Adolfo Villa

Hospital General Universitario Gregorio Marañón, Madrid, Madrid, Spain

Are you Adolfo Villa?

Claim your profile

Publications (20)63.28 Total impact

  • Journal of Cardiology Cases 03/2013; 7(3):e61–e63.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Controversy surrounds the long-term effects of intracoronary bone marrow stem cell transplantation after ST-elevation acute myocardial infarction (STEAMI). We report on the long-term changes in left ventricular function observed in 29 patients with STEAMI who were treated using this technique. Cardiac magnetic resonance imaging was performed at baseline, 6 months after transplantation, and long-term follow-up (median 27 months, interquartile range 24-35 months). The left ventricular ejection fraction had improved significantly by 6 months (from 47.6 ± 8.9% to 52.7 ± 11.6%; P = .001) and this improvement was maintained long-term, at 52.4 ± 11.8% (P = .01 vs. baseline and P = .999 vs. 6 months). There was no significant change from baseline in end-diastolic or end-systolic ventricular volume. Our findings indicate the improvement in injection fraction occurs soon after stem cell transplantation, within the first 6 months, and remains unchanged at long-term follow-up.
    Revista Espa de Cardiologia 03/2011; 64(4):334-7. · 3.20 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The Seventh International Symposium on Stem Cell Therapy and Cardiovascular Innovations was held in Madrid on the 6th and 7th of May 2010. Gathering for the seventh consecutive year the most relevant researchers and opinion leaders on cardiovascular cell therapy, it has become the most important worldwide event on this field. A comprehensive review of the last developments on cell therapy, surgery for heart failure and tissue engineering was made, and the results of three clinical trials were reported. The Symposium was dedicated to the memory of Professor Helmut Drexler.
    Journal of Cardiovascular Translational Research 12/2010; 4(2):115-20. · 3.06 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A growing number of clinical trials are evaluating the effects of stem cell therapy in patients with chronic ischemic heart dysfunction. As most of the clinical trials included a limited and different number of patients, various stem cell sources and several delivery approaches, results vary substantially between these studies. We analyse whether the assessment of myocardial viability may be important when evaluating effects of stem cell transplantation on parameters of left ventricular remodeling. Viability assessment could help to find the best type of stem cell and the best method of cell delivery to be used in chronic ischemic heart dysfunction.
    Cardiovascular & hematological disorders drug targets. 09/2010; 10(3):167-72.
  • [Show abstract] [Hide abstract]
    ABSTRACT: A growing number of clinical trials are evaluating the effects of stem cell therapy in patients with chronic ischemic heart dysfunction. As most of the clinical trials included a limited and different number of patients, various stem cell sources and several delivery approaches, results vary substantially between these studies. We analyse whether the assessment of myocardial viability may be important when evaluating effects of stem cell transplantation on parameters of left ventricular remodeling. Viability assessment could help to find the best type of stem cell and the best method of cell delivery to be used in chronic ischemic heart dysfunction.
    Cardiovascular & Haematological Disorders - Drug Targets(Formerly Current Drug Targets - Cardiovascular & Hematological Disorders) 08/2010; 10(3):167-172.
  • [Show abstract] [Hide abstract]
    ABSTRACT: We tried to evaluate a putative negative effect on coronary atherosclerosis in patients receiving intracoronary infusion of unfractionated bone marrow mononuclear cells (BMMC) following an acute ST-elevation myocardial infarction. Peripheral blood mononuclear cells or enriched CD133(+) BMMC have been associated with accelerated atherosclerosis of the distal segment of the infarct related artery (IRA). Thirty-seven patients with ST-elevation myocardial infarction from the TECAM pilot study underwent intracoronary infusion of autologous BMMC 9 +/- 3.1 days after onset of symptoms. We compared angiographic changes from baseline to 9 months of follow-up in the distal non-stented segment of the IRA, as well as in the contralateral coronary artery, with a matched control group. A subgroup of 15 treated patients underwent additional IVUS within the distal segment of the IRA. No difference between stem cell and control group were found regarding changes in minimum lumen diameter (0.006 +/- 0.42 vs 0.06 +/- 0.41 mm, P = ns) and the percentage of stenosis (-2.68 +/- 12.33% vs -1.78 +/- 8.75%, P = ns) at follow-up. Likewise, no differences were seen regarding changes in the contralateral artery (minimum lumen diameter -0.004 +/- 0.54 mm vs -0.06 +/- 0.35 mm, P = ns). In the intravascular ultrasound substudy, no changes were demonstrated comparing baseline versus follow-up in maximum area stenosis and plaque volume. In this pilot study, analysis of a subgroup of patients found that intracoronary injection of unfractionated BMMC in patients with acute ST-elevation myocardial infarction was not associated with accelerated atherosclerosis progression at mid term. Prospective, randomised studies in large cohorts with long-term angiographic and intravascular ultrasound follow-up are necessary to determine the safety of this therapy.
    American heart journal 06/2010; 159(6):1154.e1-8. · 4.65 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Being one of the main stem cell therapy meetings of the year, the Sixth International Symposium on Stem Cell Therapy and Cardiovascular Innovations was held on April 23rd-24th, 2009, at the Auditorium of the High Council of Scientific Research of Spain (CSIC) in Madrid. Gathering the most prestigious basic researchers and clinical experts in the field of cardiovascular regenerative medicine, the aim of the meeting was to discuss the available evidence and the recent contributions from preclinical investigators, cardiologists, and cardiac surgeons in a participative translational fashion. The role of young "clinician scientists" was reinforced with a special poster session and three awards. The main conclusions of the symposium were (1) that standardization, larger clinical trials, and true translational research are needed, and (2) that new-allogeneic-stem cell products, biotechnological devices, and cell-based bioartificial organs are potentially exciting options for the future.
    Journal of Cardiovascular Translational Research 02/2010; 3(1):1-7. · 3.06 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aims of this study were to assess the safety of drug-eluting stent (DES) use and to compare the incidence of in-stent restenosis (ISR) and neointimal hyperplasia formation according to the type of stent implanted (DES vs bare-metal stents [BMS]) in patients who underwent intracoronary bone marrow mononuclear cell transplantation after acute ST elevation myocardial infarction. Fifty-nine patients with successfully revascularized ST elevation myocardial infarction (37 using BMS and 22 using DES) underwent paired angiographic examinations at baseline and 6 to 9 months after the intracoronary injection of 91 million +/- 56 million autologous bone marrow mononuclear cells. A subgroup of 30 patients also underwent serial intravascular ultrasound examinations. Off-line angiographic assessment showed 4 cases of binary ISR, primarily in BMS (3 cases), and no major adverse cardiac events were associated with stent type (mean follow-up period 41 +/- 10 months). At follow-up, angiographic late luminal loss was significantly lower in patients with DES than in those patients with BMS (0.35 +/- 0.66 vs 0.71 +/- 0.38 mm, p = 0.011). Multivariate analysis identified the use of DES (beta = -0.32, 95% confidence interval [CI] -0.57 to -0.26, p = 0.03) and a smaller baseline reference vessel diameter (beta = 0.29, 95% CI 0.04 to 0.54, p = 0.02) as independent predictors of lower late loss. Moreover, intravascular ultrasound showed a significant reduction of in-stent neointimal hyperplasia formation related to DES use compared with BMS use (Delta neointimal hyperplasia volume 5.4 mm(3) [95% CI 2.7 to 28.1] vs 35.9 mm(3) [95% CI 22.0 to 43.6], p = 0.035). In conclusion, these findings suggest that the use of DES is safe and may prevent ISR and neointimal hyperplasia formation in patients who undergo intracoronary bone marrow mononuclear cell transplantation after a successfully revascularized ST elevation myocardial infarction.
    The American journal of cardiology 07/2009; 103(12):1651-6. · 3.58 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The usefulness the left ventricular ejection fraction as a surrogate endpoint in clinical trials has been confirmed by numerous studies. However, if this approach is to be applied successfully, images must be acquired in a rigorously controlled manner, and it is advisable to use measurement units that have been specifically developed for quantitative analysis of the imaging parameters obtained with current imaging techniques. This review summarizes what is now known about the left ventricular ejection fraction and left ventricular volumes, discusses the importance of measurement units in image analysis, and describes the different imaging techniques available. Finally, there is a discussion of how to select the best imaging technique for specific clinical applications.
    Revista Espa de Cardiologia 06/2009; 62(5):535-51. · 3.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The Fifth International Symposium on Stem Cell Therapy and Applied Cardiovascular Biotechnology was held on April 24th-25th, 2008, at the Auditorium of the High Council of Scientific Research of Spain (CSIC) in Madrid, as a continuation of a series of yearly meetings, organized in an attempt to encourage translational research in this field and facilitate a positive interaction among experts from several countries, along with industry representatives and journalists. In addition, members of the Task Force of the European Society concerning the clinical investigation of the use of autologous adult stem cells for repair of the heart gathered and discussed an update of the previous consensus, still pending of publication. In this article, we summarize some of the main topics of discussion, the state-of-the-art and latest advances in this field, and new challenges brought up for the near future.
    Journal of Cardiovascular Translational Research 03/2009; 2(1):108-13. · 3.06 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Over the past decade, cell therapy has emerged as a new approach to reversing myocardial ischemia. Several types of adult stem cells have been studied in both preclinical and clinical conditions for this purpose: bone marrow cells, circulating cells, and myoblasts. Nevertheless, the quest for the ideal "anti-ischemic" cell is still ongoing. Recently, the existence of a population of stem cells located in adipose tissue (adipose-derived stem cells) has been observed. These are able to differentiate into multiple cell lineages including cardiomyocytic differentiation. In this review we discuss the basic principles of adipose-derived stem cells (types and characteristics, harvesting, and expansion), the initial experimental studies, and the currently ongoing clinical trials.
    Cell Transplantation 02/2009; 18(3):245-54. · 4.42 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The usefulness the left ventricular ejection fraction as a surrogate endpoint in clinical trials has been confirmed by numerous studies. However, if this approach is to be applied successfully, images must be acquired in a rigorously controlled manner, and it is advisable to use measurement units that have been specifically developed for quantitative analysis of the imaging parameters obtained with current imaging techniques. This review summarizes what is now known about the left ventricular ejection fraction and left ventricular volumes, discusses the importance of measurement units in image analysis, and describes the different imaging techniques available. Finally, there is a discussion of how to select the best imaging technique for specific clinical applications.
    Revista Espanola De Cardiologia - REV ESPAN CARDIOL. 01/2009; 62(5):535-551.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Late contrast-enhanced cardiac magnetic resonance (CMR) enables areas of persistent microvascular obstruction (PMO) to be detected early after acute myocardial infarction. Our aim was to evaluate the impact of PMO on subsequent ventricular remodeling in a cohort of patients with acute ST-elevation myocardial infarction (STEMI) who underwent intracoronary autologous bone-marrow mononuclear cell (ABMMC) transplantation. In total, 14 patients underwent intracoronary transplantation of 66+/-39 x 10(6) ABMMCs 8+/-2 days following successful revascularization of a STEMI (i.e., TIMI flow grade 3 in the affected artery). Serial CMR studies with gadolinium-DTPA enhancement were performed at baseline and 10 months after infarction. Left ventricular volume and ejection fraction, regional contractility and the infarct size were measured and the presence of PMO (defined as hypoenhanced areas within the infarcted zone) was investigated. Overall, PMO was detected in five of the 14 patients (36%). Those with PMO tended to have a larger infarct size, larger ventricular volumes, and poorer regional and global left ventricular systolic function in baseline studies than those without PMO. At follow-up, there were significant associations between PMO and an increase in end-diastolic volume (25+/-24 mL vs. -2+/-19 mL; P=.037), the absence of an increase in end-diastolic parietal thickness (P=.027), and a smaller reduction in the number of akinetic or dyskinetic segments. The detection of PMO by CMR early after successful revascularization of a STEMI in patients who underwent intracoronary ABMMC transplantation was associated with adverse left ventricular remodeling.
    Revista Espa de Cardiologia 07/2008; 61(6):602-10. · 3.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction and objectivesLate contrast-enhanced cardiac magnetic resonance (CMR) enables areas of persistent microvascular obstruction (PMO) to be detected early after acute myocardial infarction. Our aim was to evaluate the impact of PMO on subsequent ventricular remodeling in a cohort of patients with acute ST-elevation myocardial infarction (STEMI) who underwent intracoronary autologous bone-marrow mononuclear cell (ABMMC) transplantation.MethodsIn total, 14 patients underwent intracoronary transplantation of 66 (39) × 106 ABMMCs 8 (2) days following successful revascularization of a STEMI (ie, TIMI flow grade 3 in the affected artery). Serial CMR studies with gadolinium-DTPA enhancement were performed at baseline and 10 months after infarction. Left ventricular volume and ejection fraction, regional contractility, and the infarct size were measured and the presence of PMO (defined as hypoenhanced areas within the infarcted zone) was investigated.ResultsOverall, PMO was detected in five of the 14 patients (36%). Those with PMO tended to have a larger infarct size, larger ventricular volumes, and poorer regional and global left ventricular systolic function in baseline studies than those without PMO. At follow-up, there were significant associations between PMO and an increase in end-diastolic volume (25 [24] mL vs −2 [19] mL; P=.037), the absence of an increase in end-diastolic parietal thickness (P=.027), and a smaller reduction in the number of akinetic or dyskinetic segments.ConclusionsThe detection of PMO by CMR early after successful revascularization of a STEMI in patients who underwent intracoronary ABMMC transplantation was associated with adverse left ventricular remodeling.Introducción y objetivosLa cardiorresonancia magnética con realce tardío de contraste (RMc) permite la detección precoz de obstrucción microvascular persistente (OMP) tras un infarto. Hemos analizado el impacto de la OMP en el remodelado ventricular de una cohorte de pacientes con infarto agudo de miocardio con ST elevado (IAMSTE) que recibieron implante intracoronario de células mononucleadas de médula ósea autóloga (CMMOA).MétodosCatorce pacientes recibieron infusión intracoronaria de 66 ± 39 millones de CMMOA a los 8 ± 2 días de un IAMSTE revascularizado con éxito (flujo TIMI 3 epicárdico). Se realizaron estudios seriados de RMc con gadolinio-DTPA (basal y a los 10 meses del infarto), con análisis de volúmenes y fracción de eyección ventricular izquierda, motilidad regional, tamaño del infarto y presencia de OMP (definida como un área con ausencia de señal en el seno del infarto).ResultadosSe detectó OMP en 5 (36%) de los 14 pacientes, junto con una tendencia en el estudio basal a presentar un mayor tamaño del infarto, mayores volúmenes y peor función sistólica general y regional de ventrículo izquierdo respecto a aquellos sin OMP. En el seguimiento la presencia de OMP se relacionó significativamente con un incremento en el volumen telediastólico (25 ± 24 frente a −2 ± 19 ml; p = 0,037), ausencia de incremento en el grosor telediastólico parietal (p = 0,027) y una menor reducción en el número de segmentos acinéticos o discinéticos.ConclusionesLa OMP evaluada precozmente mediante RMc tras un IAMSTE revascularizado con éxito se asocia con un remodelado ventricular izquierdo adverso en pacientes sometidos a implante intracoronario de CMMOA.
    Revista Espanola de Cardiologia 01/2008; · 3.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We describe the appearance of delayed episodes of ventricular arrhythmias in 4 patients out of 72 undergoing intracoronary transplantation of autologous bone marrow mononuclear cells (BMMC) following ST elevated myocardial infarction (STEMI). Two cases with severely depressed systolic function presented electrical storms with monomorphic sustained ventricular tachycardia (SVT) within 2 to 3 days following cell transplantation, even though there were no periprocedural complications. Both patients were implanted with an internal defibrillator (ICD) after ruling out coronary re-occlusion. The remaining 2 patients presented several asymptomatic episodes of non-sustained ventricular tachycardia within one month following cell transfer. Only one of the latter presented syncopal SVT through programmed ventricular stimulation, undergoing ICD implantation afterwards. Neither new arrhythmic episodes nor ICD interventions have occurred during later follow-up of the three ICD patients (639+/-59 days). Information from large multicenter databases and our historical cohort of STEMI patients indicates that the rate of VT occurring within the first weeks after the initial 48 hours of infarction is significantly lower than that observed in our cell-therapy experience. The lack of information regarding the appearance of malignant arrhythmias in patients with severe systolic dysfunction following this type of therapy after STEMI requires us to be extremely cautious. However, any claim of a mechanism related to cell transfer would be completely speculative with the available data. Therefore, our only aim when reporting our findings is to recommend a short but longer stay (2-3 days) following cell transplantation, particularly in patients with a natural tendency to develop arrhythmic events.
    Europace 01/2008; 9(12):1222-3. · 2.77 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction and objectives Late contrast-enhanced cardiac magnetic resonance (CMR) enables areas of persistent microvascular obstruction (PMO) to be detected early after acute myocardial infarction. Our aim was to evaluate the impact of PMO on subsequent ventricular remodeling in a cohort of patients with acute ST-elevation myocardial infarction (STEMI) who underwent intracoronary autologous bone-marrow mononuclear cell (ABMMC) transplantation. Methods In total, 14 patients underwent intracoronary transplantation of 66±39 × 106 ABMMCs 8±2 daysfollowing successful revascularization of a STEMI (i.e., TIMI flow grade 3 in the affected artery). Serial CMR studies with gadolinium-DTPA enhancement were performed at baseline and 10 months after infarction. Left ventricular volume and ejection fraction, regional contractility and the infarct size were measured and the presence of PMO (defined as hypoenhanced areas within the infarcted zone) was investigated. Results Overall, PMO was detected in five of the 14 patients (36%). Those with PMO tended to have a larger infarct size, larger ventricular volumes, and poorer regionaland global left ventricular systolic function in baseline studies than those without PMO. At follow-up, there were significant associations between PMO and an increase in end-diastolic volume (25±24 mL vs. −2±19 mL; P=.037), the absence of an increase in end-diastolic parietal thickness (P=.027), and a smaller reduction in the number of akinetic or dyskinetic segments. Conclusions The detection of PMO by CMR early after successful revascularization of a STEMI in patients who underwent intracoronary ABMMC transplantation was associated with adverse left ventricular remodeling.
    Revista Espanola De Cardiologia - REV ESPAN CARDIOL. 01/2008; 61(6):602-610.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cardiac stem cell therapy with bone-marrow-derived stem cells is a promising approach to facilitate myocardial regeneration after acute myocardial infarction or in congestive heart failure. The clinical data currently available seem to indicate that this approach is safe and is not associated with an increase in the number of adverse clinical events; nevertheless, the level of safety confidence is limited because of the small number of patients who have been treated and the absence of long-term clinical follow-up data. In order to establish the clinical safety of cardiac stem cell therapy, it will be necessary to collect additional data from both previous and ongoing clinical trials in subsets of patients relative to their background risk. Several conceptual safety concerns should also be addressed. These concerns relate to a number of operational mechanisms and include biological effects on differentiation, remote homing of transplanted stem cells, progression of atherosclerosis, and arrhythmias. The proactive scrutiny of these phenomena could eventually facilitate the translation of the promise of cardiac regeneration into a safe and effective therapy.
    Nature Clinical Practice Cardiovascular Medicine 03/2007; 4 Suppl 1:S100-5. · 7.04 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Since the feasibility of stem cell therapy has been recognized, enthusiasm for this therapy has grown exponentially. Nevertheless, as professionals we must realize that this enthusiasm should relate not only to our scientific interest but also to the care of our patients. Within the next decade, patients' demand for the latest therapies is likely to rise because of changes in health care systems that will broaden availability. Stem cell therapy is likely to be among these in-demand treatments, and we must be prepared for this change. In this Review we discuss the basic principles of how to launch a clinical program for stem cell therapy for cardiovascular repair. First, we look at the composition of the program team. Second, we describe the different types of stem cells available in clinical practice. Third, we present in depth the two most widely applicable delivery approaches. Finally, we discuss selection of patients and approaches and clinical and imaging methods by which to evaluate the safety and efficacy of this therapy.
    Nature Clinical Practice Cardiovascular Medicine 03/2007; 4 Suppl 1:S123-9. · 7.04 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In this review we summarize the available evidence regarding the application of stem cell therapy for human cardiovascular repair, going over the principal concepts that will help us understand the present and future of this therapy: first the different types of cells available in clinical practice, second the delivery approaches, and third highlighting the most important clinical studies and their efficacy and safety results. In addition, we also speculate on the value of current clinical data to gain an insight into the mechanism of stem cell-based cardiac repair and to design clinical trials in the future.
    Annals of Medicine 02/2007; 39(6):412-27. · 4.73 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Not long ago, it was assumed that mammalian hearts were so differentiated that regeneration of cardiac tissue was not possible, but now an increasing amount of information suggests that the intrinsic regenerative capacity of the heart can be encouraged by stimulating resident stem cells or transplanting extracardiac progenitor cells. In the future, cardiovascular stem cell therapy may be administered to all patients. Here, we review what has happened and look at where we are going.
    Nature Clinical Practice Cardiovascular Medicine 04/2006; 3 Suppl 1:S138-51. · 7.04 Impact Factor