Detection of microvascular obstruction (MO) with gadolinium first-pass perfusion (FP) and late gadolinium enhancement (LGE) MRI predicts outcomes of STEMI patients. Previous data indicate the presence of MO early after MI correlates to worse prognosis and left ventricular (LV) remodeling. Nonetheless, FP and early hypoenhancement on LGE may persist after reperfused STEMI for a variable period of time.
Age 76 (65-83) 76 (64-84) 76 (67-82) 0.382 Gender (% Female) 51.6 52.4 49.3 !0.01 Race (% Caocasion) 76.4 74.3 82.0 !0.01 Ishcemic etiology 45.7 45.0 47.7 !0.01 Atrial arrhythomia 30.8 30.0 32.9 !0.01 Pulmonary HTN 6.3 5.3 8.7 !0.01 Renal insufficiency 19.6 19.3 20.4 !0.01 Dyspnea at rest 43.8 42.5 47.1 !0.01 BNP 804 (407-1670) 835 (425-1720) 735 (360-1540) !0.01 Troportin (Abnormal) 21.0 21.4 20.1 !0.01 Discharge beta blocker 67.9 70.2 62.7 !0.01 Discharge ACE-imbioitor 56.0 57.6 52.3 !0.01
Granulocyte‐colony‐stimulating factor (GM‐CSF) is a pleiotropic factor for hematopoiesis that stimulates myeloblasts, monoblasts and mobilization of bone marrow stem cells. Therefore, the GM‐CSF gene is a potential candidate for vessel formation and tissue remodeling in the treatment of ischemic diseases.
A 76-year-old man with a history of coronary bypass graft surgery presented to the Chest Pain Unit with chest discomfort. He underwent myocardial perfusion imaging (MPI) with 99m Tc-sestamibi. Immediately after acquisition of the rest scan he developed a new chest pain episode and received an additional tracer injection. The new images showed hypoperfusion in the inferior and inferolateral walls that were not observed in the previous rest scan images (a arrows). A coronary angiogram revealed subtotal proximal occlusion of a saphenous vein graft to the right coronary artery (b arrow) which was submitted to successful stent implantation. Acute coronary syndrome results from the combination of intermittent thrombotic occlusion and vasoconstriction resulting in markedly decreased regional myocardial perfusion [1]. Abnormal rest MPI in patients with acute chest pain is highly associated with acute myocardial infarction or the need for subsequent coronary revascularization [2]. These images demonstrate the exquisite sensitivity of MPI to changes in rest myocardial perfusion over a short period.
Dementia with Lewy bodies (DLB) is the second most common cause of dementia. The diagnosis of DLB is particularly important because these patients show good response to cholinesterase inhibitors. Clinical and neuroimaging criteria for DLB have not been acceptable for predictive accuracy. We report a case of progressive dementia in which the differentiation of DLB and Alzheimer disease (AD) on the basis of clinical criteria alone was not possible. The patient was admitted to the hospital because he became worse after he had started treatment for severe AD. Both MRI and brain magnetic resonance spectroscopy were normal. The patient underwent myocardial scintigraphy with I-123 MIBG showing marked reduction in cardiac MIBG accumulation. The heart to mediastinum ratio of MIBG uptake was impaired in both early and delayed images. FDG-PET scan before and after activation with a visual attention task showed occipital cortex hypometabolism as compared with AD and a normal control. This case illustrates the value of combining activated brain FDG PET and cardiac MIBG. The association of these 2 techniques could be used as a potential diagnostic tool in a patient with dementia misdiagnosed as AD.
Whether stem cell treatment has the same effect in diabetics and nondiabetics is unknown. To compare outcomes in these two groups, we analyzed data from 26 consecutive patients with chronic ischemic cardiomyopathy who were taking part in two clinical trials. Revascularization was not an option for these patients and they were treated with bone marrow mononuclear cells (BMMNCs). Patients underwent NOGA electromechanical mapping to identify viable myocardium (i.e., with a unipolar voltage >= 6.9 mV), after which they received a mean of 28.5 +/- 4.7x10(6) BMMNCs. Patients were followed up at 6 months. In nondiabetics, there was a significant decrease in end-systolic volume between baseline and 6-month follow-up. In addition, New York Heart Association (NYHA) functional class decreased significantly (P=.04) from 3.0 (1.75-3.0) to 1.0 (1.0-2.0), the Canadian Cardiovascular Society angina score (CCSAS) improved significantly (P=.04) from 3.0 (2.0-4.0) to 1.0 (1.0-1.5), and oxygen uptake increased significantly (P=.04) from 16.4 (13.1-21.5) to 24.5 (17.329.2) ml/kg/min. These changes were not observed in diabetic patients. This is the first clinical study to show that BMMNC injection could have a smaller effect in diabetics.
Se desconoce si la administración de células madre tiene el mismo efecto en pacientes diabéticos y en no diabéticos. Para ello se estudió a 26 pacientes consecutivos, incluidos en dos estudios, tratados con células mononucleadas de médula ósea (CMNMO), con miocardiopatía isquémica crónica y sin opción a revascularización. Se les realizó un mapeo electromecánico con NOGA para identificar miocardio viable (voltaje unipolar ≥ 6,9 mV) y se les inyectó una media de 28,5 ± 4,7 millones de CMNMO. Se realizó un seguimiento a los 6 meses. En los pacientes no diabéticos, se observó una reducción significativa del volumen telesistólico a los 6 meses en comparación con el basal, una disminución significativa de la clase NYHA (de 3 [1,75-3] a 1 [1-2]; p = 0,04), de la puntuación de angina de la clasificación canadiense (de 3 [2-4] a 1 [1-1,5]; p = 0,04) y un aumento del consumo de oxígeno (de 16,4 [13,1-21,5] a 24,5 [17,3-29,2] ml/kg/min; p = 0,04). Estas diferencias no se observaron en los pacientes diabéticos. Éste es el primer estudio clínico que observa que la inyección de CMNMO podría tener un menor efecto en los diabéticos. Whether stem cell treatment has the same effect in diabetics and nondiabetics is unknown. To compare outcomes in these two groups, we analyzed data from 26 consecutive patients with chronic ischemic cardiomyopathy who were taking part in two clinical trials. Revascularization was not an option for these patients and they were treated with bone marrow mononuclear cells (BMMNCs). Patients underwent NOGA electromechanical mapping to identify viable myocardium (i.e., with a unipolar voltage ≥ 6.9 mV), after which they received a mean of 28.5±4.7×106 BMMNCs. Patients were followed up at 6 months. In nondiabetics, there was a significant decrease in endsystolic volume between baseline and 6-month follow-up. In addition, New York Heart Association (NYHA) functional class decreased significantly (P=.04) from 3.0 (1.75-3.0) to 1.0 (1.0-2.0), the Canadian Cardiovascular Society angina score (CCSAS) improved significantly (P=.04) from 3.0 (2.0-4.0) to 1.0 (1.0-1.5), and oxygen uptake increased significantly (P=.04) from 16.4 (13.1-21.5) to 24.5 (17.3- 29.2) ml/kg/min. These changes were not observed in diabetic patients. This is the first clinical study to show that BMMNC injection could have a smaller effect in diabetics.
Purpose: Dinamic behavior of transplanted ABMMC is probably a crucial determinant of its beneficial effects. We aimed to indirectly evaluate cell engraftment of labeled cells and its correlation wi...
A novel, efficient transfection method, based on ultrasound and hydrodynamics, has been developed to transfect heart tissue with plasmid DNA. An ultrasound probe was aimed at the heart of anesthetized rats for 30 sec, at an intensity of 1 MHz and 2 W/cm2. The aorta was clamped and a phosphate-buffered saline (PBS) solution containing pSV-LacZ was quickly injected into the left ventricle. Each animal was maintained in this condition for 20 sec, and then the clamp was opened and the needle was removed. Electrocardiography, performed after 4 weeks, showed mild or no sign of ischemia in all groups. Visual evaluation of heart tissue samples from rats that received 100 microg of pSV-LacZ in 100 microl had only a few blue cells, indicating transfection, and those that received only PBS had no blue cells. However, all heart tissue samples from rats transfected with 100 to 500 microg of pSV-LacZ in 200 microl, or with 200 to 500 microg of pSV-LacZ in 100 micro had many blue cells. The base and epicardium of the heart tissue samples had many more blue cells than did the rest of the samples. Histological results, based on staining with hematoxylin and eosin, showed similar results between control and transfected groups. Therefore, we concluded that gene delivery by plasmid vector in association with ultrasound and hydrodynamics was highly effective in transfecting rat heart.
BACKGROUND:Cardiovascular diseases are the major cause of death in the world. Current treatments have not been able to reverse this scenario, creating the need for the development of new therapies. Cell therapies have emerged as an alternative for cardiac diseases of distinct causes in experimental animal studies and more recently in clinical trials.METHOD/DESIGN:We have designed clinical trials to test for the efficacy of autologous bone marrow derived mononuclear cell therapies in four different cardiopathies: acute and chronic ischemic heart disease, and Chagasic and dilated cardiomyopathy. All trials are multicenter, randomized, double-blind and placebo controlled. In each trial 300 patients will be enrolled and receive optimized therapy for their specific condition. Additionally, half of the patients will receive the autologous bone marrow cells while the other half will receive placebo (saline with 5% autologous serum). For each trial there are specific inclusion and exclusion criteria and the method for cell delivery is intramyocardial for the chronic ischemic heart disease and intracoronary for all others. Primary endpoint for all studies will be the difference in ejection fraction (determined by Simpson's rule) six and twelve months after intervention in relation to the basal ejection fraction. The main hypothesis of this study is that the patients who receive the autologous bone-marrow stem cell implant will have after a 6 month follow-up a mean increase of 5% in absolute left ventricular ejection fraction in comparison with the control group.DISCUSSION:Many phase I clinical trials using cell therapy for cardiac diseases have already been performed. The few randomized studies have yielded conflicting results, rendering necessary larger well controlled trials to test for efficacy of cell therapies in cardiopathies. The trials registration numbers at the NIH registry are the following: Chagasic cardiomyopathy (NCT00349271), dilated cardiomyopathy (NCT00333827), acute myocardial infarction (NCT00350766) and Chronic Ischemic Heart Disease (NCT00362388).
We describe cell therapy for severe ischemic heart failure using transendocardial injection of autologous bone-marrow-derived mononuclear cells. The treated patients had significantly less heart failure and angina, sustained significant improvement of pumping power, exercise capacity, cardiac muscle irrigation, and blood supply to the body. Electrical and mechanical mappings of the myocardium before and after the therapy, and anatomopathological examination of the myocardium of one of the patients that had deceased of a stroke eleven months after the treatment indicated sustained neoangiogenesis and improvement of activity and quantity of cardiomyocytes in the injected regions. Post-hoc analyses of injected cell phenotype and improvement of myocardial function indicate that presence of CD8+ and CD56+ cells does not correlate with good prognostics, suggesting a possibility of cell selection. For 'no-option' severe cardiac patients, significant benefits of cell therapy and absence of adverse effects may justify the application of bone-marrow-derived cell therapy.
Objective: To evaluate the feasibility of monitoring the autologous mononuclear bone marrow (ABMMN) cells implanted into the brain after acute ischemic stroke by the technique of labeling with Tc-99m-HMPAO. Case Report: A 37-year-old man presented with aphasia, right-side hypoesthesia, and right homonymous hemianopsia after an acute ischemic stroke of the left middle cerebral artery. He was included in an autologous bone marrow mononuclear cell-based therapy research protocol about the safety of intra-arterial autologous bone marrow mononuclear cell transplantation for acute ischemic stroke. Nine days after the stroke he received 3.0 × 107 ABMMN cells delivered into the left cerebral middle artery via a balloon catheter. Approximately 1% of these cells were labeled with 150 MBq (4 mCi) Tc-99m by incubation with hexamethylpropylene amine oxime (HMPAO). Results: Brain perfusion images with Tc-99m ECD demonstrated hypoperfusion in the left temporal and parietal regions. The perfusion brain images were compared with tomographic views of the brain obtained 8 hours after ABMMN-labeled cell delivery, revealing intense accumulation of the ABMMN-labeled cells in the ipsilateral hemisphere. A whole-body scan was done and showed left brain, liver, and spleen uptake. Conclusions: Our results showed that Tc-99m HMPAO can be used to label ABMMN cells for in vivo cell visualization, and that brain SPECT imaging with labeled ABMMN cells is a feasible noninvasive method for studying the fate of transplanted cells in vivo. Additionally, our findings demonstrate the localization of these intra-arterially injected cells.
Objectives: Evaluate the clinical manifestations, dysfunction and ventricular remodeling degree and hystologicals alterations of the patients with viral miocarditis (VMc) and non viral (NVMc). Methods: 60 patients with miocarditis (Mc) diagnosis, proved by histological analyses by Hematoxilin Eosine (HE) and by imunohystoquimical (IH) for HLADR. Was realized viral research by PCR/NestedPCR for? Adenovirus, Enterovirus, Parvovirus B19, ECHO, and HCV. The patients were evaluated clinically, by echocardiogram, Cardiac Magnetic Resonance with Gadolineum (CMR). Were realized the Mann-Whitney Test for medias comparison and Qui-Quadrado for proporcion evaluation. Results: 18 patients presented VMc and 42 patients NVMc. No difference was observed between the groups about gender (p = 0.37), HF clinic (p = 0.6), clinical apresentation of congestive HF and Left Heart Failure (p = 0.6), HF functional class (p = 0.92) and beginning of HF < 6 months (77% vs 65%, p = 0.23). The patients with NVMc presented younger (36y vs 51 y, p = 0.04), and no difference about syntoms: angina (17% vs 23%, p = 0.69), palpitation (22%vs 25%, p = 0.8), and grippe (45% vs 26%, p = 0.2). There was no difference between the groups about LVEF (26% vs 30%, p = 0.73), and chambers diameters: left ventricular end diastolic diameter (LVEDD) (p = 0.25), left ventricular end systolic diameter(LVESD)(p = 0.48). No difference about LBBB (p = 0.86) and alterations of ventricular repolarization (p = 0.8). No difference on positive MR between the groups (70% vs 61%, p = 0.48). At histological analyses, there was no difference about myocitolisis presence (78% vs 70%, p = 0.53), and intersticial collagen percentual (13% vs 9%, p = 0.75). At IH there was no difference about intersticial HLADR percentual (1.1% vs 1.6%, p = 0.75). Conclusion: 1)The clinical manifestations did not allow to distinguish a VMc of NVMc. The NVMc patients were younger. 2) Both Mc presented the same disfunction and remodeling degree. 3) Both Mc presented similar manifestation at ECG 4) The capacity of Mc detection by MR with gadollineum was similar in both MC forms. 5) The hystological alterations of inflammation and miocitolisis are similar in both Mc groups.