Iago Sousa

Impact of time to cooling initiation and time to target temperature in patients treated with hypothermia after cardiac arrest

Purpose: Little is known about the role of time to initiation of therapeutic hypothermia and time to target temperature (TTT) in the prognosis of patients resuscitated from cardiac arrest. Methods: A retrospective analysis was performed in 145 survivors of cardiac arrest who underwent therapeutic hypothermia between January 2003 and January 2013. The objective was to identify predictors of survival free from significant neurological sequelae (Cerebral Performance Categories Scale (CPC): >2) six months after cardiac arrest. We evaluated the effect of faster and earlier cooling. Results: Overall survival at six months was 42.1% (61 patients); 59 of these were considered to have a good neurological status (CPC≤2), and in whom therapeutic hypothermia was initiated earlier (87±17 min vs. 111±14 min; p=0.042), and the target temperature was reached at an earlier time (TTT: 316 ± 30 min vs. 365 ± 27 min; p=0.017). Multivariate analysis selected longer duration of cardiac arrest (odds ratio (OR) =1.06 per min), a non-shockable initial rhythm (OR=13.8), severe acidosis (OR=0.009 per 0.01 unit), older age (OR=1.04 per year) and longer TTT (OR=1.005 per min) as associated with poor prognosis. Conclusion: The most important prognostic factors for death or lack of neurological recovery in patients with cardiac arrest treated with therapeutic hypothermia are initial-rhythm, time from cardiac arrest to return of spontaneous circulation and arterial-pH at admission. Although the speed of cooling initiation and the time to reach target temperature may play a role, its influence on prognosis seems to be less important.

Early intravenous immunoglobulin replacement in hypogammaglobulinemic heart transplant recipients: results of a clinical trial.

Immunoglobulin G (IgG) hypogammaglobulinemia (HGG) is a risk factor for development of severe infections after heart transplantation. We performed a clinical trial to preliminarily evaluate the efficacy and safety of early administration of intravenous immunoglobulin (IVIG) for prevention of severe infection in heart recipients with post‐transplant IgG HGG.

Tako-tsubo cardiomyopathy triggered by multiple shocks in electrical storm

Tako-tsubo cardiomyopathy (TTC) is a syndrome characterized by acute transient ventricular dysfunction in the absence of obstructive coronary artery disease and is predominantly associated with exposure to sudden emotional or physical stress. Patients with TTC may develop serious in-hospital complications, including ventricular arrhythmias. However, triggering of TTC after an electrical storm has not previously been described. We present two cases of TTC induced by multiple shocks in the setting of an electrical storm due to pharmacologically induced long QT syndrome.

Immune Monitoring of Regulatory CD4 T Cells in Heart Recipients Using One-Single Dose Versus Two-Dose Basiliximab Induction

Background The use of induction immunosuppressive therapies in heart transplantation (HT) is still controversial. Delay in the initiation and reduced calcineurin inhibitor dose, due to renal failure and other settings are used as potential indications to induction use in some centers. On the other hand minimization of doses of monoclonal antibodies for induction therapy is indicated in some clinical settings such as high infection risk. Immunemonitoring of lymphocyte subsets after induction therapy might provide useful information. Methods In a retrospective single center analysis of data prospectively collected, a comparative analysis of the kinetics of lymphocyte subsets was performed in patients using the recommended two doses [2D] of anti-IL2R-alpha monoclonal antibodies (Basiliximab, 20 mg, n=18) versus a single dose (1D, n=32). This was a non interventional study, single dose was indicated in specific clinical settings. We analysed the kinetics of regulatory CD4 T cells during the first 6 months after transplantation. Assessment points were pre-HT, day [d] 7, d15, d30, d60, d90 and d180. Maintenance immunosuppression included steroids, tacrolimus and mycophenolate mofetil in a similar way in both groups. Percentages and total counts of lymphocyte subsets were studied by flow-cytometry. Results Baseline (pre-HT) percentages were similar in both groups (5.45±2.48 vs 5.36±3.31%, p=0.93). In 2D group, a decrease of CD4+CD25+CD127low regulatory cells was observed as compared with pre-transplant values between day 7 and 60; while in 1D patients there were not significant differences. Lower levels of regulatory CD4+ cells were observed up to d30 in 2D patients as compared with 1D patients: d7 2.52±2.62 vs 4.76±3.90%, p=0.046; d14 2.75±2.55 vs 5.08±5.17%, p=0.074 and d30 2.96±2.69 vs 5.61±3.78%, p=0.014. During the 6 months follow up there was no significant difference in the prevalence of acute cellular rejection in both groups. Conclusion In a 6 month post transplant immunemonitoring follow-up study of a single cohort, one-dose of Basiliximab maintained higher levels of regulatory cells compared to a conventional 2-dose regimen. Since CD4 regulatory cells are considered to have an important role against allograft rejection, this information should be taken into account. The potential role of this cellular immune monitoring to assist in clinical decision making should be further explored in future studies. Fondo de Investigación Sanitaria. Project FIS 1501472. With participation of FEDER funds. A way of making Europe.

Lower Rates of Death in Heart Recipients with Secondary Antibody Deficiency and Severe Infection After Therapy with Intravenous Immunoglobulin

Background Secondary antibody deficiency defined as IgG hypogammaglobulinemia (HGG) is a risk factor of severe infection in heart recipients. Single center studies (distinct induction protocols; various centers around the world); a multicenter prospective study; evaluation of reproducibility of IgG testing among centers and a metanalysis support the usefulness of this biomarker. Interventional studies evaluating the effect of the modification of the risk factor are necessary. We evaluated the impact of therapeutic intervention of intravenous immunoglobulin (IVIG) in heart recipients with severe infections and HGG on clinical outcomes. Methods Retrospective analysis of prospectively collected data of 233 patients in a single center. 91 patients that developed severe infections in the post-heart transplantation period and were found to have HGG (serum IgG<600 mg/dL), received non-specific 5% IVIG in addition to conventional antimicrobial therapy with the aims of contributing to control of infection (secondary prevention of re-infection) and normalization of IgG (IgG>750 mg/dL). IVIG was administered at a dose of 300-400 mg/kg/month up to three months after infections were resolved (negative bacterial culture or CMV DNAmia). 142 heart recipients from the same center that where not treated with IVIG, were analyzed as controls. Results Severe infections included non pneumonic bacterial infection (30%), bacterial pneumonia (18%), CMV disaese + bacterial infection (12%), CMV disease + severe fungal infection (12%). Mean IgG level at the time of infection was 481 mg/dL (198-599 mg/dL). Mean time to the first IVIG infusion was 65.4 days (7-180 days). Normalization of IgG levels was obtained in 75 of 91 patients (82.4%) after addition of IVIG. Both groups were comparable in terms of demographic and clinical variables. IVIG treated recipients disclosed a lower rate of death (p=0.006). In multivariate regression analysis, IVIG use (RH 0.27, 95%CI 0.09-0.82, p=0.017), use of non-cytolitic induction (anti-CD25) vs cytolitic (ATG) (RH 0.28, 95%CI 0.09-0.82, p=0.017) and number of episodes of acute rejection (per each increase, RH 2.17, 95% CI 1.25-3.78, p=0.0062) remained in the final regression model as protective factors and risk factors respectively. Conclusions Personalized immunoguided intervention of IVIG in heart recipients with severe infections and HGG is associated with a lower rate of death during long term follow-up after heart transplantation. A multicenter randomized clinical trial is in due course in Spain to further evaluate this new IVIG indication. Instituto de Salud Carlos III. Project FIS Clinical Trial EC11084. With participation of FEDER funds. A way of making Europe.

Mannose Binding Lectin (mbl2) Genotype Frequencies in Solid Organ Transplant Patients

Background Mannose-binding lectin (MBL) is a protein critical in the activation of the lectin complement pathway. Patients with wild-type and variant mbl2 genotypes have high or low concentrations of MBL protein, which have been associated to increase susceptibility to transplant rejection or infection, respectively. Objective Our objective was to determine mbl2 genotype frequencies in a cohort of solid organ transplant recipients and its relationship with clinical outcomes. Materials and Methods A retrospective observational study in a single center. DNA samples were obtained at the time of inclusion in the waiting list for solid organ trasplantation as part of an extended immunological analysis to assess the pre-transplant immunocompetence status of the patients (109 heart transplantation, 3 liver transplantation). DNA was extracted from 1.5-mL ethylene diamine tetraacetic acid–treated whole blood samples. Genotyping of MBL2 was done by a polymerase chain reaction (PCR)/sequence-based typing technique. MBL2 encompassing a region from the promoter to the end of exon 1 was obtained by PCR amplification. Results Frequencies of the MBL genotype in our patients were similar to those of other Spanish populations used as a reference: Low-expressing genotype 16 (14%), intermediate 30 (27%), high 66 (59%). We have confirmed a correlation of genotype and phenotype as patients with the intermediate and deficient mbl2 genotypes disclosed significantly lower concentrations of MBL protein. Patients with low-intermediate expressing genotypes had a higher prevalence of viral infections (p=0.004). Results Conclusion: Low-intermediate expressing genotype is a frequently expressed profile in the population that may predispose solid organ recipients to a greater susceptibility of viral infections. Under immunosuppressive clinical settings these genetic host factors might be associated with distinct clinical outcomes. The potential role of this genetic biomarker warrants further evaluation in prospective multicenter studies. Fondo de Investigación Sanitaria. Project FIS 1501472. With participation of FEDER funds. A way of making Europe.

Infections in patients after Berlin Heart®EXCOR assist device implantation

Berlin Heart® EXCOR devices (BHED) are ventricular assist devices (VAD) used mainly as a bridge to heart transplantation (HT) in pediatric population. The aim of our study is to report the infections diagnosed in adult patients undergoing a BHED implantation.

Refractory cardiogenic shock following idiopathic giant cell myocarditis in a 19-year-old woman

A 19-year-old woman with no medical history except for facial acne treated with tetracyclines during the previous year presented to the emergency room referring 1-week history of worsening muscle weakness, palpitations and exertional dyspnoea. Physical examination revealed a tachycardic (130 bpm), tachypnoeic and hypotensive (blood pressure 90/50 mm Hg) thin woman with fever of 38.5°C, rash and jugular vein distention. An ECG showed sinus tachycardia with 0.5 mm elevation of the ST segment in the anterior and inferior leads. In laboratory studies, she had leukocytosis with neutrophilia and eosinophilia and mild rise of troponin I (4.8 µg/l), creatine kinase (524 U/l) and transaminases (aspartate aminotransferase of 765 U/l and alanine aminotransferase of 658 U/l). An echocardiogram revealed severe biventricular dysfunction with global hypokinesia and circumferential mild pericardial effusion. Signs of heart failure were found on her chest x-ray. In this clinical situation, we treated her with dobutamine, but she started to develop sustained ventricular tachycardia and refractory hypotension during the following hours. Coronary angiography showed no coronary lesions and an intra-aortic balloon pump was inserted for counterpulsation. The next morning, a new transthoracic echocardiogram revealed a left ventricular ejection fraction of 10% with a dilated left ventricle. She underwent a right heart catheterisation with …