Factors associated with degraded trabecular bone score in heart transplant recipients.

Trabecular bone score (TBS) is a textural index that provides indirect evaluation of trabecular microarchitecture. It improves fracture risk assessment in several high-risk populations. We aimed to evaluate the role of TBS assessment in heart transplant recipients (HTR). In a cross-sectional study with 87 HTR (69 males and 18 females), we assessed TBS and evaluated potential associations between TBS and factors related to increased fracture risk. We also evaluated the correlations between the presence of vertebral fractures (VF) and degraded TBS. We confirmed degraded TBS in the majority of HTR. 27.6% of HTR had partially degraded, 27.6% had degraded TBS. HTR with degraded TBS were older, had higher body mass index, lower bone mineral density (BMD), and T-score. As opposed to stable BMD over different time points, TBS significantly differed among different post-transplant time periods. TBS did not correlate with current methylprednisolone or past zoledronic acid treatment, presence of hypogonadism or diabetes. TBS did not have additional value over BMD in predicting the presence of VF. Most fractures occurred in patients with osteopenia and in patients with partly degraded TBS. Studies with longitudinal designs and larger sample sizes are warranted to further assess the potential role of TBS in HRT.

Effects of Repetitive Transendocardial CD34+ Cell Transplantation in Patients With Nonischemic Dilated Cardiomyopathy.

RATIONALE: Preclinical data in heart failure models suggest that repetitive stem cell therapy may be superior to single-dose cell administration. OBJECTIVE: We investigated whether repetitive administration of CD34+ cells is superior to single-dose administration in patients with nonischemic dilated cardiomyopathy. METHODS AND RESULTS: Of 66 patients with dilated cardiomyopathy, New York Heart Association functional class III, and left ventricular ejection fraction (LVEF) <40% enrolled in the study, 60 were randomly allocated to repetitive cell therapy (group A, n=30) or single-cell therapy (group B, n=30). Patients received G-CSF (granulocyte colony-stimulating factor) for 5 days, and 80 million CD34+ cells were collected by apheresis and injected transendocardially. In group A, cell therapy was repeated at 6 months. All patients were followed for 1 year, and the primary end point was the difference in change in LVEF between the groups. At baseline, the groups did not differ in age, sex, LVEF, NT-proBNP (N-terminal pro-B-type natriuretic peptide), or 6-minute walk test distance. When directly comparing groups A and B at 1 year, there was no significant difference in change in LVEF (from 32.2±9.3% to 41.2±6.5% in group A and from 30.0±7.0% to 37.9±5.3% in group B, P=0.40). From baseline to 6 months, both groups improved in LVEF (+6.9±3.3% in group A, P=0.001 and +7.1±3.5% in group B, P=0.001), NT-proBNP (-578±211 pg/mL, P=0.02 and -633±305 pg/mL, P=0.01), and 6-minute walk test (+87±21 m, P=0.03 and +92±25 m, P=0.02). In contrast, we observed no significant changes between 6 months and 1 year (LVEF: +2.1±2.3% in group A, P=0.19 and +0.8±3.1% in group B, P=0.56; NT-proBNP: -215±125 pg/mL, P=0.26 and -33±205 pg/mL, P=0.77; 6-minute walk test: +27±11 m, P=0.2 and +12±18 m, P=0.42). CONCLUSIONS: In patients with dilated cardiomyopathy, repetitive CD34+ cell administration does not seem to be associated with superior improvements in LVEF, NT-proBNP, or 6-minute walk test when compared with single-dose cell therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02248532.

Levosimendan Efficacy and Safety: 20 Years of SIMDAX in Clinical Use.

Levosimendan was first approved for clinical use in 2000, when authorization was granted by Swedish regulatory authorities for the hemodynamic stabilization of patients with acutely decompensated chronic heart failure (HF). In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitization and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced HF, right ventricular failure, pulmonary hypertension, cardiac surgery, critical care, and emergency medicine. Levosimendan is currently in active clinical evaluation in the United States. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and noncardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, the United Kingdom, and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute HF arena in recent times and charts a possible development trajectory for the next 20 years.

Endocrine disorders after heart transplantation: national cohort study.

BACKGROUND: Endocrine disorders in patients after heart transplantation (HT) remain understudied. We aimed to assess endocrine profiles and management of HT recipients in the early post- transplant period. METHODS: We conducted a retrospective cohort study on 123 consecutive HT recipients in the Advanced Heart Failure and Transplantation Programme between 2009 and 2018. All recipients had per-protocol endocrine follow-up within the first postoperative year. The median time to first post-transplant endocrine follow-up was 3 months (IQR 2-4). We assessed the incidence of vitamin D deficiency, bone mineral density, history of low energy fractures, hypogonadism in male recipients, posttransplant diabetes mellitus, and thyroid and parathyroid function. RESULTS: We enrolled 22 women and 101 men of median age 57 years (IQR 50-63). Post-transplant diabetes mellitus developed in 14 patients (11.4%). 18 of 25 patients (14.6%) with preexisting type 2 diabetes mellitus required intensification of antidiabetic therapy. 38 male patients (40.4%) had hypogonadism. 5 patients (4.6%) were hypothyroid and 10 (9.3%) latent hyperthyroid. Secondary hyperparathyroidism was present in 19 (17.3%), 25-hydroxyvitamin D deficiency in 64 (54.7%) of patients. Osteoporosis was present in 26 (21.1%), osteopenia in 59 (48.0%) patients. 47 vertebral fractures, 3 hip and 1 humerus fractures occurred in 21 patients. Most of the patients had coincidence of two or three disorders, while less than 5% did not have any endocrine irregularities. All patients received calcium and vitamin D supplements. Forty-six patients (37.4%) were treated with zoledronic acid, 12 (9.8%) with oral bisphosphonates. Two patients were treated with teriparatide. CONCLUSIONS: The prevalence of multiple endocrine disorders early after heart transplantation is high. Assessment and management of increased fracture risk and all other potentially affected endocrine axes should be considered as a standard of care in this early period.

Stem Cell Therapy for Chronic and Advanced Heart Failure.

PURPOSE OF REVIEW: The purpose of this review is to discuss recent advances in the field of cell therapy in patients with heart failure with reduced ejection fraction (HFrEF) of ischemic (iCMP) and nonischemic (dCMP) etiology, heart failure with preserved ejection fraction (HFpEF), and in advanced heart failure patients undergoing mechanical circulatory support (LVAD). RECENT FINDINGS: In HFrEF patients (iCMP and dCMP cohorts), autologous and/or allogeneic cell therapy was shown to improve myocardial performance, patients' functional capacity, and neurohumoral activation. In HFpEF patient population, the concept of cell therapy in novel and remains largely unexplored. However, initial data are very encouraging and suggest at least a similar benefit in improvements of myocardial performance (also diastolic function of the left ventricle), exercise capacity, and neurohumoral activation. Recently, cell therapy was explored in the sickest population of advanced heart failure patients undergoing LVAD support also showing a potential benefit in promoting myocardial reverse remodeling and recovery. In the past decade, several cell therapy-based clinical trials showed promising results in various chronic and advanced heart failure patient cohorts. Future cell treatment strategies should aim for more personalized therapeutic approaches by defining optimal stem cell type or their combination, dose, and delivery method for an individual patient adjusted for patient's age and stage/duration of heart failure.

Electroanatomic Properties of the Myocardium Predict Response to CD34+ Cell Therapy in Patients With Ischemic and Nonischemic Heart Failure.

BACKGROUND: We investigated a correlation between electromechanical properties of the myocardium and response to CD34+ cell therapy in patients with chronic heart failure. METHODS AND RESULTS: We enrolled 40 patients with ischemic cardiomyopathy (ICM) and 40 with nonischemic dilated cardiomyopathy (DCM). All patients were in New York Heart Association functional class III and had a left ventricular ejection fraction (LVEF) <40%. CD34+ cells were mobilized by granulocyte colony-stimulating factor and collected via apheresis. Electroanatomic mapping was performed to define areas of myocardial scar and hibernation, and CD34+ cells were injected transendocardially in the hibernating areas. Patient were followed for 6 months; responders were defined as patients with LVEF increase of >5%. At baseline, the groups did not differ in sex, LVEF, creatinine, N-terminal pro-B-type natriuretic peptide or electroanatomic parameters (scar area: 53 ± 18% in ICM vs 55 ± 23% in DCM [P = .83]; hibernating area: 23 ± 13% vs 22 ± 12% [P = .56]). At 6 months we found similar rates of responders in both groups (60% in ICM vs 65% in DCM [P = .95]). When compared with nonresponders, responders had less myocardial scar (47 ± 17% vs 58 ± 15% [P = .003]). CONCLUSIONS: In patients with chronic heart failure due to ICM and DCM we observed similar electroanatomic properties of the myocardium. In both groups, lower myocardial scar burden was associated with better clinical response to CD34+ cell therapy.

Low serum testosterone is associated with impaired graft function early after heart transplantation.

BACKGROUND: We sought to investigate a correlation between serum testosterone levels and graft function early after heart transplantation. METHODS: In a cross-sectional study, we measured serum testosterone levels 4 weeks after heart transplantation in 49 consecutive male recipients. Echocardiography was carried out to evaluate graft function. Low serum testosterone was defined as <11 nmol/L. RESULTS: Low serum testosterone was present in 21 (43%) recipients (Group A), and 28 (57%) had normal testosterone levels (Group B). The two groups did not differ in age and presence of renal dysfunction, arterial hypertension, diabetes, or hyperlipidemia. Donor age and allograft ischemic time were not different between the two groups. Both groups had comparable tacrolimus through levels, dose of mycophenolate mophetil, and methylprednisolone. Patients in Group A had significantly lower LVEF (58±5% vs 65±6% vs Group B, P=.001) and TAPSE (1.3±0.3 cm vs 1.6±0.3 cm in Group B, P=.01). In comparison with Group B, more patients in Group A were found to have low grade (1R) rejection (25% vs 3%; P=.02). CONCLUSION: Low serum testosterone levels appear to be associated with impaired graft function and an increased incidence of low-grade rejection episodes early after heart transplantation.

Assessment of stability of CD34+ cell products enriched by immunoselection from peripheral blood mononuclear cells during refrigerated storage.

Durable engraftment of transplanted CD34+ cells largely depends on the quality of the cell product. Limited data are currently available about extended storage of immunoselected CD34+ cells. The aim of our study was to assess the stability of CD34+ cell product with the cells stored in high concentration (80×106 in 6mL) in small bags intended for cell implantation. Cell products were prepared by leukapheresis and immunoselection (Clinimacsplus procedure) from 13 patients with chronic dilated cardiomyopathy. CD34+ cell products were stored at 2-8°C and analyzed at time 0 (fresh products), 24, 48h, 4 and 6 days. Product viability, absolute number of viable CD34+ cells and apoptosis were determined by flow cytometry. Microbiological contamination of the cell products was tested by BACTEC system. The mean viability of CD34+ cells decreased by 2.7% within 24h, by 13.4% within 48h and by 37.5% within 6 days. The mean recovery of viable CD34+ cells was 91.1%, 74.8%, 66.3% and 56.2% at 24, 48h, 4 and 6 days, respectively. The mean fraction of early apoptotic cells in fresh and stored products was 4.9±3.5% at 0h, 5.9±3.8% at 24h, 4.2±3.1% at 48h, 6.3±2.6% at 4 days and 9.3±4.6% at 6 days. All products were negative for microbial contamination.

Contractile reserve and cardiopulmonary exercise parameters in patients with dilated cardiomyopathy, the two dimensions of exercise testing.

BACKGROUND: Left ventricular (LV) contractile reserve assessed using imaging and cardiopulmonary exercise testing (CPX) has been shown to predict outcome in patients with dilated cardiomyopathy (DCM). Few clinical studies have, however, analyzed the relationship between them. METHODS: A cohort of 75 ambulatory patients with DCM underwent stress treadmill echocardiography with CPX. LV contractile reserve was calculated as absolute change (ΔLVEF=LVEFpeak -LVEFrest ) and percent change (%LVEF=[(LVEFpeak -LVEFrest )/LVEFpeak) ]×100) in LVEF, circumferential and longitudinal strain (LS). Exercise capacity was measured as peak oxygen uptake (peak VO2 ) and ventilatory efficiency as the slope of minute ventilation to CO2 production (VE/VCO2 slope). Values of contractile reserve were compared to matched controls. We also explored which metric of ventricular response (absolute or percent change) was less dependent on baseline LV function. RESULTS: Patients with DCM had a mean age, rest and peak LVEF of 44±10 years, 42±10% and 50±12%, respectively. Among parameters of contractile reserve, peak cardiac output was the strongest parameter associated with peak VO2 (r=.63, P<.001). Along with age, sex, and BMI, it explained more than 70% of the variance in peak VO2 . In contrast, LVEF and LS were only weakly related to peak VO2 . With regard to ventilatory efficiency, the strongest parameter that emerged was right atrial volume index (r=.36, P<.001). Percent change in LVEF was more independent of baseline function than absolute change. CONCLUSION: Echocardiographic contractile reserve and CPX provide complementary information. Percent change in contractile reserve was most independent of baseline function, therefore may be preferred when analyzing the ventricular response to exercise.

Collection and immunoselection of CD34+ cells: the impact of age, sex, and diabetes in patients with chronic heart failure.

BACKGROUND: Mobilized peripheral blood is the most common source of CD34+ cells intended for transplantations. The collection and enrichment of CD34+ cells could be affected by various factors and there are some controversies regarding the effects of patient-related factors. The aim of this study was to assess the impact of age, sex, and diabetes on the CD34+ cell grafts in patients with chronic heart failure. STUDY DESIGN AND METHODS: Cell grafts from 100 adult patients scheduled for autologous CD34+ cell transplantation were investigated. The CD34+ cells were collected using leukapheresis after granulocyte-colony-stimulating factor mobilization and further enriched using the immunomagnetic CD34+ selection. The number of CD34+ cells and their viability were determined by flow cytometry. RESULTS: Older patients had significantly lower CD34+ cell counts than younger patients. The differences between men and women were not found. There was a trend toward an inverse relationship between diabetes and the CD34+ cell count, however, without any significance. No differences in the CD34+ cell viability (97.6% before and 97.9% after selection) were found. The mean CD34+ cell recovery was 59.7% and was not statistically different between age groups, sex, and diabetic patients. CONCLUSION: Before the CD34+ cells are collected the patient's age should be considered. The study did not demonstrate a significant impact of sex and diabetes on the CD34+ cell count. While age and sex did not affect the immunoselection process, diabetes slightly reduced cell recovery. Cell viabilities before and after the cell enrichment were comparable between the tested samples.

Heart rate-guided, but not dose-guided titration of beta blockers stabilizes ventricular repolarization in patients with chronic heart failure.

AIMS: We compared the effects of heart rate-guided and dose-guided beta-blocker titration strategies on QT variability in patients with chronic heart failure (CHF). METHODS: In a prospective study we recorded 5-minute resting high-resolution ECGs (HRECG) in 100 patients with CHF and measured heart rate (HR) and ventricular repolarization by QT variability index (QTVI). In a subgroup of patients not reaching target HR (<70bpm) we uptitrated beta blockers and repeated HRECG measurements 3months thereafter. RESULTS: Target HR was present in 46 patients (group A), and in 54 patients HR was above target (group B). The groups did not differ in age, gender, NYHA class, NT pro-BNP, creatinine, or beta blocker dose. Patients in group A displayed significantly lower QTVI than patients in group B (-1.25±0.55 vs. -1.52±0.42, P=0.013). When uptitrating beta-blockers we found a decrease in HR (from 91±15bpm to 71±15bpm, P<0.001), NTpro BNP levels (from 4474±3878pg/ml to 3042±2566pg/ml, P=0.024), and NYHA class (from 3.0±0.8 to 2.5±0.7, P=0.006). With beta-blocker uptitration QTVI decreased in 10 of 24 patients (42%). In these patients HR decreased more than in the remaining cohort (-25±20bpm vs. -15±17bpm, P=0.017). On multivariate analysis, the presence of target HR was a predictor of QTVI decrease (P=0.017), but beta-blocker dose was not. CONCLUSIONS: In patients with CHF treated by beta-blockers, changes in QT variability appear to occur in parallel with changes of heart rate. This suggests that heart rate-guided titration of beta-blockers may be associated with decreased risk of sudden cardiac death.

LVAD as a Bridge to Heart Transplantation in a Patient with Left Ventricular Noncompaction Cardiomyopathy and Advanced Heart Failure.

Left ventricular noncompaction cardiomyopathy (LVNC) is a rare hereditary cardiomyopathy characterized by the formation of an outer compacted and inner noncompacted layer of the myocardium. The latter is characterized by prominent trabeculations and deep intertrabecular recesses and is functionally inferior to the compacted myocardium. As there is no specific treatment for patients with LVNC who develop heart failure, the management of these patients is limited and many patients progress to advanced stages of the disease. For LVNC patients with advanced heart failure, the data regarding the use of mechanical circulatory support are scarce. We report a case of a 29-year-old patient with LVNC and advanced refractory heart failure, who was successfully bridged to heart transplantation using a long-term continuous-flow left ventricular assist device.

Intracoronary transplantation of CD34(+) cells is associated with improved myocardial perfusion in patients with nonischemic dilated cardiomyopathy.

BACKGROUND: We investigated the effects of intracoronary transplantation of CD34(+) cells on myocardial perfusion in patients with nonischemic dilated cardiomyopathy (DCM). METHODS AND RESULTS: We enrolled 21 patients with DCM (left ventricular ejection fraction [LVEF] <40%, New York Heart Association functional class III) who underwent peripheral stem cell mobilization with granulocyte-colony stimulating factor (G-CSF). CD34(+) cells were collected by means of apheresis. Patients underwent myocardial perfusion imaging, and CD34(+) cells were injected in the coronary artery supplying viable segments with reduced myocardial perfusion and regional dysfunction. Myocardial perfusion imaging was repeated 6 months later. Clinical response to stem cell therapy was predefined as a change in LVEF >5%. The majority of patients were men (81%) with an overall mean age 53 ± 9 years, LVEF 25 ± 5%, and 6-minute walking distance 354 ± 71 m. Myocardial perfusion defects at rest were observed in 86% of patients and were more common in the left anterior descending territory (50%). At 6 months' follow-up, there was a significant improvement in rest myocardial perfusion scores (6.3 ± 5.8 vs 3.1 ± 4.3; P < .001), LVEF (25 ± 7% vs 29 ± 8%; P = .005), and 6-minute walking distance (354 ± 71 m vs 404 ± 91 m; P < .001). Responders to stem cell therapy had lower summed rest perfusion score at both baseline (3.2 ± 3.0 vs 9.1 ± 6.3; P = .015) and follow-up (1.0 ± 1.5 vs 5.0 ± 5.1; P = .028). CONCLUSIONS: CD34(+) cell transplantation may lead to improved myocardial perfusion in patients with nonischemic DCM. Patients with less severe myocardial perfusion defects at baseline may have an increased likelihood to respond to intracoronary CD34(+) cell transplantation.

Immunologic Network and Response to Intramyocardial CD34+ Stem Cell Therapy in Patients With Dilated Cardiomyopathy.

BACKGROUND: Although stem cell therapy (SCT) is emerging as a potential treatment for patients with dilated cardiomyopathy (DCM), clinical response remains variable. Our objective was to determine whether baseline differences in circulating immunologic and nonimmunologic biomarkers may help to identify patients more likely to respond to intramyocardial injection of CD34(+)-based SCT. METHODS AND RESULTS: We enrolled from January 3, 2011 to March 5, 2012 37 patients with longstanding DCM (left ventricular ejection fraction [LVEF] <40%, New York Heart Association functional class III) who underwent peripheral CD34(+) stem cell mobilization with granulocyte colony-stimulating factor (G-CSF) and collection by means of apheresis. CD34(+) cells were labeled with (99m)Tc-hexamethylpropyleneamine oxime to allow assessment of stem cell retention at 18 hours. Response to SCT was predefined as an increase in LVEF of ≥5% at 3 months. The majority (84%) of patients were male with an overall mean LVEF of 27 ± 7% and a median N-terminal pro-B-type natriuretic peptide (NT-proBNP) level of 2,774 pg/mL. Nineteen patients (51%) were responders to SCT. There was no significant difference between responders and nonresponders regarding to age, sex, baseline LVEF, NT-proBNP levels, or 6-minute walking distance. With the use of a partial least squares (PLS) predictive model, we identified 9 baseline factors that were associated with both stem cell response and stem cell retention (mechanistic validation). Among the baseline factors positively associated with both clinical response and stem cell retention were G-CSF, SDF-1, LIF, MCP-1, and MCP-3. Among baseline factors negatively associated with both clinical response and retention were IL-12p70, FASL, ICAM-1, and GGT. A decrease in G-CSF at 3-month follow-up was also observed in responders compared with nonresponders (P = .02). CONCLUSIONS: If further validated, baseline immunologic and nonimmunologic biomarkers may help to identify patients with DCM who are more likely to respond to CD34(+)-based SCT.

Stem cell therapy for chronic heart failure.

PURPOSE OF REVIEW: The aim of this review was to discuss recent advances in clinical aspects of stem cell therapy in heart failure with emphasis on patient selection, stem cell types and delivery methods. RECENT FINDINGS: Several stem cell types have been considered for the treatment of patients with heart failure. In nonischemic heart failure, transplantation of CD34 cells improved myocardial performance, functional capacity and neurohumoral activation. In ischemic heart failure, cardiosphere-derived cells were shown to reduce myocardial scar burden with concomitant increase in viable tissue and regional systolic wall thickening. Both autologous and allogeneic mesenchymal stem cells were shown to be effective in improving heart function in patients with ischemic heart failure; this may represent an important step toward the development of a standardized stem cell product for widespread clinical use. SUMMARY: Although trials of stem cell therapy in heart failure have shown promising results, the findings are not consistent. Given the wide spectrum of heart failure, it may be difficult to define a uniform stem cell therapy for all subsets of patients; instead, future stem cell therapeutic strategies should aim for a more personalized approach by establishing optimal stem cell type, dose and delivery method for an individual patient and disease state.

Effects of intracoronary CD34+ stem cell transplantation in nonischemic dilated cardiomyopathy patients: 5-year follow-up.

RATIONALE: CD34+ transplantation in dilated cardiomyopathy was associated with short-term improvement in left ventricular ejection fraction and exercise tolerance. OBJECTIVE: We investigated long-term effects of intracoronary CD34+ cell transplantation in dilated cardiomyopathy and the relationship between intramyocardial cell homing and clinical response. METHODS AND RESULTS: Of 110 dilated cardiomyopathy patients, 55 were randomized to receive CD34+ stem cell transplantation (SC group) and 55 received no cell therapy (controls). In the SC group, CD34+ cells were mobilized by granulocyte colony-stimulating factor and collected via apheresis. Patients underwent myocardial scintigraphy and cells were injected in the artery supplying segments with the greatest perfusion defect. At baseline, 2 groups did not differ in age, sex, left ventricular ejection fraction, or N-terminal B-type natriuretic peptide levels. At 5 years, stem cell therapy was associated with increased left ventricular ejection fraction (from 24.3 ± 6.5% to 30.0 ± 5.1%; P=0.02), increased 6-minute walk distance (from 344 ± 90 m to 477 ± 130 m; P<0.001), and decreased N-terminal B-type natriuretic peptide (from 2322 ± 1234 pg/mL to 1011 ± 893 pg/mL; P<0.01). Left ventricular ejection fraction improvement was more significant in patients with higher myocardial homing of injected cells. During follow-up, 27 (25%) patients died and 9 (8%) underwent heart transplantation. Of the 27 deaths, 13 were attributed to pump failure and 14 were attributed to sudden cardiac death. Total mortality was lower in the SC group (14%) than in controls (35%; P=0.01). The same was true of pump failure (5% vs. 18%; P=0.03), but not of sudden cardiac death (9% vs. 16%; P=0.39). CONCLUSIONS: Intracoronary stem cell transplantation may be associated with improved ventricular function, exercise tolerance, and long-term survival in patients with dilated cardiomyopathy. Higher intramyocardial homing is associated with better stem cell therapy response.

Increased red cell distribution width is associated with poor stem cell mobilization in patients with advanced chronic heart failure.

Parameters associated with poor CD34(+) stem cell mobilization in advanced chronic heart failure (CHF) patients were investigated. Forty-four CHF patients underwent bone marrow stimulation with granulocyte colony stimulating factor. Poor cell mobilization presents in 32% of patients. Poor and good mobilizers did not differ significantly regarding age, gender, left ventricular ejection fraction, kidney or liver function and exercise capacity. Significant differences were found regarding NT-proBNP levels and red cell distribution width (RDW). Increased RDW was the only independent predictor of poor CD34(+) stem cell mobilization on multivariable analysis and may serve as a biomarker of poor stem cell mobilization in CHF patients.