Francisco Fernández Avilés

RegeneraciÓn miocárdica mediante la implantaciÓn intracoronaria de células madre en el infarto agudo de miocardio

Introduccion y objetivos Trabajos experimentales y clinicos sugieren que el tejido necrotico tiene la capacidad de regenerarse. Nuestro grupo ha comenzado un estudio clinico para demostrar que la implantacion intracoronaria de celulas madre es un procedimiento factible y seguro. Presentamos los resultados de nuestros primeros 5 pacientes. Pacientes y metodo Se ha incluido a pacientes con un infarto agudo de miocardio anterior y una lesion unica en la descendente anterior reparada mediante angioplastia primaria o facilitada. A los 10-15 dias del infarto, se procedio a la extraccion de medula osea. El implante celular se hizo por via intracoronaria. El protocolo de seguimiento incluye ecocardiografia con dobutamina, resonancia magnetica y Holter de ECG basal y a los 6 meses. Resultados Ningun paciente ha tenido un evento cardiaco tras 6 meses de seguimiento. En un paciente se observo un accidente isquemico transitorio sin secuelas. No se han demostrado arritmias en ninguno de los pacientes. El volumen telediastolico no vario a los 6 meses (159 ± 25 y 157 ± 16 ml), el volumen telesistolico disminuyo (77 ± 22 y 65 ± 16 ml) y la fraccion de eyeccion aumento (53 ± 7 y 58 ± 8%), aunque no hubo diferencias significativas. En los 3 pacientes en los que la ecocardiografia con dobutamina descarto viabilidad, si hubo una disminucion significativa de los volumenes. Conclusiones El implante intracoronario de celulas madre en pacientes que han tenido un infarto agudo de miocardio parece un metodo seguro y factible, y podria dar lugar a un remodelado favorable.

Intracoronary stem cell transplantation in acute myocardial infarction

INTRODUCTION AND OBJECTIVES Experimental and clinical studies suggest that necrotic myocardium may have the capacity to regenerate. We have started a clinical study to demonstrate that the intracoronary implantation of stem cells is feasible and safe. The results in our first 5 patients are presented here. PATIENTS AND METHOD We included patients with anterior acute myocardial infarction and isolated stenosis of the left anterior descending artery that was successfully repaired by primary or facilitated angioplasty. Patients received an intracoronary infusion of bone marrow-derived cells 10-15 days after the infarction. The follow-up protocol included low-dose dobutamine echocardiography, magnetic resonance studies and ECG Holter monitoring. RESULTS The procedure was carried out with no complications. No patient had a cardiac event during the first 6 months. One patient had a transient ischemic attack without sequelae. No arrhythmias were found. Left ventricular end-diastolic volume remained the same at 6 months (159+/-25 ml, 157+/-16 ml), left ventricular end-systolic volume decreased (77+/-22 ml, 65+/-16 ml), and the ejection fraction increased (53+/-7%, 58+/-8%) although no statistically significant differences were found. In the 3 patients in whom dobutamine echocardiography ruled out viability, we found a significant reduction in both volumes. CONCLUSIONS Intracoronary bone marrow-derived cell transplantation after an acute myocardial infarction seems to be safe and feasible, and might lead to favorable remodeling.

Improved Prognosis After Using Mild Hypothermia to Treat Cardiorespiratory Arrest Due to a Cardiac Cause: Comparison With a Control Group

INTRODUCTION AND OBJECTIVES Patients who survive a cardiac arrest have a poor short-term prognosis in terms of mortality and neurological function. The use of mild hypothermia has been investigated in only a few randomized studies, but appears to be effective for treating these patients. The aim of this study was to investigate the effect of this treatment on survival and neurological outcomes. METHODS We compared mild hypothermia and usual treatment in patients who had experienced a prolonged cardiac arrest due to ventricular fibrillation or tachycardia and who showed signs of neurological damage. Patient were divided into two groups: a control group of 28 patients and a group of 41 patients who were treated with hypothermia. Patients were assessed at discharge and at 6 months. RESULTS There was no significant difference between the two groups in baseline characteristics, including those of the cardiac arrest, or in the time to treatment. At discharge, neurological status was good in 18 patients (43.9%) in the hypothermia group but in only five (17.9%) in the control group (risk ratio=2.46; 95% confidence interval, 1.11-3.98; P=.029). At 6 months after discharge, neurological status was found to be good in 19 patients (46.3%) in the treatment group and six (21.4%) in the control group (risk ratio=2.16; 95% confidence interval, 1.05-3.36; P=.038). The effect of hypothermia may have been affected by various confounding factors. CONCLUSIONS Our findings demonstrate that hypothermic treatment after cardiac arrest prolonged by ventricular fibrillation or tachycardia helps improve the prognosis of anoxic encephalopathy.

Órdenes de no reanimar y cuidados paliativos en pacientes fallecidos en un servicio de cardiología. ¿Qué podemos mejorar?

Con el objetivo de evaluar el uso de ordenes de no reanimar y de cuidados paliativos en cardiopatas, registramos 198 muertes consecutivas en nuestro servicio. En 113 (57%) se decidio no reanimar, se reflejo en la historia clinica en 102 (90,3%) y en 74 (65,5%) en las hojas de enfermeria. Se informo a 5 pacientes (4,4%) y a 95 familias (84,1%). El uso de medidas paliativas fue escaso en pacientes no reanimables, 56 (49,6%) recibieron cloruro morfico y 5 (4,4%), asistencia espiritual. Sin embargo, previamente a la orden de no reanimar recibieron con frecuencia tratamientos agresivos y costosos como intubacion orotraqueal, 49 (43,4%), coronariografia, 27 (23,9%), inotropicos, 55 (48,7%) y balon intraaortico de contrapulsacion, 15 (13,3%). Concluimos que casi tres quintos de los pacientes que mueren en un servicio de cardiologia no se consideran subsidiarios de reanimacion, tomandose con frecuencia esa decision tras realizar procedimientos agresivos, con una posterior infrautilizacion de medidas paliativas.

Imbalance Between the Supply and Demand for Cardiologists in Spain. Analysis of the Current Situation, Future Prospects, and Possible Solutions

Planning cardiology provision in Spain requires knowledge of the resources available and the demand, both now and in the future. In this report, we present the results of a study carried out by the Spanish Society of Cardiology on the availability of and demand for cardiologists in the country. The current situation is characterized by an imbalance of around 14% between the number of active cardiologists and the estimated number required. The demographic distribution of cardiologists shows that they are predominantly male and middle-aged. Expectations are that the situation will get worse until the year 2020. To correct this imbalance, alternative forms of training or clinical department organization, or both, are required. Some possible alternatives are presented in the final part of this document, as proposals for open discussion.

Additional value of screening for minor genes and copy number variants in hypertrophic cardiomyopathy

Introduction Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited heart disease. Next-generation sequencing (NGS) is the preferred genetic test, but the diagnostic value of screening for minor and candidate genes, and the role of copy number variants (CNVs) deserves further evaluation. Methods Three hundred and eighty-seven consecutive unrelated patients with HCM were screened for genetic variants in the 5 most frequent genes (MYBPC3, MYH7, TNNT2, TNNI3 and TPM1) using Sanger sequencing (N = 84) or NGS (N = 303). In the NGS cohort we analyzed 20 additional minor or candidate genes, and applied a proprietary bioinformatics algorithm for detecting CNVs. Additionally, the rate and classification of TTN variants in HCM were compared with 427 patients without structural heart disease. Results The percentage of patients with pathogenic/likely pathogenic (P/LP) variants in the main genes was 33.3%, without significant differences between the Sanger sequencing and NGS cohorts. The screening for 20 additional genes revealed LP variants in ACTC1, MYL2, MYL3, TNNC1, GLA and PRKAG2 in 12 patients. This approach resulted in more inconclusive tests (36.0% vs. 9.6%, p<0.001), mostly due to variants of unknown significance (VUS) in TTN. The detection rate of rare variants in TTN was not significantly different to that found in the group of patients without structural heart disease. In the NGS cohort, 4 patients (1.3%) had pathogenic CNVs: 2 deletions in MYBPC3 and 2 deletions involving the complete coding region of PLN. Conclusions A small percentage of HCM cases without point mutations in the 5 main genes are explained by P/LP variants in minor or candidate genes and CNVs. Screening for variants in TTN in HCM patients drastically increases the number of inconclusive tests, and shows a rate of VUS that is similar to patients without structural heart disease, suggesting that this gene should not be analyzed for clinical purposes in HCM.

Impact of Beta Blockers on Dobutamine-Atropine Stress Echocardiography.

Dobutamine increases oxygen demand in the myocardium and is used in conjunction with echocardiography to detect coronary artery disease. Beta blockers (BB) are partial antagonists of dobutamine and, therefore, offset dobutamine effects. Still, the impact of BB therapy on dobutamine stress echocardiography is not clear. One hundred forty‐one dobutamine‐atropine echocardiographic studies have retrospectively been analyzed: 27 patients were on BB (19%; group I); and 114 off BB (81%; group II). Coronary angiography was performed in a similar percentage of patients (97% and 85%, respectively; P = NS). No differences in clinical and angiographic profile were found between the groups. Sensitivity (83% vs 71%; P = NS) and specificity (100% vs 95%; P = NS) for coronary artery disease were similar in both groups. Atropine was infused more frequently to patients from group I (67% vs 46%; P = 0.04). Limiting side effects and prolonged ischemia presented with the same frequency in both groups. When the dobutamine test was positive, severe extent of ischemia appeared more often in patients from group I than in patients from group II (66% vs 33%; P = 0.03). The majority of patients from group I (55%) with severe extent of ischemia and only 12% from group II received atropine (P = 0.02). No differences were found in dobutamine time and extent of ischemia in patients from group I who had a positive response to dobutamine. On the contrary, patients from group II with one vessel disease had a dobutamine time longer (10.5 ± 3.8 vs 7.8 ± 3.7 min; P < 0.05) and extent of ischemia smaller (1.8 ± 0.4 vs 2.6 ± 0.5 segments; P < 0.05) than patients from group II with multivessel disease. We conclude that: 1) sensitivity of dobutamine‐atropine echocardiography for diagnosis of coronary artery disease remains even if patients are on BB; 2) patients with significant coronary artery disease who are taking BB often develop severe myocardial ischemia during dobutamine‐atropine stress echocardiography; and 3) BB therapy precludes stratification of a positive echocardiographic response. These conclusions should be confirmed in a prospective study to be considered as definitive.

Chest Pain With an Elevated Troponin Level but Without Significant Coronary Artery Disease Is Not Usually Due to an Infarction

1. Azar F, Pérez de Isla L, Moreno M, Landaeta A, Refoyo E, López Fernández T, et al. Evaluación de tamaño, función y rangos de normalidad de la asincronía de la aurícula izquierda en sujetos sanos mediante ecocardiografía tridimensional. Rev Esp Cardiol. 2009;62:816-9. 2. Aune E, Baekkevar M, Roislien J, Rodevand O, Otterstad JE. Normal reference ranges for left and right atrial volume indexes and ejection fractions obtained with real-time three-dimensional echocardiography. Eur J Echocardiogr. 2009;10:738-44. 3. Badano LP, Pezzutto N, Marinigh R, Cinello M, Nucifora G, Pavoni D, et al. How many patients would be misclassified using M-mode and two-dimensional estimates of left atrial size instead of left atrial volume? A three-dimensional echocardiographic study. J Cardiovasc Med (Hagerstown). 2008;9:476-84.

The Scope of Cardiological Competence in New Clinical Settings. Spanish Society of Cardiology Consensus Document

Cardiology is the medical discipline or specialty responsible for the prevention, diagnosis, and treatment of cardiovascular disease. As this is the major cause of morbidity and mortality in Spain and the European Union,1 cardiology professionals have, with respect to other medical specialists, an additional moral authority and responsibility derived from the relevance for society of an excellent performance in combating cardiovascular disease. Hence the importance of keeping up with the rapid transitions that are currently taking place at the social, administrative, educational, health care, and professional levels, transitions that necessarily generate novel contexts for the practice of cardiology and for its professionals. At the end of 2005, the Spanish Society of Cardiology (SSC), by virtue of its leadership role in combating cardiovascular disease, decided to undertake a project, applying a synthetic approach to the process matrix, involving the professionals in cardiology and in other medical specialties, the health care administrations, the pharmaceutical industry, and biotechnology companies, the institutions, the patients and the general population; these processes will ultimately play a role in the development of the field of cardiology, in the work of The Scope of Cardiological Competence in New Clinical Settings

Impact of left ventricular late enhancement on pulmonary arterial hypertension in idiopathic dilated cardiomyopathy

Methods 71 consecutive patients (p) with DCM, left ventricular systolic dysfunction (LVEF<35%) and normal coronary angiography followed in an outpatient HF clinic, were prospectively enrolled in two institutions. All p had to be in stable clinical condition in the last month. Exclusion criteria were: contraindications for contrast-enhanced cardiac MR (ce-CMR), significant impairment of lung function by clinical criteria or spirometry and history of thromboembolic disease. All patients underwent ECG, echo, blood test and a ce-CMR study in a Philips Intera ® 1.5 T scanner, which included cine imaging, phase contrast in the main pulmonary artery and aorta and late enhancement (LE). Postprocessing was performed with QMASS 7.2 ® (Medis, The Netherlands). PVR was calculated following the equation: 19.38 -(4.62*Ln pulmonary artery average velocity) (0.08 x RVEF %)