Eduard Ghersin

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.

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.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. # Novelty and Significance {#article-title-37}

16-MDCT coronary angiography versus invasive coronary angiography in acute chest pain syndrome: a blinded prospective study.

OBJECTIVE The purpose of our study was to prospectively evaluate the usefulness of CT coronary angiography versus invasive coronary angiography for the detection of clinically significant coronary artery disease in patients hospitalized for acute chest pain syndrome. SUBJECTS AND METHODS Sixty-six consecutive patients (52 men and 14 women; average age, 57 +/- 11 [SD] years) who were hospitalized for acute chest pain syndrome underwent CT coronary angiography and invasive coronary angiography within an average time interval of 4 days. ECG-gated CT coronary angiography was performed with a 16-MDCT scanner (0.42-sec rotation time, 16 x 0.75 mm detector collimation). Beta-blockers were not administered routinely, and thus the average heart rate was 71 +/- 11 beats per minute. CT coronary angiographic images were evaluated concurrently by two radiologists, who were blinded to invasive coronary angiography results, for stenoses having a diameter of 50% or more, using a 15-segment classification, including all segments 2 mm or more in diameter. The consensus interpretation was compared with results of invasive coronary angiography. RESULTS CT coronary angiography was technically successful in 59 patients (89%). After exclusion of 20 (3.1%) of 649 coronary segments, which were classified as nonevaluable by CT coronary angiography, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of CT coronary angiography for identifying significant coronary artery disease in the remaining 629 coronary segments were 80% (68/85), 89% (482/544), 52% (68/130), 97% (482/499), and 87% (550/629), respectively. The overall accuracy for the main vessels (left main, left anterior descending, left circumflex, and right coronary arteries) was 93%, 88%, 86%, and 86%, respectively. CONCLUSION CT coronary angiography using a 16-MDCT scanner enables accurate noninvasive detection of significant coronary artery disease in patients hospitalized for acute chest pain syndrome. Furthermore, relative high sensitivity and specificity of CT coronary angiography can be achieved without pharmacologic manipulation of patient heart rates.

Does Transendocardial Injection of Mesenchymal Stem Cells Improve Myocardial Function Locally or Globally? An Analysis From the 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.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. # Novelty and Significance {#article-title-37}

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.

Twinkling Artifact in Gallbladder Adenomyomatosis

Gallbladder adenomyomatosis (GADM) is a common acquired benign hyperplastic disease of the gallbladder mucosa with prevalence of 2.8% to 5%. 1 Sonographically it is characterized by diffuse or focal thickening of the gallbladder wall associated with small intramural cystic spaces, known as Rokitansky-Aschoff sinuses. These sinuses may contain tiny echogenic foci that commonly cause a reverberation artifact. We describe and discuss a case of GADM that on color Doppler sonography showed a twinkling artifact. To the best of our knowledge, this finding has not been described previously.

A new pitfall on abdominal PET/CT: A retained surgical sponge

Positron emission tomography (PET)/computed tomography (CT) and multidetector CT findings of an abdominal retained surgical sponge (RSS) are presented. A PET/CT study performed for evaluation of a suspected abdominal tumor demonstrated the inconclusive finding of a hypometabolic area surrounded by increased 2-[fluorine-18] fluoro-2-deoxy-D-glucose uptake. Follow-up contrast-enhanced multidetector CT suggested the correct diagnosis of an RSS. This is the first known report of the PET/CT appearance of an RSS.

Percutaneous Ultrasonographically Guided Thrombin Injection of Iatrogenic Pseudoaneurysms in Unusual Sites

Objectives. To evaluate the effectiveness and safety of percutaneous ultrasonographically guided thrombin injection as treatment of unusually positioned and unusually large iatrogenic pseudoaneurysms. Methods. Five patients with iatrogenic pseudoaneurysms were evaluated by color duplex ultrasonography. Two patients had additional digital angiography, and 2 had additional computed tomographic angiography. In 3 of the patients, large, painful iatrogenic pseudoaneurysms located proximal (2 patients) and distal (1 patient) to the arteriovenous hemodialysis fistulas had developed, most likely due to erroneous puncture of the arterial side (brachial artery) or venous side (cephalic vein) of the fistulas. An iatrogenic pseudoaneurysm of the anterior tibial artery had developed in the fourth patient after osteotomy of the fibula, and an iatrogenic pseudoaneurysm of the superficial femoral artery had developed in the fifth patient after erroneous puncture during venous transfemoral angiography. With a sterile technique and color duplex ultrasonographic guidance, a diluted solution of bovine thrombin was slowly injected directly into the iatrogenic pseudoaneurysms until cessation of blood flow was seen. Follow‐up color duplex ultrasonography was performed 24 to 48 hours after the ultrasonographically guided thrombin injection. Results. Four iatrogenic pseudoaneurysms were successfully thrombosed during 1 session. Two large iatrogenic pseudoaneurysms necessitated multiple repositions of the injecting needle and several injections of small amounts of thrombin into the residual patent lumen to induce complete thrombosis without an appreciable increase in the total thrombin dosage. Follow‐up examinations revealed complete and persistent thrombosis without evidence of distal embolization. One iatrogenic pseudoaneurysm involving the cephalic vein, distal to an arteriovenous hemodialysis fistula, recurred after apparently successful initial thrombosis. Conclusions. Most iatrogenic pseudoaneurysms are amenable to ultrasonographically guided thrombin injection as long as they are imaged adequately by color duplex ultrasonography.

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

BackgroundTranscatheter 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.MethodsSince 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.ResultsAmong 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.ConclusionThis 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.

Sonographic Evaluation of Vascular Injuries

The purpose of this presentation is to highlight the color Doppler duplex sonographic features of procedure‐related and blunt or penetrating trauma‐related vascular injuries.