Acute myocardial infarction reparation/regeneration strategy using Wharton's jelly multipotent stem cells as an 'unlimited' therapeutic agent: 3-year outcomes in a pilot cohort of the CIRCULATE-AMI trial.

Introduction: CIRCULATE-AMI (NCT03404063), a cardiac magnetic resonance imaging (cMRI) infarct size-reduction-powered double-blind randomized controlled trial (RCT) of standardized Wharton jelly multipotent stem cells (WJMSCs, CardioCell Investigational Medical Product) vs. placebo (2 : 1) transcoronary transfer on acute myocardial infarction (AMI) day ~5-7, is preceded by safety and feasibility evaluation in a pilot study cohort (CIRCULATE-AMI PSC). Aim: To evaluate WJMSC transplantation safety and evolution of left ventricular (LV) remodeling in CIRCULATE-AMI PSC. Material and methods: In 10 consecutive patients (32-65 years, peak CK-MB 533 ±89 U/l, cMRI-LVEF 40.3 ±2.7%, cMRI-infarct size 20.1 ±2.8%), 30 × 106 WJMSCs were administered using a novel cell delivery-dedicated, coronary-non-occlusive method (CIRCULATE catheter). Other treatment was guideline-based. Results: WJMSC transfer was safe and occurred in the absence of coronary (TIMI-3 in all) or myocardial (corrected TIMI frame count (cTFC) 45 ±8 vs. 44 ±9, p = 0.51) flow deterioration or troponin elevation. By 3 years, 1 patient died from a new, non-index territory AMI; there were no other major adverse cardiovascular and cerebrovascular events (MACCE) and no adverse events that might be related to WJMSCs. cMRI infarct size was reduced from 33.2 ±7.6 g to 25.5 ±6.4 g at 1 year and 23.1 ±5.6 g at 3 years (p = 0.03 vs. baseline). cMRI, SPECT, and echo showed a consistent, statistically significant increase in LVEF at 6-12 months (41.9 ±2.6% vs. 51.0 ±3.3%, 36.0 ±3.9% vs. 44.9 ±5.0%, and 38.4 ±2.5% vs. 48.0 ±2.1% respectively, p < 0.01 for all); the effect was sustained at 3 years. Conclusions: CIRCULATE-AMI PSC data suggest that WJMSC transcoronary application ~5-7 days after large AMI in humans is feasible and safe and it may be associated with a durable LVEF improvement. CIRCULATE-AMI RCT will quantify the magnitude of LV adverse remodeling attenuation with CardioCell/placebo administration.

Diffusion-tensor magnetic resonance imaging of the human heart in health and in acute myocardial infarction using diffusion-weighted echo-planar imaging technique with spin-echo signals.

Introduction: Originally thought unsuitable due to proneness to myocardial motion and susceptibility artefacts, spin-echo echo planar imaging (SE-EPI) has gained attention for the cardiac diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) offering higher SNR and lower achievable echo time (TE). Aim: The application of DTI for patients with acute myocardial infarction (AMI) using our methodology developed on the basis of the SE-EPI sequence. Material and methods: Twelve patients with AMI and six healthy controls were enrolled in the preliminary DTI study within the CIRCULATE STRATEGMED 2 project. Our method relied on a pilot ECG-triggered DTI examination, based on which the initial evaluation was possible and allowed proper manipulation of TE (64/47 ms for patients/control), repetition time (TR) and ECG trigger delay in the consecutive DTI. Results: The study demonstrated that by using our algorithm it was possible to obtain DWI images showing infarct zones identified on T1-weighted images with late gadolinium-enhancement (LGE) with division into subtle and severe damage. Quantitative DTI showed increased mean diffusivity (MD) and decreased fractional anisotropy (FA) in the infarct compared to remote tissue. The application of B-matrix spatial distribution (BSD) calibration allowed the improvement of FA. Conclusions: Our algorithm is suitable for qualitative assessment of infarction zones with different severity. The analysis of the quantitative DTI showed that despite the lack of motion compensation blocks in the applied SE-EPI sequence, it was possible to approach the diffusion tensor parameter values reported for the myocardium.

Lack of Relationship between Fibrosis-Related Biomarkers and Cardiac Magnetic Resonance-Assessed Replacement and Interstitial Fibrosis in Dilated Cardiomyopathy.

The relationship between circulating fibrosis-related molecules and magnetic resonance-assessed cardiac fibrosis in dilated cardiomyopathy (DCM) is poorly understood. To compare circulating biomarkers between DCM patients with high and low fibrosis burdens, we performed a prospective, single-center, observational study. The study population was composed of 100 DCM patients (87 male, mean age 45.2 ± 11.8 years, mean ejection fraction 29.7% ± 10.1%). Replacement fibrosis was quantified by means of late gadolinium enhancement (LGE), whereas interstitial fibrosis was assessed via extracellular volume (ECV). Plasma concentrations of cardiotrophin-1, growth differentiation factor-15, platelet-derived growth factor, procollagen I C-terminal propeptide, procollagen III N-terminal propeptide, and C-terminal telopeptide of type I collagen were measured. There were 44% patients with LGE and the median ECV was 27.7%. None of analyzed fibrosis serum biomarkers were associated with the LGE or ECV, whereas NT-proBNP was independently associated with both LGE and ECV, and troponin T was associated with ECV. None of the circulating fibrosis markers differentiated between DCM patients with and without replacement fibrosis, or patients stratified according to median ECV. However, cardiac-specific markers, such as NT-proBNP and hs-TnT, were associated with fibrosis. Levels of circulating markers of fibrosis seem to have no utility in the diagnosis and monitoring of cardiac fibrosis in DCM.

Diffusion as a Natural Contrast in MR Imaging of Peripheral Artery Disease (PAD) Tissue Changes. A Case Study of the Clinical Application of DTI for a Patient with Chronic Calf Muscles Ischemia.

This paper reports a first application of diffusion tensor imaging with corrections by using the B-matrix spatial distribution method (BSD-DTI) for peripheral artery disease (PAD) detected in the changes of diffusion tensor parameters (DTPs). A 76-year-old male was diagnosed as having PAD, since he demonstrated in angiographic images of lower legs severe arterial stenosis and the presence of lateral and peripheral circulation and assigned to the double-blind RCT using mesenchymal stem cells (MSCs) or placebo for the regenerative treatment of implications of ischemic diseases. In order to indicate changes in diffusivity in calf muscles in comparison to a healthy control, a DTI methodology was developed. The main advantage of the applied protocol was decreased scanning time, which was achieved by reducing b-value and number of scans (to 1), while maintaining minimal number of diffusion gradient directions and high resolution. This was possible due to calibration via the BSD method, which reduced systematic errors and allowed quantitative analysis. In the course of PAD, diffusivities were elevated across the calf muscles in posterior compartment and lost their anisotropy. Different character was noticed for anterior compartment, in which diffusivities along and across muscles were decreased without a significant loss of anisotropy. After the intervention involving a series of injections, the improvement of DTPs and tractography was visible, but can be assigned neither to MSCs nor placebo before unblinding.

CT evaluation of aberrant right subclavian artery: anatomy and clinical implications.

PurposeThe aim of the study was to perform CT angiography-based evaluation of aberrant right subclavian artery prevalence, anatomy, and its influence on clinical symptoms. METHODS: A total of 6833 patients who underwent 64-slice or dual-source CT angiography and those who revealed aberrant right subclavian artery underwent evaluation of its anatomy and were interviewed for the presence of clinical symptoms. RESULTS: Aberrant right subclavian artery was found in 32 (0.47%) patients consisting of 13 males and 19 females, with mean age of 60.8±13.4 years. Among the interviewed 30 (94%) patients, oesophageal compression was observed in 14 cases (47%) and tracheal compression in three cases (10%). None of the patients underwent surgery related to aberrant right subclavian artery. Dysphagia was the most common clinical symptom in nine cases (30%), and in those patients the median distance between aberrant right subclavian artery and trachea was lower (4 mm) than in individuals without dysphagia (7.5 mm) (p = 0.009). The median lumen area of the aberrant right subclavian artery at the level of oesophagus was higher in patients with dysphagia (208 mm2) compared with individuals without dysphagia (108 mm2) (p = 0.01). CONCLUSIONS: Aberrant right subclavian artery is a rare occurring abnormality in CT angiography. In the evaluated adult population, the most common symptom was dysphagia, which occurred in patients with decreased distance between aberrant right subclavian artery and trachea and increased lumen area of the aberrant artery at the level of compressed oesophagus.

Applications of low-cost 3D printing in left atrial appendage closure using epicardial approaches - initial clinical experience.

INTRODUCTION: Left atrial appendage occlusion procedure (LAAO) became an alternative method for stroke prevention in atrial fibrillation (AF) patients with contraindication or intolerance for oral anticoagulation therapy. However, LAA anatomy is complex with several different types of LAA morphology. Therefore matching the correct size of a delivery device to LAA morphology is difficult. In such circumstances, the 3D-printed model of LAA closure may be useful for preoperative planning which increases the efficacy of LAAO procedure. MATERIAL AND METHODS: We report as a first 2 cases of LAA occlusion procedure using 2 different systems: thoracoscopic AtriClip and the LARIAT device in which a 3D printed LAA model was used in preoperative planning. RESULTS: In the first patient, preoperative measurements of 3D LAA model were performed using a dedicated selection guide for AtriClip device were comparable with the intraoperative examination. Left atrial appendage was closed epicardial using 40 mm size AtriClip. In second patients, LAA closure was performed completely percutaneously using LARIAT device. For better visualization of LAA shape on fluoroscopy and TEE examination, intraoperatively sterilized 3D LAA model was used during the procedure. In both cases, intraoperative TEE examination confirmed complete LAA closure with no leak. CONCLUSIONS: Left atrial appendage 3D model is a useful tool in preoperative planning of a left atrial appendage occlusion using epicardial approaches with thoracoscopic or percutaneous access using LARIAT device. The quality of low-cost 3D printed LAA model is sufficient in planning minimally invasive procedure.

Magnetic resonance imaging and clinical outcome in patients with symptomatic carotid artery stenosis after carotid artery revascularization.

INTRODUCTION: About 30% of patients with carotid artery stenosis (CAS) develop dementia after a cerebral ischemic event (CIE), and 20-50% suffer from CIE recurrence during 6 months. Carotid artery revascularization (CAR) may prevent CIE recurrence, at the cost of new microembolic lesions (MES). The impact of CAR on cognitive function is debatable. AIM: To assess functional and cognitive outcome, cerebral flow on transcranial Doppler (TCD) and brain magnetic resonance imaging (MRI) in patients with symptomatic CAS referred for CAR. MATERIAL AND METHODS: Twenty-two patients (aged 69.0 ±7.2 y.o., 15 male) with recent CIE (21.9 ±20.9 days to CAR) related to CAS of mean 89.8 ±3.9% lumen reduction were prospectively evaluated with TCD, diffusion and perfusion MRI, Montreal Cognitive Assessment (MoCA), Mini Mental State Examination (MMSE), modified Rankin Scale (mRS) and the National Institutes of Health Stroke Scale (NIHSS) 24 h before, at 24-48 h and 1 month following CAR. RESULTS: New MES were found in 11 (50%) subjects following CAR. CAR resulted in a significant increase of cerebral flow velocity in the middle and anterior cerebral arteries (p < 0.002 and p = 0.003; respectively) and cerebral perfusion measured by time to peak (TTP) and mean transit time (MTT) (p = 0.0009 and p = 0.0002; respectively). Neurologic tests showed improvement in NIHSS (2.4 ±1.6 to 1.5 ±1.2, p = 0.003), mRS (from 1.3 ±0.9 to 0.7 ±0.9, p = 0.005), and MMSE (26.7 ±2.2 to 27.6 ±2.3, p = 0.019) at 1 month, while similar MoCA scores were observed before and 1 month after CAR (23.4 ±3.3 vs. 24.1 ±3.7, p = 0.136). CONCLUSIONS: Improvement of cerebral flow and perfusion and functional outcome, as well as at least no cognitive decline, is observed after CAR for symptomatic CAS.

Anomalous origin of the coronary artery from the wrong coronary sinus evaluated with computed tomography: "high-risk" anatomy and its clinical relevance.

OBJECTIVE: The aim of the study was to assess coronary arteries arising from the wrong coronary sinus, including CT-evaluated high-risk anatomic features, clinical symptoms and cardiac events during follow-up. METHODS: A total of 7,115 patients scheduled for 64-slice or dual-source cardiac CT were screened for the presence of isolated anomalous origin of the coronary artery from the wrong coronary sinus. RESULTS: Anomalous origin of the coronary artery was found in 54 (0.76 %) patients (29 men, 25 women, mean age 60.9 ± 11.6 years). Sixteen (30 %) patients with abnormal right coronary origin (ARCA) more commonly had a slit-like orifice (15 vs. 3; p < 0.001), intramural course (15 vs. 3; p < 0.001) and interarterial course (11 vs. 0; p < 0.001) than 22 (41 %) and 13 (24 %) individuals with abnormal circumflex artery (ALCx) and left coronary artery (ALCA) origin, respectively. Patients with ALCA presented less frequently with chest pain than subjects with ARCA and ALCx (25 vs. 3; p = 0.03). Patients with ARCA tended to show higher occurrence of cardiac events in the follow-up than individuals with ALCA and ALCx (5 vs. 4; p = NS). CONCLUSIONS: High-risk anatomy features are most common in patients with ARCA and these patients also have higher prevalence of chest pain and cardiac events in the follow-up than individuals with ALCA and ALCx. KEY POINTS: • Multislice computed tomography enables detection and evaluation of the coronary artery anomalies. • Anomalous anatomy of the coronary artery potentially influences the prevalence of adverse events. • Adverse events tend to be most common in anomalous right coronary arteries.

[Cystic lesion in the topography of occluded aortocoronary saphenous vein bypass]. / Zmiana torbielowata w topografii niedroinego, zylnego pomostu aortalno-wiencowego.

Article presents a case of a 66-year old manwith a pericardial cyst, localized in tlhe topography of an occluded aorto-ccoronary saphenous vein graft. The lesion was revealed in computed tomogrnaphy and also evaluated in the subsequently performed magnetic resonance.

[Anomalous right upper pulmonary venous drainage into the superior vena cava with coexistence sinus venosus atrial septal defect (ASD)]. / Nieprawidlowy splyw zyly plucnej górnej prawej do zyly glównej górnej wraz ze wspólistniejacym ubytkiem w przegrodzie miedzyprzedsionkowej o typie zatoki zylnej (ASD).

Article presents a case of a 71-year old woman with pulmonary right upper venous drainage into the superior vena cava and with coexistence sinus venous type Atrial Septal Defect (ASD) which was revealed as interesting finding in multislices computed tomography angiography during estimation of coronary arteries.

[Right corbnary artery aneurysms in patient with suspicion of heart tumor]. / Tetniaki prawej tetnicy wiencowej u pacjenta z podejrzeniem guza serca.

Coronary arteries aneurysms are rare occurring abnormalities, concerning mostly right coronary artery. We present a case of a 60-year old man who underwent magnetic resonance (MRI) due to suspicion of cardiac tumor in the previously performed echocardiography. MRI examination suggested right coronary artery aneurysm. The diagnosis was confirmed in the performed computed tomography (CT) and additionally coronary aneurysm of distal part of right coronary artery was visualized.

Does magnetic resonance spectroscopy identify patients with minimal hepatic encephalopathy?

BACKGROUND AND PURPOSE: The results of a few studies suggest that magnetic resonance spectroscopy of the brain could allow detection of minimal hepatic encephalopathy. The goal of this study was to assess the ability of magnetic resonance spectroscopy to differentiate between cirrhotic patients with and without minimal hepatic encephalopathy. MATERIAL AND METHODS: Localized magnetic resonance spectroscopy was performed in the basal ganglia, occipital gray matter and frontal white matter in 46 patients with liver cirrhosis without overt encephalopathy and in 45 controls. Neurological and neuropsychological examination was performed in each participant. RESULTS: The patients with liver cirrhosis had a decreased ratio of myoinositol to creatine in occipital gray matter and frontal white matter (mean: 0.17 ± 0.05 vs. 0.20 ± 0.04, p = 0.01 and 0.15 ± 0.05 vs. 0.19 ± 0.04, p < 0.01, respectively) and a decreased ratio of choline to creatine in occipital gray matter (mean: 0.32 ± 0.07 vs. 0.36 ± 0.08, p = 0.03). Minimal hepatic encephalopathy was diagnosed in 7 patients. Metabolite ratios did not differ significantly between patients with and without minimal hepatic encephalopathy. Metabolite ratios did not differ significantly between patients with Child-Pugh A and those with Child-Pugh B. CONCLUSIONS: Magnetic resonance spectroscopy does not allow accurate diagnosis of minimal hepatic encephalopathy. A similar profile of metabolites in the brain is observed in cirrhotic patients without cognitive impairment.

Computed tomography coronary angiography and invasive coronary angiography demonstrate high correlation for area stenosis quantification in noncalcified and mixed plaques.

We compared the variance of area and diameter significant stenosis measurement between quantitative computed tomography coronary angiography (QCTA) and quantitative invasive coronary angiography (QCA). Fifty patients presenting 65 significant coronary artery stenoses (≥70% area stenosis) in QCTA and QCA were included. Spearman's rank correlation revealed that area stenosis measurement by QCTA and QCA yields higher correlation than diameter stenosis and is highest for noncalcified and mixed lesions.

Osteoprotegerin, but not osteopontin, as a potential predictor of vascular calcification in normotensive subjects.

We conducted a cross-sectional observation study that included 500 asymptomatic subjects to investigate the relationship between bone metabolism and coronary artery calcification (CAC) in hypertensive conditions. Osteoprotegerin (OPG) and osteopontin (OPN) levels and their associations with hypertension were analyzed to predict CAC in 316 subjects. Multislice computed tomography was used to quantify CAC. Multivariate analysis of variance was used to test the non-interactive effects of hypertension, CAC severity and biomarker levels, and the logistic regression model was applied to predict the risk of CAC. OPG and OPN concentrations were significantly higher in the hypertensive than the normotensive subjects, at 3.0 (2.3-4.0) pmol l(-1) and 51 (21-136) ng ml(-1) vs. 2.4 (2.0-3.0) pmol l(-1) and 41 (13-63) ng ml(-1), respectively. The OPG level, but not OPN level, increased with age (r = 0.29; P = 0.0001). Zero or minimal CAC (<10 Agatston units (AU)) was observed in 63% of the subjects, mild (11-100 AU) in 17%, moderate (101-400 AU) in 12% and severe (401-1000 AU)-to-extensive (>1000 AU) in 8%. In hypertensive subjects, only glomerular filtration rate (GFR) (ß = -0.67) and gender (ß = 0.52) were significant predictors for CAC (R = 0.68). In normotensive patients, GFR (ß = -0.81), gender (ß = 0.48) and log-transformed OPG levels (ß = 0.15) were significant predictors for CAC. OPG levels were associated with an increased risk of CAC in normotensive subjects only (odds ratio: 3.37; 95% confidence interval (1.63-6.57); P = 0.0002). OPG predicted a premature state of vascular calcification in asymptomatic normotensive individuals, and renal function significantly contributed to this process in both hypertensive and normotensive subjects.

The composition and extent of coronary artery plaque detected by multislice computed tomographic angiography provides incremental prognostic value in patients with suspected coronary artery disease.

Multislice computed tomographic coronary angiography (CTCA) provides accurate noninvasive assessment of coronary artery disease (CAD). However, data on the prognostic value of CTCA in patients with suspected CAD are only beginning to emerge. The aim of the study was to assess the prognostic value of CTCA in patients with suspected CAD. Patients (males = 259, females = 235; mean age 58.2 ± 9.8 years) with suspected CAD who underwent 16- or 64-slice CTCA were followed for 1,308 ± 318 days for cardiac death, nonfatal myocaridal infarction (MI) and late (>90 days after CTCA) revascularization. Patient outcomes were related to clinical and CTCA data. Cox proportional-hazards model was applied in stepwise forward fashion to identify outcome predictors. Coronary artery plaque was found in 340 patients. Cardiac events occurred in 40 patients including cardiac death (n = 9), nonfatal MI (n = 8) and late revascularization (n = 23). A multivariable analysis identified the following independent predictors for adverse cardiac events: obstructive plaque in a proximal coronary artery segment (hazard ratio (HR) 2.73; 95% confidence interval (CI): 1.35-5.54; P = 0.005), the number of segments with noncalcified plaque(s) (HR 1.53 per segment; 95%CI: 1.21-1.92; P < 0.001), the number of segments with mixed plaque(s) (HR 1.56 per segment; 95%CI: 1.27-1.92; P < 0.001) and the number of segments with calcified plaque(s) (HR 1.21 per segment; 95%CI: 1.07-1.37; P = 0.002). In patients with suspected CAD, both the extent and composition of atherosclerotic plaque as determined by CTCA are prognostic of subsequent cardiac events.