Phases I–III Clinical Trials Using Adult Stem Cells

First randomized clinical trials have demonstrated that stem cell therapy can improve cardiac recovery after the acute phase of myocardial ischemia and in patients with chronic ischemic heart disease. Nevertheless, some trials have shown that conflicting results and uncertainties remain in the case of mechanisms of action and possible ways to improve clinical impact of stem cells in cardiac repair. In this paper we will examine the evidence available, analyze the main phase I and II randomized clinical trials and their limitations, discuss the key points in the design of future trials, and depict new directions of research in this fascinating field

Impact of short-term mechanical circulatory support with extracorporeal devices on postoperative outcomes after emergency heart transplantation: data from a multi-institutional Spanish cohort

[Abstract] Objectives. We sought to investigate the potential impact of preoperative short-term mechanical circulatory support (MCS) with extracorporeal devices on postoperative outcomes after emergency heart transplantation (HT). Methods. We conducted an observational study of 669 patients who underwent emergency HT in 15 Spanish hospitals between 2000 and 2009. Postoperative outcomes of patients bridged to HT on short-term MCS (n = 101) were compared with those of the rest of the cohort (n = 568). Short-term MCS included veno-arterial extracorporeal membrane oxygenators (VA-ECMOs, n = 23), and both pulsatile-flow (n = 53) and continuous-flow (n = 25) extracorporeal ventricular assist devices (VADs). No patient underwent HT on intracorporeal VADs. Results. Preoperative short-term MCS was independently associated with increased in-hospital postoperative mortality (adjusted odds-ratio 1.75, 95% CI 1.05–2.91) and overall post-transplant mortality (adjusted hazard-ratio 1.60, 95% CI 1.15–2.23). Rates of major surgical bleeding, cardiac reoperation, postoperative infection and primary graft failure were also significantly higher among MCS patients. Causes of death and survival after hospital discharge were similar in MCS and non-MCS candidates. Increased risk of post-transplant mortality affected patients bridged on pulsatile-flow extracorporeal VADs (adjusted hazard-ratio 2.21, 95% CI 1.48–3.30) and continuous-flow extracorporeal VADs (adjusted hazard-ratio 2.24, 95% CI 1.20–4.19), but not those bridged on VA-ECMO (adjusted hazard-ratio 0.51, 95% CI 0.21–1.25). Conclusions. Patients bridged to emergency HT on short-term MCS are exposed to an increased risk of postoperative complications and mortality. In our series, preoperative bridging with VA-ECMO resulted in comparable post-transplant outcomes to those of patients transplanted on conventional support

Preoperative INTERMACS profiles determine postoperative outcomes in critically ill patients undergoing emergency heart transplantation: analysis of the Spanish National Heart Transplant Registry

[Abstract] Background. Postoperative outcomes of patients with advanced heart failure undergoing ventricular assist device implantation are strongly influenced by their preoperative Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profiles. We sought to investigate whether a similar association exists in patients undergoing emergency heart transplantation. Methods and Results. By means of the Spanish National Heart Transplant Registry database, we identified 704 adult patients treated with emergency heart transplantation in 15 Spanish centers between 2000 and 2009. Post-transplant outcomes were analyzed pertaining to patient preoperative INTERMACS profiles, which were retrospectively assigned by 2 blinded cardiologists. Before transplantation, INTERMACS profile 1 (critical cardiogenic shock) was present in 207 patients, INTERMACS profile 2 (progressive decline) in 291, INTERMACS profile 3 (inotropic dependence) in 176, and INTERMACS profile 4 (resting symptoms) was present in 30 patients. In-hospital postoperative mortality rates were, respectively, 43%, 26.8%, and 18% in patients with profiles 1, 2, and 3 to 4 (P<0.001). INTERMACS 1 patients also presented the highest incidence of primary graft failure (1: 31.3%, 2: 22.3%, 3–4: 21.8%; P=0.03) and postoperative need for dialysis (1: 33.2%, 2: 18.9%, 3–4: 21.5%; P<0.001). Adjusted odds-ratios for in-hospital postoperative mortality were 4.38 (95% confidence interval, 2.51–7.66) for profile 1 versus 3 to 4, 2.49 (95% confidence interval, 1.56–3.97) for profile 1 versus 2, and 1.76 (95% confidence interval, 1.02–3.03) for profile 2 versus 3 to 4. Long-term survival after hospital discharge was not influenced by preoperative INTERMACS profiles. Conclusions. Preoperative INTERMACS profiles determine outcomes after emergency heart transplantation. Results call for a change in policies related to the management of heart transplant candidates presenting with INTERMACS profiles 1 and 2

The prognosis of noncutaneous, nonlymphomatous malignancy after heart transplantation: data from the spanish post-heart transplant tumour registry

[Abstract] Introduction. Malignancy is a major complication in the management of solid organ transplant patients. Skin cancers show a better prognosis than other neoplasms, but not all others are equal: Ideally, patient management must take into account the natural history of each type of cancer in relation to the transplanted organs. We sought to determine the prognosis of various groups of noncutaneous nonlymphomatous (NCNL) cancers after heart transplantation (HT). Methods. We retrospectively analyzed the records of the Spanish Post-Heart-Transplant Tumour Registry, which collects data on posttransplant tumors in all patients who have undergone HT in Spain since 1984. Data were included in the study up to December 2008. We considered only the first NCNL post-HT tumors. Results. Of 4359 patients, 375 developed an NCNL cancer. The most frequent were cancers of the lung (n = 97; 25.9%); gastrointestinal tract (n = 52; 13.9%); prostate gland (n = 47; 12.5%; 14.0% of men), bladder (n = 32; 8.5%), liver (n = 14; 3.7%), and pharynx (n = 14; 3.7%), as well as Kaposi's sarcoma (n = 11; 2.9%). The corresponding Kaplan-Meier survival curves differed significantly (P < .0001; log-rank test), with respective survival rates of 47%, 72%, 91%, 73%, 36%, 64%, and 73% at 1 year versus 26%, 62%, 89%, 56%, 21%, 64%, and 73% at 2 years; and 15%, 51%, 77%, 42%, 21%, 64%, and 52% at 5 years post-diagnosis, respectively. Conclusion. Mortality among HT patients with post-HT NCNL solid organ cancers was highest for cancers of the liver or lung (79%–85% at 5 years), and lowest for prostate cancer (23%)

Lung cancer after heart transplantation: results from a large multicenter registry

[Abstract] In this study we analyzed Spanish Post-Heart-Transplant Tumour Registry data for adult heart transplantation (HT) patients since 1984. Median post-HT follow-up of 4357 patients was 6.7 years. Lung cancer (mainly squamous cell or adenocarcinoma) was diagnosed in 102 (14.0% of patients developing cancers) a mean 6.4 years post-HT. Incidence increased with age at HT from 149 per 100 000 person-years among under-45s to 542 among over-64s; was 4.6 times greater among men than women; and was four times greater among pre-HT smokers (2169 patients) than nonsmokers (2188). The incidence rates in age-at-diagnosis groups with more than one case were significantly greater than GLOBOCAN 2002 estimates for the general Spanish population, and comparison with published data on smoking and lung cancer in the general population suggests that this increase was not due to a greater prevalence of smokers or former smokers among HT patients. Curative surgery, performed in 21 of the 28 operable cases, increased Kaplan–Meier 2−year survival to 70% versus 16% among inoperable patients

Estudio de la seguridad a corto y largo plazo del implante intracoronario de células mononucleadas de médula ósea autóloga tras un infarto agudo de miocardio

La reducción de la mortalidad en la fase aguda del infarto merced a los avances terapéuticos han producido un incremento paradójico en la incidencia de insuficiencia cardiaca por remodelado ventricular adverso en los supervivientes. La reducción de la mortalidad en la fase aguda del infarto merced a los avances terapéuticos han producido un incremento paradójico en la incidencia de insuficiencia cardiaca por remodelado ventricular adverso en los supervivientes. La búsqueda de tratamientos para prevenir dicho remodelado y la insuficiencia cardiaca subsecuente es uno de los desafíos más importantes de la investigación traslacional, en el que la terapia celular cobra especial relevancia. El trasplante intracoronario de células mononucleadas de médula ósea autóloga, en pacientes con infarto agudo de miocardio extenso que han recibido terapia de reperfusión y revascularización adecuada del árbol coronario, es factible y seguro a corto y largo plazo. Asimismo, dicha terapia celular podría facilitar la recuperación de la perfusión microvascular, evitar el remodelado e inducir una mejoría de la función ventricular global y regional

Should Advanced Friedreich’s Ataxia Be a Contraindication for Heart Transplantation? A Case Report of a Successful Procedure in a 58-Year-Old Patient

The information on heart transplantation (HT) in patients with Friedreich’s Ataxia (FA) is scarce, and the few published case reports are limited to young patients with mild neurological manifestations. We present the case of a 58-year-old patient with advanced FA (Scale for the Assessment and Rating of Ataxia [SARA] score 30/40), wheelchair-bound for the last 16 years and had urinary incontinence, dysarthria, and neurosensorial deafness. The patient was admitted for a refractory arrhythmic storm and had previous hypertrophic cardiomyopathy that evolved to dilated cardiomyopathy with severely reduced left ventricular ejection fraction and recurrent ventricular arrhythmias. A multidisciplinary team discussed the HT option. The patient was aware of the risks and benefits and considered worthy of the intervention, so he was listed for HT. After a successful surgical intervention, the patient had a long postoperative stay in ICU. He required a high dose of vasopressors, underwent hemofiltration for one month, suffered critical illness myopathy, had several respiratory infections and delayed tracheal extubation. Two and a half months after HT and almost five months at the hospital, the patient was successfully discharged. FA patients with severe heart conditions should be carefully evaluated by a multidisciplinary team to decide the candidacy for HT