Comment on the 'pilot' GRACIA-2 randomized trial: reply

We thank Dr Villata et al. for their thought-provoking comments.Their concern about the suitableness to choose combined endpointsin clinical trials deserves some comment.     

Panoramic View of The Fifth International Symposium on Stem Cell Therapy and Applied Cardiovascular Biotechnology, April 2008, Madrid (Spain)

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.     

Hospital without dyspnea: rationale and design of a multidisciplinary intervention

Dyspnea is a common and disabling symptom of respiratory and heart diseases, which is growing in incidence. During hospital admission, breathlessness is under-diagnosed and under-treated, although there are treatments available for controlling the symptom. We have developed a tailored implementation strategy directed to medical staff to promote the application of these pharmacological and non-pharmacological tools in dealing with dyspnea. The primary aim is to decrease the rate of patients that do not receive an adequate relief of dyspnea. This is a four-stage quasi-experimental study. The intervention consists in two teaching talks that will be taught in Cardiology and Respiratory Medicine Departments. The contents will be prepared by Palliative Care specialists, based on available tools for management of dyspnea and patients’ needs. A cross-sectional study of dyspnea in hospitalized patients will be performed before and after the intervention to ascertain an improvement in dyspnea intensity due to changes in medical practices. The last phase consists in the creation of consensus protocols for dyspnea management based in our experience. The results of this study are expected to be of great value and may change clinical practice in the near future and promote a changing for the better of dyspnea care.     

Coronary stent implantation in patients older than 75 years of age: clinical profile and initial and long-term (3 years) outcome

Objective The objective of this study was to compare the initial and long-term outcome of elderly and younger patients after coronary stent implantation. Methods The evolutions of 76 patients aged >75 years and of 860 patients aged ≤75 years who underwent consecutive stenting (from June 1991 to June 1997) were compared in a cohort study. Results The elderly patients had lower left ventricular ejection fractions (0.58 ± 0.14 vs 0.61 ± 0.13; P = .03) and more frequently had unstable angina (78.9% vs 55.3%; P <.0001), previous heart failure (10.5% vs 4.9%; P = .03), and multivessel disease (68.4% vs 58.3%; P = .08). After the procedure, the elderly patients showed a higher inhospital mortality rate (6.6% vs 2.4%; P = .03) and myocardial infarction rate (5.3% vs 1.7%; P = .04). The long-term follow-up period (mean, 3.2 ± 1.4 years; median, 3.0 years) showed in the elderly a higher mortality rate (15.4% vs 5.8%; P = .006), a lower rate of repeat revascularization (9.2% vs 19.7%; P = .04), and a similar incidence rate of major adverse cardiac events (27.7% vs 28.2%; P = .93). Multivariate analysis of the elderly group identified female gender (hazard ratio, 2.19; 95% CI, 1.18 to 4.06; P = .012) and presence of multivessel disease (hazard ratio, 2.35; 95% CI, 1.05 to 5.26; P = .037) as independent predictors of further events. Conclusion Patients aged >75 years have a less favorable baseline profile and higher inhospital and 3-year mortality rates. However, the incidence rate of major adverse cardiac events in the long term is acceptable and similar to that of younger patients. (Am Heart J 2002;143:620-6.)     

Bone-marrow-derived cells for cardiac stem cell therapy: safe or still under scrutiny?

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.     

End-of-life care in a cardiology department: have we improved?

Background End-of-life care is not usually a priority in cardiology departments. We sought to evaluate the changes in end-of-life care after the introduction of a do-not-resuscitate (DNR) order protocol. Methods & Results Retrospective analysis of all deaths in a cardiology department in two periods, before and after the introduction of the protocol. Comparison of demographic characteristics, use of DNR orders, and end-of-life care issues between both periods, according to the presence in the second period of the new DNR sheet (Group A), a conventional DNR order (Group B) or the absence of any DNR order (Group C). The number of deaths was similar in both periods (n = 198 vs. n = 197). The rate of patients dying with a DNR order increased significantly (57.1% vs. 68.5%; P = 0.02). Only 4% of patients in both periods were aware of the decision taken about cardiopulmonary resuscitation. Patients in Group A received the DNR order one day earlier, and 24.5% received it within the first 24 h of admission (vs. 2.6% in the first period; P < 0.001). All patients in Group A with an implantable cardioverter defibrillator (ICD) had shock therapies deactivated (vs. 25.0% in the first period; P = 0.02). Conclusions The introduction of a DNR order protocol may improve end-of-life care in cardiac patients by increasing the use and shortening the time of registration of DNR orders. It may also contribute to increase ICD deactivation in patients with these orders in place. However, the introduction of the sheet in late stages of the disease failed to improve patient participation.