Graphene materials as 2D non-viral gene transfer vector platforms.

Advances in genomics and gene therapy could offer solutions to many diseases that remain incurable today, however, one of the critical reasons halting clinical progress is due to the difficulty in designing efficient and safe delivery vectors for the appropriate genetic cargo. Safety and large-scale production concerns counter-balance the high gene transfer efficiency achieved with viral vectors, while non-viral strategies have yet to become sufficiently efficient. The extraordinary physicochemical, optical and photothermal properties of graphene-based materials (GBMs) could offer two-dimensional components for the design of nucleic acid carrier systems. We discuss here such properties and their implications for the optimization of gene delivery. While the design of such vectors is still in its infancy, we provide here an exhaustive and up-to-date analysis of the studies that have explored GBMs as gene transfer vectors, focusing on the functionalization strategies followed to improve vector performance and on the biological effects attained.

Percutaneous Coronary Intervention VersusMyocardial Revascularization Surgery inMultivessel Coronary Artery Disease: Four-Year Followup.

INTRODUCTION: In Cuba, 29,939 deaths from ischemic heart disease were recorded in 2020. Myocardial revascularization surgery and percutaneous coronary intervention are well-established methods of treating patients with multivessel coronary artery disease. These methods can reduce overall deaths, but choosing the optimal strategy for treating left main coronary ischemia is a source of debate among specialists. OBJECTIVE: Estimate survival and major cardiac and cerebrovascular events in patients treated with percutaneous coronary intervention versus myocardial revascularization surgery and their relationships with pre-existing patients' clinical and angiographic characteristics. METHODS: We conducted a retrospective cohort study in 41 patients; 35 men and 6 women aged 40-85 years who had been diagnosed with multivessel coronary artery disease and treated with percutaneous coronary intervention (n = 17) or myocardial revascularization surgery (n = 24) at the Medical-Surgical Research Center in Havana, Cuba, in 2016. The main variable under consideration was the occurrence of major adverse cardiovascular events over a four-year period following these interventions. We collected clinical and angiographic characteristics, and used the Kaplan-Meier test to calculate survival curves. Survival probabilities were compared using the log-rank test. A value of p ⟨ 0.05 was considered statistically significant. The Cox proportional hazards model was used to estimate the hazard ratio, with 95% confidence intervals used for both procedures. RESULTS: There were a total of 20 major adverse cardiovascular events, 75% (15/20) of which occurred in patients who underwent percutaneous coronary intervention and 5% in patients who had myocardial revascularization surgery. The probability of survival was 70.6% in surgery and 37.5% in interventionism; p = 0.043; hazard ratio 1.58 (95% confidence interval 0.987-2.530), p = 0.047. The need to repeat a revascularization procedure was the only major cardiovascular event that showed significant differences between methods (log-rank p = 0.015), and was more frequent in percutaneous intervention. CONCLUSIONS: Myocardial revascularization surgery offers a better chance of survival than percutaneous coronary intervention. Major adverse cardiovascular events are more frequent in patients with coronary interventionism, due to the need to repeat revascularization.

Current Situation and Prognostic Evolution of Combined Heart-lung Transplantation in a European Union Country.

Background: This study aims to evaluate the entire experience in heart-lung transplantation (HLTx) in a country of the European Union with 47 million inhabitants according to the etiologies that motivated the procedure. Methods: A retrospective study on 1,751 consecutive transplants (HLTx: 78) was performed from 1990 to 2020 in two centers. Overall survival, adjusted for clinical profile and etiological subgroups, was compared. 7 subgroups were considered: 1) Cardiomyopathy with pulmonary hypertension (CM + PH). 2) Eisenmenger syndrome. 3) Congenital heart disease (CHD). 4) Idiopathic pulmonary arterial hypertension (IPAH). 5) Cystic fibrosis. 6) Chronic obstructive pulmonary disease (COPD)/Emphysema. 7) Diffuse interstitial lung disease (ILD). Results: Early mortality was 44% and that of the rest of the follow-up was 31%. There were differences between HTLx and HTx in survival, also comparing groups with a similar clinical profile with propensity score (p= 0.04). Median survival was low in CM + PH (18 days), ILD (29 days) and CHD (114 days), intermediate in Eisenmenger syndrome (600 days), and longer in IPAH, COPD/Emphysema and cystic fibrosis. Conclusion: HLTx has a high mortality. The etiological analysis is of the utmost interest to make the most of the organs and improve survival.

The APOA5-1131 T>C variant enhances the association between RBP4 and hypertriglyceridemia in diabetes.

BACKGROUND AND AIM: Type 2 diabetic patients have an increased prevalence of hypertriglyceridemia. RBP4 has been associated with insulin resistance and hypertriglyceridemia in obesity, the metabolic syndrome and type 2 diabetes. APOA5 is proposed to be a genetic modulator of triglycerides. The aim of this study was to evaluate the relationship between RBP4 plasma levels and lipid disturbances and to determine the impact of the APOA5-1131 T>C variant on this relationship in type 2 diabetic patients. METHODS AND RESULTS: A total of 165 type 2 diabetic patients were included in the study. RBP4 plasma levels and the APOA5-1131 T>C variant were determined and the complete lipid profile was assessed by sequential ultracentrifugation. RBP4 was positively correlated with triglyceride levels in plasma and with all the components of triglyceride-rich lipoproteins. Despite the fact that a statistically significant relationship between the APOA5 genetic variant and RBP4 plasma levels was not found, the hypertriglyceridemic effect of high RBP4 levels was enhanced by the presence of the APOA5-1131 T>C genetic variant. Correlation coefficients were 2-fold higher for TC carriers compared to TT carriers with regard to RBP4 plasma levels and all the components of triglyceride-rich lipoproteins. Those type 2 diabetic patients with high RBP4 plasma concentrations and who were TC carriers showed an increased incidence of hypertriglyceridemia (OR=7.46, P=0.010). CONCLUSION: RBP4 is associated with hypertriglyceridemia in type 2 diabetic patients. The RBP4 effect is conditioned by the presence of the APOA5-1131 T>C genetic variant.

p53 regulates the self-renewal and differentiation of neural precursors.

During embryo neurogenesis, neurons that originate from stem cells located in the forebrain subventricular zone (SVZ) continuously migrate to the olfactory bulb (OB). However, other authors describe the occurrence of resident stem cells in the OB. In the present work we report that the absence of tumor suppressor protein p53 increases the number of neurosphere-forming cells and the proliferation of stem cells derived from 13.5-day embryo OB. Interestingly, differentiation of p53 knockout-derived neurospheres was biased toward neuronal precursors, suggesting a role for p53 in the differentiation process. Moreover, we demonstrate the relevance of p53 in maintaining chromosomal stability in response to genotoxic insult. Finally, our data show that neurosphere stem cells are highly resistant to long-term epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) deprivation in a p53-independent fashion, and they preserve their differentiation potential. Thus, these data demonstrate that p53 controls the proliferation, chromosomal stability and differentiation pattern of embryonic mouse olfactory bulb stem cells.

What is the best biomarker for diagnosis of rejection in heart transplantation?

INTRODUCTION: Acute cellular rejection is a major cause of graft loss in heart transplantation (HT). Endomyocardial biopsy remains the gold standard for its diagnosis, but it is an invasive procedure not without risk. A proinflammatory state exists in rejection that could be assessed by determining plasma levels of inflammatory biomarkers. OBJECTIVE: To analyze the utility of various inflammatory markers, which is most important and what values best classify patients to diagnose rejection. MATERIALS AND METHODS: A prospective study in 123 consecutive cardiac transplant recipients was conducted from January 2002 to December 2006. Fibrinogen protein (Fgp) and function (Fgf), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and sialic acid (SA) determinations were performed at one, two, four, six, nine, and 12 months post-HT at the same time as biopsies. Coronary arteriography and intravascular ultrasound were performed on the first and last follow-up visits. Heart-lung transplants, retransplants, pediatric transplants, patients who died in the first month, and patients who refused consent were excluded. Also excluded were determinations that coincided with renal dysfunction, active infection, hemodynamic instability, or a non-evaluable biopsy. The final analysis included 79 patients and 294 determinations. The correlation between the levels of these biomarkers and the presence of rejection in the biopsy (> or = ISHLT grade 3) was studied. RESULTS: We did not find significant differences in the values of any of the markers analyzed on the six follow-up visits. Only CRP showed significant and sustained differences between the two groups (with and without rejection) from the second follow-up visit (month 2). The area under the curve showed significant differences in Fgp (0.614, p = 0.013), Fgf (0.585, p = 0.05), TNF-alpha (0.605, p = 0.02), SA (0.637, p = 0.002) and mainly CRP (0.765, p = 0.0001). CRP levels below 0.87 mg/dL ruled out rejection with a specificity of 90%. CONCLUSIONS: Among the inflammatory markers analyzed, CRP was the most useful parameter for non-invasive screening of acute cellular rejection in the first year post-HT.

Molecular Alterations of Nucleocytoplasmic Transport in Patients on the Heart Transplantation Waiting List and Its Correlation With the Severity and Etiology of Heart Failure.

OBJECTIVES: To evaluate whether the levels of some molecules implicated in nucleocytoplasmic transport in human cardiomyocytes are related to the severity of heart failure (HF) in patients on the heart transplantation (HT) waiting list, and to determine whether there is a differential pattern of molecular alteration between ischemic cardiomyopathy (ICM) and non-ischemic dilated cardiomyopathy (DCM). METHODS: Sixty-three blood samples collected before HT were analyzed to identify the levels of IMPORTIN5 (IMP5); IMPORTINalpha2; ATPaseCaTransp (ATPCa); NUCLEOPORIN153kDa (Nup153); NUCLEOPORIN160kDa (Nup160); RANGTPaseAP1 (RanGAP1) and EXPORTIN4 (EXP4). These data were then compared between patients with advanced HF with or without the need for ventricular support with extracorporeal membrane oxygenation (ECMO) as a bridge for HT, as well as between patients with non-ischemic DCM and patients with ICM. RESULTS: Thirty-three patients had ICM, 26 had non-ischemic DCM, and 4 had heart disease. Seventeen patients required ventricular assistance as a bridge to HT. The levels of ATPCa, RanGAP1, and IMP5 were significantly higher in patients with ECMO, while EXP4 was significantly higher in patients without ECMO. Patients with DCM showed higher levels of IMP5, RanGAP1, and Nup153 than those with ICM. CONCLUSION: Patients with advanced HF in critical condition (with ECMO as a bridge for HT) presented with significantly higher levels of ATPCa, RanGAP1, and IMP5, while patients with DCM had significantly higher levels of RanGAP1, IMP5, and Nup153. It remains to be clarified whether the determination of these molecules would facilitate the early identification of this group or if their alteration occurs as consequence of circulatory support with ECMO.

Analysis of heart rate turbulence in advanced heart failure and heart transplantation patients.

OBJECTIVE: The objective of this study was to describe heart rate turbulence (HRT) in advanced heart failure (HF) patients and in a group of patients who underwent heart transplantation (HT). MATERIALS AND METHODS: We performed 24-hour Holter recordings in 20 patients with advanced HF referred to our hospital for HT, including 16 males of overall mean age of 44 +/- 13 years and with a mean ejection fraction (EF) 21 +/- 7%. An additional set of recordings was obtained in a second group of 27 patients who had already undergone HT, including of 21 males of overall mean age of 47 +/- 14 years. We recorded the number of premature ventricular contractions (PVCs), mean heart rate (MHR), and 2 parameters of HRT-turbulence onset (TO) and turbulence slope (TS). RESULTS: Patients with HT showed a low density of premature ventricular complexes, in contrast to patients in the advanced HF group. For this reason, HRT could only be analyzed in 15 of the patients with advanced HF (66%) and in 10 of the patients who underwent HT (37%). MHR was 77 +/- 10 bpm in the advanced HF group and 90 +/- 10 bpm in the HT group. In both groups, TO and TS showed highly attenuated values. CONCLUSIONS: Patients with advanced HF showed a high number of PVCs with attenuated HRT parameters, reflecting increased circulating catecholamine levels and decreased response of the autonomic nervous system. Patients who underwent HT showed elevated MHRs, a small number of PVCs, and attenuated HRT values, as corresponds to a denervated heart.

Effect of clinical trials on survival after heart transplantation.

UNLABELLED: The application of clinical trials (CTs) to daily practice is based on the assumption that the patients included in these trials are similar to those seen on a daily basis. We performed a retrospective study to evaluate patient survival depending on whether they were included in a CT. We studied 217 patients who underwent heart transplantation (HT) between January 2000 and September 2006. We excluded patients who received combination transplants, those who underwent repeat HT, and pediatric patients who underwent HT. In total, 54 patients were included in a CT and 163 were not (NCT). The statistical tests included the t test, the chi(2) test and the Kaplan-Meier method. RESULTS: Patients in the NCT group were in worse condition at HT, with a greater percentage of inotropic treatments pre-HT (36% vs 17%; P = .005), emergency transplants procedures (30% vs 13%; P = .01), and worse functional status pre-HT (P = .03). The NCT group exhibited lower survival (80.37% vs 87.04%; P = 0.13, log-rank test). There were no significant differences in the other analyzed variables. CONCLUSIONS: Patients included in CTs tend to have better long-term survival rates, for several reasons: patients in the CT group were more stable at HT (selection bias), and the close follow-up of patients in CTs makes it more likely that any complication will be detected and treated early (follow-up bias).

Randomized prospective study of the evolution of renal function depending on the anticalcineurin used.

BACKGROUND: Renal failure is one of the primary medium- to long-term morbidities in heart transplant (HT) recipients. To a great extent, this renal deterioration is associated with calcineurin inhibitors, primarily cyclosporine A (CsA). It has been suggested that tacrolimus provides better renal function in these patients. We assessed the medium-term evolution of renal function depending on the calcineurin inhibitor used after HT. PATIENTS AND METHOD: We assessed 40 consecutive HT recipients over one year. Patients were randomized to receive CsA (n = 20) or tacrolimus (n = 20) in combination with mycophenolate mofetil (1 g/12 h) and deflazacort in decreasing dosages. We analyzed demographic variables before HT, creatinine values before and six months after HT and incidence of acute rejection. RESULTS: No demographic, clinical, or analytical differences were observed were between the two groups before HT. Repeated measures analysis of variance of creatinine values showed no significant differences between the two groups (P = .98). Furthermore, no differences were observed in either the incidence of rejection (P = .02) or rejection-free survival (P = .14). CONCLUSION: There seems to be no difference in efficacy profile and renal tolerability between CsA and tacrolimus therapy during the first months after HT.

Tolerance profile of the proliferation signal inhibitors everolimus and sirolimus in heart transplantation.

INTRODUCTION: The side effects of proliferation signal inhibitors (PSIs) have been characterized as a class. However, it would be convenient to assess them according to the molecule. OBJECTIVE: To assess prospectively the tolerance of PSIs among heart transplant (HT) patients. PATIENTS AND METHODS: We studied 56 HT patients who sequentially received PSIs to either withdraw (77%) or reduce the dosage of a calcineurin inhibitor; 42 received everolimus (EVE) and 14 sirolimus (SRL). We analyzed the demographic variables, side effects, and need to withdraw the drug during a median follow-up period of 365 days. RESULTS: No differences between groups were observed upon analysis of the clinical and demographic variables when the treatment was changed owing to renal dysfunction (67%) or tumor (32%). No difference between groups was observed over the follow-up period (P = .28). Infection was the most common side effect, 28.6%: EVE, 14.3% versus SRL, 71.4% (P < .0001). Edema occurred in 26.8% of patients: EVE, 14.3% versus SRL, 64.3% (P = .001); diarrhea in 5.4% of patients: EVE, 2.4% versus SRL, 14.3% (P = .15). Treatment was withdrawn in 23.2% of the patients due to intolerance: EVE, 11.9% versus SRL, 57.1% (P < .0001). EVE showed significantly better survival without edema or infections or used for drug withdrawal upon Kaplan-Meier analysis, (P = .01; P = .0005; P = .0097). Only SRL use was shown to be an independent predictor of side effects. CONCLUSION: Edema and infections are the main problems caused by PSIs. EVE may display a better tolerance profile than SRL.

Support program for heart transplant patients: initial experience.

INTRODUCTION: Trials of education and support in heart failure patients have shown an improvement in patient prognosis with favorable results in cost-benefit analysis. OBJECTIVES: To assess the impact of a telephone support program for heart transplant patients during the first year after transplantation. PATIENTS AND METHODS: We analyzed 30 consecutive heart transplant patients at our institution, who were randomized to either a standard care group or a group with the additional possibility of direct telephone contact with a cardiologist. We analyzed the time employed answering the calls, the reasons for consultation, and the number of hospital trips avoided. RESULTS: Among the total sample, 15 patients were assigned to the intervention program. Over 194 +/- 103 days, we received 28 calls. The mean call duration was 10.2 +/- 3.9 minutes, with 39.3% of the consultations concerning medication dosages 28.6% lifestyle issues, 25% infectious symptoms, and the remaining 7%, medication side effects. Medication readjustments were made in 33% of the calls; 10.7% of the calls, all for infectious symptoms, required direct medical consultation. CONCLUSION: Telephone support may be useful to improve therapeutic compliance, adjust the medications, and avoid treatment errors, as well as detect early complications during follow-up. In addition, it may avoid unnecessary medical visits.

Utility of oral valganciclovir for cytomegalovirus prophylaxis: does it improve treatment compliance?

INTRODUCTION: Cytomegalovirus (CMV) infection is a significant cause of morbidity and mortality among heart transplant (HT) patients. Various prophylactic and preemptive treatment regimens have been used for its prevention. We sought to assess the impact of oral valganciclovir on CMV prophylaxis in HT patients. PATIENTS AND METHODS: A retrospective analysis of 536 consecutive HT patients at our institution allowed selection of subjects eligible for prophylaxis based on CMV serology (donor positive/recipient negative). Treatment compliance, rates of preemptive therapy and treatment for CMV disease were assessed according to prophylactic drug use. If the indication was present, treatment was considered to have been performed. RESULTS: Among 536 patients, 9.8% (n = 53) were eligible for prophylaxis. Seventeen patients (33%) received valganciclovir, with a compliance rate of 94.1%. The remaining 68% received prophylaxis mainly with IV. ganciclovir (5 mg/kg) during their hospital stay followed by oral ganciclovir, with a compliance rate of 57.1% (P = .01). No differences were observed when we analyzed the need for preemptive therapy (0 vs 7%; P = .28) or for treatment of systemic or organ-specific infection (6.3 vs 0%; 6.3 vs 14%, respectively; P = .8). CONCLUSION: Oral valganciclovir facilitated treatment compliance in prophylaxis for CMV without being inferior to other prophylactic therapies.

Effect of circulatory assistance on premature death and long-term prognosis.

BACKGROUND: Patients undergoing urgent heart transplantation (HT) have a poorer prognosis and more long-term complications. The objective of this study was to compare the preoperative course in patients undergoing urgent HT according to the need for preoperative intra-aortic balloon counterpulsation (IABP). MATERIALS AND METHODS: We studied 102 consecutive patients including 23 patients with IABP who underwent urgent HT between January 2000 and September 2006. We excluded patients who received combination transplants, those who underwent repeat HT, and pediatric patients who underwent HT. The statistical methods used were the t test for quantitative variables and the chi(2) test for qualitative variables. A logistic regression model was constructed to assess the possible relationship between IABP and other variables on premature death within 30 days after HT. RESULTS: Mean (SD) patient-age was 50 (10) years. No significant differences were observed in baseline characteristics between the IABP and the non-IAPB groups. The IABP patient group had higher rates of acute graft failure (45.5% vs 35.4%; P = .46) and premature death (18.8% vs 14.8%; P = .67) and shorter long-term survival (40.6 [34.9] vs 54.5 [43.7] mo; P = .30). Multivariate analysis demonstrated no association between the need for IABP and increased frequency of premature death. CONCLUSIONS: Use of IABP is not associated with premature or late death. We recommend use of IABP in patients with acute decompensated heart failure to stabilize them before HT.

Effect of hypertension, diabetes, and smoking on development of renal dysfunction after heart transplantation.

BACKGROUND: Renal dysfunction is a serious problem after heart transplantation (HT). The objective of this study was to determine the cardiovascular risk factors associated with medium- to long-term dysfunction after HT. MATERIALS AND METHODS: We studied 247 consecutive patients who underwent HT between January 2000 and September 2006 who survived for at least 6 months. We excluded patients receiving combination transplants, those undergoing repeat HT, and pediatric patients undergoing HT. Mean (SD) follow-up was 72 (42) months. We defined renal dysfunction as serum creatinine concentration greater than 1.4 mg/dL during follow-up. Patients were considered to be smokers if they had smoked during the six months before HT, to have hypertension if they required drugs for blood pressure control, and to have diabetes if they required insulin therapy. Statistical tests included the t test and the chi(2) tests. We performed Cox regression analysis using significant or nearly significant values in the univariate analysis. RESULTS: Mean (SD) age of the patients who underwent HT was 52 (10) years, and 217 (87.9%) were men. Renal dysfunction was detected during follow-up in 135 (54.5%) patients. The significant variables at univariate analysis were smoking (61.4% vs. 43.2%; P = .01) and previous renal dysfunction (94.1% vs 52.7%; P = .001). Nearly significant variables were the presence of hypertension before HT (63.8% vs 51.1%; P = .09) and after HT (58.2% vs 44.8%; P = .082). At multivariate analysis, pre-HT smoking and previous renal dysfunction were significant correlates (P = .04 and P = .01, respectively). CONCLUSIONS: Renal dysfunction is common after HT. In our analysis, the best predictors were pre-HT dysfunction and smoking. Less important factors were advanced age and post-HT hypertension.

Hypertension after heart transplantation: predictive factors and number and classes of drugs for its management.

BACKGROUND: This study was performed to determine the factors that cause arterial hypertension after heart transplantation (HT) and the drugs used in its management. MATERIALS AND METHODS: We studied 247 consecutive patients who had undergone HT between 2000 and 2006 and who survived for at least 6 months. We excluded patients who received combination transplants, those who underwent repeat transplantation, and pediatric patients who had received transplants. Hypertension was defined as the need to use drugs for its control. Renal dysfunction was defined as serum creatinine concentration greater than 1.4 mg/dL, and diabetes as the need for an antidiabetes drug for its control. Statistical analyses were performed using the t test, the chi(2) test, and Cox regression. RESULTS: Mean (SD) patient age was 52 (10) years, and 87.4% of the patients were men. Follow-up was 72 (42) months. Hypertension was present in 33.3% of patients before HT and in 71.1% at some time after HT. The number of drugs used to control hypertension was 1.3 (0.5); one drug was used in 72.9% of patients. The most often used single class of drugs were calcium channel blockers (63.2%), followed by angiotensin-converting enzyme inhibitors (20%), and angiotensin receptor blockers (15.8%). Only pre-HT hypertension was significantly associated with greater use of antihypertensive drugs post-HT (mean [SD], 1.48 [0.65] vs 1.22 [0.41]; P = .005). At univariate analysis, only pre-HT hypertension was associated with the presence of post-HT hypertension (80.5% vs 65.5%; P = .02). At Cox regression analysis, recipient age (P = .02) and pre-HT hypertension (P = .004) were associated with post-HT hypertension. CONCLUSIONS: Hypertension is common after HT; however, in most patients, it can be controlled with a single antihypertensive agent. The most important factors in the development of hypertension are the presence of pre-HT hypertension and advanced age.

Influence of traditional cardiovascular risk factors in the recipient on the development of cardiac allograft vasculopathy after heart transplantation.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is the leading cause of death heart transplant (HT) recipients after the first year. We assessed the influence of cardiovascular risk factors (CVRFs) in HT recipients on the development of CAV after 1 year of follow-up. MATERIALS AND METHODS: From 2001 to 2005, we studied 72 patients who received a HT and survived for at least 1 years. All patients underwent coronary arteriography and intravascular ultrasonography at 1 year after HT. Cardiac allograft vasculopathy was defined as intimal proliferation of 0.5 mm or more. The analyzed CVRFs were age, sex, body mass index, diabetes mellitus, hypertension, dyslipidemia, and smoking. We also considered the heart disease that was the reason for HT. The statistical tests used in the univariate analysis were the t and chi(2) tests. Logistic regression was performed with the variables obtained at univariate analysis. RESULTS: Mean (SD) recipient age at HT was 51 (9) years. Eighty patients (90.5%) were men. Dyslipidemia was significantly associated with a greater incidence of CAV at 1 year (68.3% vs 41.9%; P = .03). Ischemia, as opposed to all other causes, was also significantly associated with CAV (69.4% vs 44.4%; P = .03). Older age, hypertension, smoking history, and high body mass index were associated with a higher incidence of CAV, albeit without statistical significance. At multivariate analysis, dyslipidemia was the most significant CVRF (P = .045) for the development of CAV. CONCLUSIONS: Recipient dyslipidemia is a risk factor for the development of CAV in HT. The remaining traditional CVRFs are more weakly associated with CAV. After HT close monitoring of recipients with pretransplantation CVRFs is essential for early detection of CAV.

Correlation between beta-adrenoceptors and G-protein-coupled receptor kinases in pretransplantation heart failure.

INTRODUCTION: Prolonged catecholamine overstimulation of the myocardium in chronic heart failure causes a reduction in the number and functionality of beta1-adrenoceptors (beta1-AR) of the heart. Desensitization of beta1-AR is mediated by their phosphorylation by a group of cytosolic kinases (G-protein-coupled receptor kinases GRK). In advanced heart failure, an increase in GRK levels associated with the severity of the disease has been observed. OBJECTIVE: The objective of this study was to analyze messenger RNA (mRNA) levels of beta1-AR in the myocardium of patients who underwent transplantation for advanced heart failure and their correlation with expression of the major cardiac isoenzymes of GRK. MATERIALS AND METHODS: Myocardial tissue samples were obtained from the left ventricles of 14 explanted hearts of patients who underwent transplantation for dilated (n = 7) and ischemic (n = 7) cardiomyopathy. RT-PCR techniques were used to analyze mRNA levels of beta1-AR and the isoenzymes GRK2, GRK3, and GRK5. RESULTS: We observed a significant correlation between beta1-AR and the 3 subtypes of GRK (R(2) = 0.668, 0.71, and 0.318, respectively). CONCLUSIONS: In patients with advanced heart failure pretransplantation, we observed a significant correlation between beta1-AR and GRK2 and GRK3 levels. GRK5, the subtype predominantly expressed in the myocardium, showed a lesser correlation with beta1-AR levels.

Clinical variables associated with the presence of inflammatory infiltrates in patients with dilated cardiomyopathy undergoing heart transplantation.

INTRODUCTION: Idiopathic dilated cardiomyopathy (DCM) is, together with ischemic heart disease, the major cause of end-stage heart failure leading to heart transplantation. However, an unknown percentage of patients with this diagnosis has inflammatory foci found in the histopathological study of the explanted heart. This fact suggests an undetected process of acute myocarditis as the cause of cardiac dysfunction. OBJECTIVE: The objective of this study was to identify clinical and echocardiographic variables related to the presence of myocardial infiltrates, as a potential guide to determine which patients should undergo endomyocardial biopsy in DCM. MATERIALS AND METHODS: We retrospectively analyzed 161 patients who underwent heart transplantation with a diagnosis of DCM between 1987 and 2007. The presence of inflammatory infiltrates was considered significant when the histopathological study of tissue blocks from the left ventricle showed 1 or more foci per cm(2) of perivascular or interstitial mononuclear or polymorphonuclear cells, whether or not in the presence of cytolysis. RESULTS: Seventeen patients (11%) had these inflammatory histological findings; of them, 6 (35%) showed preponderance of eosinophils and 7 (41%) showed areas of cytolysis. The DCM group with inflammatory infiltrates showed significant differences in terms of younger age (45 +/- 15 vs 50 +/- 11 years; P < .01) and smaller ventricular diameters (P < .05). Male gender was more frequent in this group, and the patients had a poorer clinical status and greater dependence on inotropic drugs. CONCLUSIONS: Inflammatory infiltrates are frequently present in DCM explanted hearts. Although there are no relevant clinical variables to identify subclinical myocarditis, these patients are younger and have smaller ventricular diameters and poorer functional status at the time of transplantation.