathy. DESIGN, SETTING, AND PATIENTS: A phase 1 and 2 randomized, blinded, placebo-controlled study involving 65 patients with ischemic cardiomyopathy and left ventricular (LV) ejection fraction less than 50% (September 1, 2009-July 12, 2013). The study compared injection of MSCs (n=19) with placebo (n = 11) and BMCs (n = 19) with placebo (n = 10), with 1 year of follow-up. INTERVENTIONS: Injections in 10 LV sites with an infusion catheter. MAIN OUTCOMES AND MEASURES: Treatment-emergent 30-day serious adverse event rate defined as a composite of death, myocardial infarction, stroke, hospitalization for worsening heart failure, perforation, tamponade, or sustained ventricular arrhythmias. RESULTS: No patient had a treatment-emergent serious adverse events at day 30. The 1-year incidence of serious adverse events was 31.6% (95% CI, 12.6% to 56.6%) for MSCs, 31.6% (95% CI, 12.6%-56.6%) for BMCs, and 38.1% (95% CI, 18.1%-61.6%) for placebo. Over 1 year, the Minnesota Living With Heart Failure score improved with MSCs (-6.3; 95% CI, -15.0 to 2.4; repeated measures of variance, P=.02) and with BMCs (-8.2; 95% CI, -17.4 to 0.97; P=.005) but not with placebo (0.4; 95% CI, -9.45 to 10.25; P=.38). The 6-minute walk distance increased with MSCs only (repeated measures model, P = .03). Infarct size as a percentage of LV mass was reduced by MSCs (-18.9%; 95% CI, -30.4 to -7.4; within-group, P = .004) but not by BMCs (-7.0%; 95% CI, -15.7% to 1.7%; within-group, P = .11) or placebo (-5.2%; 95% CI, -16.8% to 6.5%; within-group, P = .36). Regional myocardial function as peak Eulerian circumferential strain at the site of injection improved with MSCs (-4.9; 95% CI, -13.3 to 3.5; within-group repeated measures, P = .03) but not BMCs (-2.1; 95% CI, -5.5 to 1.3; P = .21) or placebo (-0.03; 95% CI, -1.9 to 1.9; P = .14). Left ventricular chamber volume and ejection fraction did not change. CONCLUSIONS AND RELEVANCE: Transendocardial stem cell injection with MSCs or BMCs appeared to be safe for patients with chronic ischemic cardiomyopathy and LV dysfunction. Although the sample size and multiple comparisons preclude a definitive statement about safety and clinical effect, these results provide the basis for larger studies to provide definitive evidence about safety and to assess efficacy of this new therapeutic approach. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00768066.

Comparison of allogeneic vs autologous bone marrow­derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial.

CONTEXT: Mesenchymal stem cells (MSCs) are under evaluation as a therapy for ischemic cardiomyopathy (ICM). Both autologous and allogeneic MSC therapies are possible; however, their safety and efficacy have not been compared. OBJECTIVE: To test whether allogeneic MSCs are as safe and effective as autologous MSCs in patients with left ventricular (LV) dysfunction due to ICM. DESIGN, SETTING, AND PATIENTS: A phase 1/2 randomized comparison (POSEIDON study) in a US tertiary-care referral hospital of allogeneic and autologous MSCs in 30 patients with LV dysfunction due to ICM between April 2, 2010, and September 14, 2011, with 13-month follow-up. INTERVENTION: Twenty million, 100 million, or 200 million cells (5 patients in each cell type per dose level) were delivered by transendocardial stem cell injection into 10 LV sites. MAIN OUTCOME MEASURES: Thirty-day postcatheterization incidence of predefined treatment-emergent serious adverse events (SAEs). Efficacy assessments included 6-minute walk test, exercise peak VO2, Minnesota Living with Heart Failure Questionnaire (MLHFQ), New York Heart Association class, LV volumes, ejection fraction (EF), early enhancement defect (EED; infarct size), and sphericity index. RESULTS: Within 30 days, 1 patient in each group (treatment-emergent SAE rate, 6.7%) was hospitalized for heart failure, less than the prespecified stopping event rate of 25%. The 1-year incidence of SAEs was 33.3% (n = 5) in the allogeneic group and 53.3% (n = 8) in the autologous group (P = .46). At 1 year, there were no ventricular arrhythmia SAEs observed among allogeneic recipients compared with 4 patients (26.7%) in the autologous group (P = .10). Relative to baseline, autologous but not allogeneic MSC therapy was associated with an improvement in the 6-minute walk test and the MLHFQ score, but neither improved exercise VO2 max. Allogeneic and autologous MSCs reduced mean EED by −33.21% (95% CI, −43.61% to −22.81%; P < .001) and sphericity index but did not increase EF. Allogeneic MSCs reduced LV end-diastolic volumes. Low-dose concentration MSCs (20 million cells) produced greatest reductions in LV volumes and increased EF. Allogeneic MSCs did not stimulate significant donor-specific alloimmune reactions. CONCLUSIONS: In this early-stage study of patients with ICM, transendocardial injection of allogeneic and autologous MSCs without a placebo control were both associated with low rates of treatment-emergent SAEs, including immunologic reactions. In aggregate, MSC injection favorably affected patient functional capacity, quality of life, and ventricular remodeling. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01087996.

Coping with war mass casualties in a hospital under fire: the radiology experience.

OBJECTIVE: We report the role of the imaging department at a level 1 trauma center during the Second Lebanon War (summer 2006). Our institution received 849 military and civilian casualties, an average of 25 war-injured patients per day, 338 with acute traumatic stress disorders and 511 physically injured, coming in waves after a rocket attack or a battle confrontation. About 12 potentially critical physically injured patients per day were referred to the imaging department for sometimes complex imaging procedures. The unpredictable waves of casualties and nature of the injuries forced us to reorganize our routine workflow to provide adequate care to casualties and to nonemergent patients. Our nurses' station was transformed into a small emergency department. The radiology staff was distributed into 12 diagnostic stations, providing 24-hour service. Communication was improved by means of walkie-talkies. Three ultrasound units were placed at the emergency department for immediate focused assessment with sonography for trauma performance enabling initial triage of patients. The site and extent of injuries were accurately diagnosed on CT and CT angiography. Digital angiography allowed definitive vascular diagnosis and interventional procedures. CONCLUSION: Adequate communication, strict workflow, and correct use of imaging protocols ensured optimal triage, diagnosis, and therapy of casualties while maintaining care for nonwar patients.

Quantitative evaluation of regional left ventricular function by multidetector computed tomography.

OBJECTIVE: : Because most contemporary workstations offer quantitative analysis of regional function by multidetector computed tomography, we aimed to establish typical values for normal, hypokinetic, and akinetic regions, and to establish optimal thresholds to differentiate between normal and abnormal values. METHODS: : For 33 patients, quantitative regional functional parameters were compared with visual analysis by both multidetector computed tomography and echocardiography. Normal values were established to normalize for segmental variability. Optimal thresholds were established to differentiate between normal and abnormal segments by receiver operating characteristic analysis. RESULTS: : Akinetic, hypokinetic, and normokinetic segments demonstrated significant differences (P < 0.0001) for end-systolic thickness (mean [95% confidence interval], 9.4 [4.5-14.3], 11.7 [7.2-16.2], and 14.3 mm [8.2-20.3 mm]), respectively; thickening, 24% [-22% to 71%], 45% [-16% to 106%], and 82% [10%-154%]), respectively; and motion, 3.5 [-2.0 to 8.9], 6.1 [-0.2 to 12.4], and 8.5 mm [1.8-15.3 mm], respectively). Thickening performed best with area under the curve of 0.87 and sensitivity equal to specificity of 82%. Intraobserver variability was good, but interobserver variability was only moderate. CONCLUSIONS: : Quantification of regional myocardial function can be performed to assist the physician in mapping left ventricular function.

Cardiology consultation as a gatekeeper prior to cardiac multi-detector computed tomography scan.

BACKGROUND: Multi-detector computed tomography has advanced enormously and now enables non-invasive evaluation of coronary arteries as well as cardiac anatomy, function and perfusion. However, the role of cardiac MDCT is not yet determined in the medical community and, consequently, many clinically unnecessary scans are performed solely on a self-referral basis. OBJECTIVES: To prospectively evaluate the role of a cardiologist consultation and recommendation prior to the scan, and the influence on the diagnostic yield of cardiac MDCT. METHODS: In our center a CT service was initiated, but with the prerequisite approval of a cardiologist before performance of the CT. Each individual who wanted and was willing to pay for a cardiac CT was interviewed by an experienced cardiologist who determined whether cardiac MDCT was the most appropriate next test in the cardiovascular evaluation. Subjects were classified into three groups: a) those with a normal or no prior stress test, no typical symptoms and no significant risk factors of coronary artery disease were recommended to perform a stress test or to remain under close clinical follow-up without MDCT; b) those with an equivocal stress test, atypical symptoms and/or significant risk factors were allowed to have cardiac MDCT; and c) those with positive stress test or clinically highly suspected CAD were advised to go directly to invasive coronary angiography. CT findings were categorized as normal CAD (normal calcium score and no narrowings), < 50% and > 50% CAD. RESULTS: A total of 254 people were interviewed, and in only 39 cases did the cardiologist approve the CT. However, 61 of the 215, despite our recommendation not to undergo CT, decided to have the scan. Assessment of the 100 cases that underwent MDCT showed a statistically significant better discrimination of significant CAD, according to the cardiologist's recommendation: MDCT not recommended in 3/54 (6%) vs. MDCT recommended in 12/39 (31%) vs. recommended invasive coronary angiography in 4/7 (57%)(P<0.001). CONCLUSIONS: Detection of coronary calcification, as well as MDCT angiography can provide clinically useful information if applied to suitable patient groups. It is foreseeable that MDCT angiography will become part of the routine workup in some subsets of patients with suspected CAD. Selection of patients undergoing MDCT scans by a cardiologist improves the ability of the test to stratify patients, preventing unnecessary scans in both high and low risk patients.

Antegrade pyelography versus unenhanced multidetector CT in the assessment of urinary-tract stones after percutaneous nephrostomy insertion: a prospective blinded study.

BACKGROUND AND PURPOSE: In patients with a percutaneous nephrostomy tube (PCN) inserted for symptomatic stone disease, antegrade pyelography is an accepted modality to assess the collecting system and residual stone status prior to PCN removal. Recently, unenhanced multidetector CT (UMDCT) has shown its superiority for the assessment of urinary-tract stones. Comparison of UMDCT with antegrade pyelography has never been done; hence, our aim was to compare the two methods for the assessment of urinary stones in patients with a PCN. PATIENTS AND METHODS: Between July 2004 and July 2005, we prospectively imaged 49 consecutive patients with known urinary-tract stone disease who had PCN (27 men and 22 women; average age 57 +/- 20 years; range 4-88 years). All patients underwent UMDCT and antegrade pyelography within 24 hours. Both examinations were prospectively and blindly evaluated by two attending radiologists for the presence, location, and size of urinary-tract stones. RESULTS: According to the findings of both imaging modalities, 18 patients were stone free, and 31 patients had urinary stones. In 20 of the latter 31 patients (64.5%), the urinary stones were diagnosed only by UMDCT. Antegrade pyelography missed renal as well as ureteral stones, with a significant mean size (5.1 x 6.2 mm, and 6 x 5.3 mm, respectively). Antegrade pyelography missed radiolucent (8/20) as well as radiopaque (12/20) stones. In 11 of the 31 patients (35.5%), urinary stones were diagnosed by both UMDCT and antegrade pyelography. The average size of these renal stones was 6 x 11 mm, and the mean ureteral stone size was 11 x 13 mm. In 64% (7/11), the stones were radiolucent and in 36% (4/11) radiopaque. There was no patient in whom urinary stones were diagnosed by antegrade pyelography but missed by UMDCT. CONCLUSIONS: Unenhanced multidetector CT is more accurate than antegrade pyelography via a PCN for the assessment of urinary-tract stones, with the advantage of reducing the risks of contrast injection side effects.

Randomized Comparison of Allogeneic Versus Autologous Mesenchymal Stem Cells for Nonischemic Dilated Cardiomyopathy: POSEIDON-DCM Trial.

BACKGROUND: Although human mesenchymal stem cells (hMSCs) have been tested in ischemic cardiomyopathy, few studies exist in chronic nonischemic dilated cardiomyopathy (NIDCM). OBJECTIVES: The authors conducted a randomized comparison of safety and efficacy of autologous (auto) versus allogeneic (allo) bone marrow-derived hMSCs in NIDCM. METHODS: Thirty-seven patients were randomized to either allo- or auto-hMSCs in a 1:1 ratio. Patients were recruited between December 2011 and July 2015 at the University of Miami Hospital. Patients received hMSCs (100 million) by transendocardial stem cell injection in 10 left ventricular sites. Treated patients were evaluated at baseline, 30 days, and 3-, 6-, and 12-months for safety (serious adverse events [SAE]), and efficacy endpoints: ejection fraction, Minnesota Living with Heart Failure Questionnaire, 6-min walk test, major adverse cardiac events, and immune biomarkers. RESULTS: There were no 30-day treatment-emergent SAEs. Twelve-month SAE incidence was 28.2% with allo-hMSCs versus 63.5% with auto-hMSCs (p = 0.1004 for the comparison). One allo-hMSC patient developed an elevated (>80) donor-specific calculated panel reactive antibody level. The ejection fraction increased in allo-hMSC patients by 8.0 percentage points (p = 0.004) compared with 5.4 with auto-hMSCs (p = 0.116; allo vs. auto p = 0.4887). The 6-min walk test increased with allo-hMSCs by 37.0 m (p = 0.04), but not auto-hMSCs at 7.3 m (p = 0.71; auto vs. allo p = 0.0168). MLHFQ score decreased in allo-hMSC (p = 0.0022) and auto-hMSC patients (p = 0.463; auto vs. allo p = 0.172). The major adverse cardiac event rate was lower, too, in the allo group (p = 0.0186 vs. auto). Tumor necrosis factor-α decreased (p = 0.0001 for each), to a greater extent with allo-hMSCs versus auto-hMSCs at 6 months (p = 0.05). CONCLUSIONS: These findings demonstrated safety and clinically meaningful efficacy of allo-hMSC versus auto-hMSC in NIDCM patients. Pivotal trials of allo-hMSCs are warranted based on these results. (Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis in Dilated Cardiomyopathy [PoseidonDCM]; NCT01392625).

Comparison of multidetector computed tomography versus echocardiography for assessing regional left ventricular function.

Multidetector computed tomography (MDCT) of the heart is a rapidly developing technique mainly used to evaluate the coronary arteries. However, it is also capable of evaluating ventricular function. It compares well with magnetic resonance imaging in calculating volumes and ejection fractions, but little has been reported on its ability to assess left ventricular (LV) segmental wall motion (LVSWM). This study compared semiquantitative LVSWM scoring by MDCT with echocardiography as the gold standard. Thirty-nine patients underwent MDCT angiography on a 16-slice scanner. Short- and long-axis LV slices were created at different phases of the cardiac cycle and visually evaluated using cine mode. Echocardiography was performed <48 hours after MDCT for 21 patients after acute myocardial infarctions and <1 month after MDCT for 18 patients without acute myocardial infarctions. Two blinded observers scored the MDCT and echocardiographic examinations according to the 16-segment model, scoring each segment from 1 (normal) to 3 (akinetic). Segmental dysfunction was found in 27 patients by echocardiography and in 24 by MDCT. An identical score was given by the 2 methods in 502 of 616 assessable segments (82%). Using a binary analysis (normal or abnormal), there was 89% agreement (546 of 616 segments). MDCT had a sensitivity of 66% (103 of 155 segments) and a specificity of 96% (443 of 461 segments) compared with echocardiography as the gold standard. Most disagreements occurred in the right coronary artery segments. In conclusion, MDCT can be used to evaluate LVSWM, showing good agreement with echocardiography, except for the right coronary artery segments.

Effect of aging on human mesenchymal stem cell therapy in ischemic cardiomyopathy patients.

BACKGROUND: The role of patient age in the efficacy of mesenchymal stem cell (MSC) therapy in ischemic cardiomyopathy (ICM) is controversial. OBJECTIVES: This study sought to determine whether the therapeutic effect of culture-expanded MSCs persists, even in older subjects. METHODS: Patients with ICM who received MSCs via transendocardial stem cell injection (TESI) as part of the TAC-HFT (Transendocardial Autologous Cells in Ischemic Heart Failure) (n = 19) and POSEIDON (Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis) (n = 30) clinical trials were divided into 2 age groups: younger than 60 and 60 years of age and older. Functional capacity was measured by 6-min walk distance (6MWD) and quality of life using the Minnesota Living With Heart Failure Questionnaire (MLHFQ) score, measured at baseline, 6 months, and 1 year post-TESI. Various cardiac imaging parameters, including absolute scar size, were compared at baseline and 1 year post-TESI. RESULTS: The mean 6MWD was similar at baseline and increased at 1 year post-TESI in both groups: 48.5 ± 14.6 m (p = 0.001) for the younger and 35.9 ± 18.3 m (p = 0.038) for the older participants (p = NS between groups). The older group exhibited a significant reduction in MLHFQ score (-7.04 ± 3.54; p = 0.022), whereas the younger than 60 age group had a borderline significant reduction (-11.22 ± 5.24; p = 0.058) from baseline (p = NS between groups). Although there were significant reductions in absolute scar size from baseline to 1 year post-TESI, the effect did not differ by age. CONCLUSIONS: MSC therapy with TESI in ICM patients improves 6MWD and MLHFQ score and reduces myocardial infarction size. Importantly, older individuals did not have an impaired response to MSC therapy.

Feasibility study of ultrasonic fatty liver biopsy: texture vs. attenuation and backscatter.

The objective of this study was to compare textural to attenuation/backscatter indices of fatty liver correlated to histology to suggest the better approach for an objective noninvasive ultrasonic "biopsy". Forty-four patients with severe steatosis by histopathology were selected for this study. Ten patients had "pure" fatty liver and 34 had in addition fibrosis and/or inflammation. Ultrasonic images were acquired before needle insertion. The ROI used for biopsy was marked on the ultrasonic image and characterized by three attenuation/backscatter and 18 textural related indices. Statistical analysis was performed using logistic regression. Twenty-one healthy subjects served as control. The attenuation/backscatter indices were superior to textural indices in differentiating between the categories studied. Pure fatty livers could be reliably identified (AUC = 1, SE = 0). Among the 18 textural indices, "co-occurrences sum entropy" and "co-occurrences entropy" presented the best results. Attenuation/backscatter based indices appear to have better potential than the textural based indices.

The role of selective computed tomography in the diagnosis and management of suspected acute appendicitis.

The negative appendectomy rate in patients with clinically diagnosed acute appendicitis is 20 to 40 per cent. Recently CT has emerged as a powerful diagnostic tool in the evaluation of suspected appendicitis and its routine use has been advocated. The objective of this study was to evaluate the impact of selective use of abdominal CT on the negative appendectomy rate. Three hundred eight patients were enrolled in this prospective study. Abdominal CT was performed in patients with uncertain clinical signs of appendicitis. CT was not performed in patients with either a very high or a very low index of suspicion. The results were compared with a retrospective analysis of 85 consecutive patients operated by clinical diagnosis alone. One hundred twenty-seven patients had a final diagnosis of acute appendicitis. CT was performed in 198 patients (64%). The sensitivity, specificity, and accuracy of CT scans were 91, 92, and 91 per cent, respectively. Surgical management plans were altered in 54 patients after obtaining the CT results; unnecessary delay in surgical treatment or unnecessary operations were prevented in 28 and 26 patients, respectively. In addition CT detected unrelated pathologies in 23 patients. CT was not performed in patients with low index of suspicion and none were found to suffer from acute appendicitis. The negative appendectomy rate was 17 per cent (7% men and 24% women) in patients selected for surgery on the basis of very high clinical suspicion alone. Overall the negative appendectomy rate with the selective use of CT was 16 per cent, which is significantly lower than the rate achieved by diagnosing patients on clinical grounds alone (24%). CT is highly accurate in diagnosing or ruling out acute appendicitis and may substantially decrease the negative appendectomy rate as well as unnecessary delayed observation. We believe that CT should be performed routinely in women with suspected appendicitis and selectively in men.

Radiographic and electrocardiography-gated noncontrast cardiac CT assessment of lead perforation: modality comparison and interobserver agreement.

BACKGROUND: Pacemaker or implantable cardioverter-defibrillator lead extraction may be required because of infection, malfunction, or breakage. The preprocedural identification of lead tip position may help ensure safe performance of the procedure. OBJECTIVE: To analyze the ability of chest radiography and CT imaging to characterize lead tip position and identify perforation in a population of patients who underwent lead extraction. METHODS: Among patients who underwent lead extraction between November 2008 and April 2011, a nonrandom subset of 50 patients with 116 leads was selected for retrospective analysis. All patients had undergone chest radiography and thin-section electrocardiography-gated noncontrast cardiac CT. Two radiologists independently evaluated the imaging studies, using oblique multiplanar image reconstruction techniques for the CT examinations. Beam hardening artifacts were graded (0-3). Likelihood of perforation on each imaging study was graded on a 5-point scale. RESULTS: Among 116 leads, 17 were identified as perforated on CT, 12 leads were equivocal, and 87 were not perforated. Interobserver agreement for CT perforation vs nonperforation was good (κ = 0.71); weighted kappa for the entire 5-point scale was moderate (κ = 0.54). Beam hardening artifacts were common, with a mean value of 2.1. The 2 observers identified perforation on chest radiography with an average sensitivity of 15% compared with CT. The 2 observers did not agree on any cases of chest radiographic perforation (κ = -0.1). CONCLUSION: Electrocardiography-gated noncontrast cardiac CT imaging with oblique multiplanar analysis can identify potential lead perforation with a moderate-to-good level of interobserver agreement. Chest radiography demonstrates poor sensitivity and interobserver agreement compared with CT.

Imaging in Transcatheter Aortic Valve Replacement (TAVR): role of the radiologist.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is a novel technique developed in the last decade to treat severe aortic stenosis in patients who are non-surgical candidates because of multiple comorbidities. METHODS: Since the technique is performed using a transvascular approach, pre-procedural assessment of the aortic valve apparatus, ascending aorta and vascular access is of paramount importance for both appropriate patient selection and correct device selection. This assessment is performed by a multi-disciplinary team with radiology being an integral and important part. RESULTS: Among imaging modalities, there is growing scientific evidence supporting the crucial role of MDCT in the assessment of the aortic valve apparatus, suitability of the iliofemoral or alternative pathway, and determination of appropriate coaxial angles. MDCT also plays an important role in post-procedure imaging in the assessment of valve integrity and position. CONCLUSION: This review outlines the principal aspects of TAVR, the multidisciplinary approach and utilisation of different imaging modalities, as well as a step-by-step approach to MDCT acquisition protocols, reconstruction techniques, pre-procedure measurements and post-procedure assessment. TEACHING POINTS: • TAVR is a new technique to treat severe aortic stenosis in high-risk and nonsurgical candidates. • MDCT assessment of the aortic annulus is important for appropriate patient and device selection. • Multidisciplinary approach is required for patient selection, procedure planning and performance. • MDCT is required for assessment of the aortic root, iliofemoral or alternative vascular pathway.

Retrograde percutaneous closure of a ventricular septal defect after myectomy for hypertrophic obstructive cardiomyopathy.

In patients with hypertrophic obstructive cardiomyopathy, hemodynamically significant ventricular septal defect after septal myectomy is a rare sequela that warrants closure. Percutaneous closure provides a safer alternative to repeated sternotomy, which is associated with significant morbidity and mortality rates. We report a possibly unique case of successful retrograde percutaneous closure, with an AMPLATZER Muscular VSD Occluder, of an iatrogenic ventricular septal defect consequent to surgical therapy for hypertrophic obstructive cardiomyopathy.