Increased risk factors associated with lower BMD in antiretroviral-therapy-naïve HIV-infected adult male.

BACKGROUND: Low BMD (bone mineral density) has been described as a non-AIDS (Acquired Immune Deficiency Syndrome)-related event in HIV (human immunodeficiency virus)-patients but it is poorly studied in young HIV-infected men who have received no previous antiretroviral therapy. METHODS: A cross-sectional study of 245 naïve-HIV-infected men over 21 and under 50 years old who voluntary attended the Infectious Disease Division appointment in Hospital Fundación Jimenez Díaz in Madrid, from January 1st, 2014 to September 30th, 2017. All subjects underwent a baseline DXA scan (dual energy x-ray absorptiometry) performed prior to start antiretroviral treatment. Further, all patients who started treatment between May 1st and September 30th, 2017 were invited to participate in a substudy on bone mineral metabolism. All the information was collected through clinical history and complementary questionnaire. RESULTS: The mean age was 36.4 years, been 68% Caucasian, 29.3% Latin American and 2.7% African race. At the time of diagnosis, 91% of patients had stage-A (median CD4+ T-cell 481cells/µL, IQR, 320-659). 10% had a count below 200 CD4 cells/µL, and 40% had a CD4/CD8 cell-count-ratio below 0.4. Regarding lifestyle and risk factors, 14.1% presented underweight, 36.1% were not engage in any regular exercise, 51.9% were active smokers and 35.3% reported drug use. Low levels of vitamin D were seen in 87.6% of the study participants. Low BMD (Z-score <- 2.0) was found in 22.8% of the patients. It was only observed a significant association of Z-score in lumbar spine (LS) with CD8 and the CD4/CD8 ratio, and with alcohol for femoral neck (FN) measurement. CONCLUSIONS: We find prevalence of increased bone involvement among naïve HIV-infected men under 50 years old. Further studies are necessary to evaluate if changes in actual guidelines are needed to assess BMD measurements in HIV-infected adult male patients under 50.

Adenosine Deaminase as a Biomarker of Tenofovir Mediated Inflammation in Naïve HIV Patients.

Plasma levels of adenosine deaminase (ADA), an enzyme that deaminates adenosine to inosine, are increased during inflammation. An increase in ADA activity occurs with lower human immunodeficiency virus (HIV) viral load and higher CD4+ T cell counts. We aimed to investigate the role of plasma ADA as a biomarker of inflammation in treatment-naïve HIV patients who received tenofovir or another nucleoside analog for comparison. Ninety-two treatment-naïve patients were included in the study and grouped by treatment, i.e., tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF) or Triumeq. ADA activity was measured in plasma and cytokines were analyzed by MILLIPLEX® MAP-Luminex® Technology. Plasma concentration of monocytes and neutrophils was measured at 0, 3, and 12 months post-treatment. Treatment-naïve HIV patients had increased ADA concentrations (over 15 U/L) that decreased after treatment with TAF and Triumeq, though this did not occur in TDF-treated patients. However, all groups exhibited a pro-inflammatory systemic profile at 12 months of treatment. Plasma GM-CSF levels decreased after 12 months of treatment in the TDF group, with a concomitant decrease in blood monocyte count, and a negative correlation with ADA values was found. In conclusion, ADA levels may be modulated by antiretroviral therapy in HIV patients, possibly affecting inflammatory status.

Microbiological and Cellular Evaluation of a Fluorine-Phosphorus-Doped Titanium Alloy, a Novel Antibacterial and Osteostimulatory Biomaterial with Potential Applications in Orthopedic Surgery.

Joint prosthesis failure is mainly related to aseptic loosening and prosthetic joint infections, both of which are associated with high morbidity and substantial costs for patients and health systems. The development of a biomaterial that is capable of stimulating bone growth while minimizing bacterial adhesion would reduce the incidence of prosthetic failure. We report antibacterial and osteostimulatory effects in a novel fluorine-phosphorus (F-P)-doped TiO2 oxide film grown on Ti-6Al-4V alloy with a nanostructure of bottle-shaped nanotubes (bNT) using five bacterial species (Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia) and MCT3T3-E1 osteoblastic cells. The interaction between the bacteria and bNT Ti-6Al-4V was complex, as the adhesion of four bacterial species decreased (two staphylococcus species, E. coli, and S. maltophilia), and the viability of staphylococci and S. maltophilia also decreased because of the aluminum (Al) released by bNT Ti-6Al-4V. This released Al can be recruited by the bacteria through siderophores and was retained only by the Gram-negative bacteria tested. P. aeruginosa showed higher adhesion on bNT Ti-6Al-4V than on chemically polished (CP) samples of Ti-6Al-4V alloy and an ability to mobilize Al from bNT Ti-6Al-4V. The cell adhesion and proliferation of MCT3T3-E1 osteoblastic cells significantly increased at 48 and 168 h, as did the matrix mineralization of these cells and the gene expression levels of three of the most important markers related to bone differentiation. According to our results, the bNT Ti-6Al-4V alloy could have clinical application, preventing infection and stimulating bone growth and thus preventing the two main causes of joint prosthesis failure.IMPORTANCE This work evaluates F-P-doped bNT Ti-6Al-4V from microbiological and cellular approaches. The bacterial results highlight that the antibacterial ability of bNT Ti-6Al-4V is the result of a combination of antiadhesive and bactericidal effects exerted by Al released from the alloy. The cell results highlight that F-P bNT Ti-6Al-4V alloy increases osseointegration due to modification of the chemical composition of the alloy resulting from P incorporation and not due to the nanostructure, as reported previously. A key finding was the detection of Al release from inside the bNT Ti-6Al-4V nanostructures, a result of the nanostructure growth during the anodizing process that is in part responsible for its bactericidal effect.

ß2- and ß1-Adrenoceptor Expression Exhibits a Common Regulatory Pattern With GRK2 and GRK5 in Human and Animal Models of Cardiovascular Diseases.

To explore if genic expression of ß(1)- or ß(2)-adrenoceptors (ARs) exhibits a common regulatory pattern with G protein-coupled receptor kinase (GRK) 2, GRK3, or GRK5 expression, we determined messenger RNA levels for these genes in different tissues from human and animal models of cardiovascular disease. We measured genic expression by qRT polymerase chain reaction in the left and right ventricles or peripheral blood mononuclear cells from healthy (n = 21), hypertensive (n = 20), heart failure (n = 24), and heart transplanted patients (n = 17) or in left ventricle, peripheral blood mononuclear cells, and kidney from spontaneously hypertensive rats or L-N-methyl-arginine-induced hypertensive rats and their respective controls (n = 4-5). In diseased versus healthy subjects and rats, parallel changes in messenger RNA levels of GRK2 and ß(2)-AR or GRK5 and ß(1)-AR were observed in each territory. Therefore, without excluding other regulatory mechanisms, the parallelism observed suggests a common regulatory pattern for the ß(1)-AR/GRK5 and ß(2)-AR/GRK2 genes, which is independent of cellular type or pathology. This highlights the need to focus not only on GRKs but also on ß(1)- or ß(2)-AR changes to completely understand the involvement of ß-AR/GRK pathways in cardiovascular diseases.

Decreased clinical performance in TGA-ASO patients after RVOT interventions; a multicenter European collaboration.

BACKGROUND: In patients with transposition of the great arteries and an arterial switch operation (TGA-ASO) right ventricular outflow tract (RVOT) obstruction is a common complication requiring one or more RVOT interventions. OBJECTIVES: We aimed to assess cardiopulmonary exercise capacity and right ventricular function in patients stratified for type of RVOT intervention. METHODS: TGA-ASO patients (≥16 years) were stratified by type of RVOT intervention. The following outcome parameters were included: predicted (%) peak oxygen uptake (peak VO2), tricuspid annular plane systolic excursion (TAPSE), tricuspid Lateral Annular Systolic Velocity (TV S'), right ventricle (RV)-arterial coupling (defined as TAPSE/RV systolic pressure ratio), and N-terminal proBNP (NT-proBNP). RESULTS: 447 TGA patients with a mean age of 25.0 (interquartile range (IQR) 21-29) years were included. Patients without previous RVOT intervention (n = 338, 76%) had a significantly higher predicted peak VO2 (78.0 ± 17.4%) compared to patients with single approach catheter-based RVOT intervention (73.7 ± 12.7%), single approach surgical RVOT intervention (73.8 ± 28.1%), and patients with multiple approach RVOT intervention (66.2 ± 14.0%, p = 0.021). RV-arterial coupling was found to be significantly lower in patients with prior catheter-based and/or surgical RVOT intervention compared to patients without any RVOT intervention (p = 0.029). CONCLUSIONS: TGA patients after a successful arterial switch repair have a decreased exercise capacity. A considerable amount of TGA patients with either catheter or surgical RVOT intervention perform significantly worse compared to patients without RVOT interventions.

Urinary TNF-α as a potential biomarker for chronic primary low back pain.

Introduction: Over two thirds of individuals with low back pain (LBP) may experience recurrent or persistent symptoms in the long term. Yet, current data do not allow to predict who will develop chronic low back pain and who will recover from an acute episode. Elevated serum levels of the proinflammatory cytokine tumor necrosis factor-α (TNF-α) have been associated with poor recovery and persistent pain following an acute episode of LBP. Inflammatory cytokines may also mediate mechanisms involved in nociplastic pain, and thus, have significant implications in chronic primary low back pain (CPLBP). Methods: This study aimed to investigate the potential of urinary TNF-α levels for predicting outcomes and characterizing clinical features of CPLBP patients. Twenty-four patients with CPLBP and 24 sex- and age-matched asymptomatic controls were recruited. Urinary TNF-α concentrations were measured at baseline and after 4 weeks, during which CPLBP patients underwent spinal manipulative therapy (SMT). Results: Concentrations of TNF-α were found to be elevated in baseline urine samples of CPLBP patients compared to asymptomatic controls. Moreover, these values differed among patients depending on their pain trajectory. Patients with persistent pain showed higher levels of TNF-α, when compared to those with episodic CPLBP. Furthermore, baseline TNF-α concentrations and their changes after 4 weeks predicted alterations in pain intensity and disability following SMT in patients with CPLBP. Discussion: These findings warrant further research on the potential use of urinary TNF-α concentrations as a prognostic biomarker for CPLBP.

A network analysis on biopsychosocial factors and pain-related outcomes assessed during a COVID-19 lockdown.

Psychological stress, social isolation, physical inactivity, and reduced access to care during lockdowns throughout a pandemic negatively impact pain and function. In the context of the first COVID-19 lockdown in Spain, we aimed to investigate how different biopsychosocial factors influence chiropractic patients' pain-related outcomes and vice-versa. A total of 648 chiropractic patients completed online questionnaires including variables from the following categories: demographics, pain outcomes, pain beliefs, impact of the COVID-19 pandemic, stress/anxiety and self-efficacy. Twenty-eight variables were considered in a cross-sectional network analysis to examine bidirectional associations between biopsychosocial factors and pain outcomes. Subgroup analyses were conducted to estimate differences according to gender and symptom duration. The greatest associations were observed between pain duration and pain evolution during lockdown. Participants' age, pain symptoms' evolution during lockdown, and generalized anxiety were the variables with the strongest influence over the whole network. Negative emotions evoked by the pandemic were indirectly associated with pain outcomes, possibly via pain catastrophizing. The network structure of patients reporting acute pain showed important differences when compared to patients with chronic pain. These findings will contribute to identify which factors explain the deleterious effects of both the pandemic and the restrictions on patients living with pain.

Presence of Tumor Necrosis Factor-Alpha in Urine Samples of Patients With Chronic Low Back Pain Undergoing Chiropractic Care: Preliminary Findings From a Prospective Cohort Study.

Background and aims: Low back pain is the leading cause of years lived with disability worldwide. Chiropractors employ different interventions to treat low back pain, including spinal manipulative therapy, although the mechanisms through which chiropractic care improves low back pain are still unclear. Clinical research and animal models suggest that spinal manipulation might modulate plasma levels of inflammatory cytokines, which have been involved in different stages of low back pain. More specifically, serum levels of Tumor Necrosis Factor-alpha (TNF-α) have been found to be elevated in patients with chronic low back pain. We aimed to investigate whether urine from chronic low back pain patients could be an appropriate medium to measure concentrations of TNF-α and to examine possible changes in its levels associated to chiropractic care. Methods: Urine samples were collected from 24 patients with chronic low back pain and TNF-α levels were analyzed by ELISA before and after 4-6 weeks of care compared to a reference value obtained from 5 healthy control subjects, by means of a Welch's t-test. Simultaneously, pain intensity and disability were also evaluated before and after care. Paired t-tests were used to compare mean pre and post urinary concentrations of TNF-α and clinical outcomes. Results: Significantly higher baseline levels of urinary TNF-α were observed in chronic low back pain patients when compared to our reference value (p < 0.001), which were significantly lower after the period of chiropractic treatment (p = 0.03). Moreover, these changes were accompanied by a significant reduction in pain and disability (both p < 0.001). However, levels of urinary TNF-α were not correlated with pain intensity nor disability. Conclusion: These results suggest that urine could be a good milieu to assess TNF-α changes, with potential clinical implications for the management of chronic low back pain.

Pain catastrophizing mediates rapid benefits of accessing in-person chiropractic care during the COVID-19 lockdown.

BACKGROUND: In March 2020, the COVID-19 pandemic forced the Spanish government to declare a state of emergency. A stringent lockdown was enforced, restricting access to healthcare services, including chiropractic. Reduced access to care provision in combination with psychological stress, social isolation and physical inactivity during the lockdown were shown to negatively influence pain conditions. However, data on strategies to mitigate the impact of the pandemic on these conditions are lacking. METHODS: Upon easing of restrictions in May 2020, 51 chiropractic clinics throughout Spain pseudo-randomly invited patients, recruiting a total of 385 participants. During a 14-day period, participants were exposed to in-person chiropractic care in either one (n = 177) or multiple encounters (n = 109) or to no care (n = 99). The effects of access to chiropractic care on patients' pain-related and psychological outcomes were assessed online through validated self-reported questionnaires before and after the period of care. Coprimary outcomes included pain intensity, pain interference and pain cognitions. RESULTS: When comparing to participants without access to care, pain intensity and interference were significantly decreased at follow-up, irrespective of the number of encounters. Kinesiophobia was also significantly reduced at follow-up, though only after multiple encounters. The relationship between fear of movement, changes in pain intensity and interference was mediated by catastrophizing. CONCLUSION: Access to in-person chiropractic care may provide pain relief, associated with reductions in interference and pain cognitions. Prioritizing in-person care for patients with maladaptive pain cognitions may help dampen the detrimental consequences of the pandemic on physical and psychological well-being.

Cardiac magnetic resonance imaging at 1.5 T in patients with cardiac rhythm devices.

AIMS: Recent studies suggest that non-cardiac magnetic resonance imaging (MRI) scanning can be performed safely in selected cardiac rhythm device patients. However, little is known about the safety of performing specific cardiac MRI in this setting. We sought to determine the feasibility of cardiac MRI in patients with pacemakers (PMs) or implantable cardioverter-defibrillators (ICDs). METHODS AND RESULTS: Thirty-eight patients underwent a total of 39 (8 ICDs and 31 PM) cardiac MRI examinations at 1.5 T using usual protocols without specific absorption rate (SAR) restrictions. Nine PM-dependent patients were included. All devices were interrogated before and immediately after MRI. During the scan, pacing mode was programmed to asynchronous for PM-dependent patients whereas ICDs were programmed to a monitor-only mode. All devices were functioning appropriately after cardiac MRI. Comparison of device parameters obtained before and immediately after MRI revealed no significant changes in pacing threshold, lead impedance, battery status, or sensing signal amplitude. Neither clinical events nor patient complaints were reported. Significant imaging artefacts were present on 11 of 39 scans (28.2%). These artefacts were significantly more frequent in ICDs (8 of 8, 100%) vs. PMs (3 of 31, 9.7%) (P < 0.001). Diagnostic questions were answered in 92.3% of the cases, with just three pronounced artefacts preventing an adequate diagnosis in three ICD patients. CONCLUSIONS: Our results suggest that cardiac MRI may be performed safely in appropriately selected patients with close monitoring during the scan without limitation of peak SAR level using several precautionary measures. Image artefacts were more frequent in ICD patients.

Bone Deleterious Effects of Different NRTIs in Treatment-naïve HIV Patients After 12 and 48 Weeks of Treatment.

BACKGROUND: Bone alterations have been observed in the course of HIV infection, characterized by a marked decrease in bone mineral density (BMD) and an increase in the frequency of fractures as a result of fragility. We aim to evaluate early changes in bone metabolic profile and the possible association with tenofovir and other nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs) in treatment-naïve HIV patients. METHODS: We conducted a prospective study in naïve HIV-infected adults (under 50 years), separated into three groups according to NRTI therapy: tenofovir disoproxil fumarate (TDF); tenofovir alafenamide (TAF) and abacavir (ABC). BMD and epidemiological, immunological and metabolic bone parameters were evaluated. Bone markers were analyzed in plasma at baseline, 12 and 48 weeks after initiating treatment. RESULTS: Average age of patients was 34.8 years (± 9.6). 92.4% of them with CD4 count > 200 cel/µL. At week 12 after starting treatment, both TDF [increase in PN1P (31.7%, p = 0.004), TRAP (11.1%, p = 0.003), OPN (19.3%, p = 0.045) and OC (38.6%, p = 0.001); decrease in OPG (-23.4%, p = 0.003)] and TAF [increase in 42.6% for CTX (p = 0.011), 27.3% for OC (p = 0.001) and 21% for TRAP (p = 0.008); decrease in OPG (-28.8%, p = 0.049)] presented a deep resorption profile compared to ABC, these differences in bone molecular markers, a tendency to equalize at week 48, where no significant differences were observed. Patients treated with TDF showed the greatest decrease in Z-score in both lumbar spine (LS) and femoral neck (FN) at week 48 without statistically significant differences. CONCLUSION: Treatment-naïve HIV patients have a high prevalence of low bone density. Treatment with TDF is associated with greater bone deterioration at 12 and 48 weeks. TAF seems to present similar early bone deterioration at 12 weeks which disappears at 48 weeks.

ß2-Adrenoceptors and GRK2 as Potential Biomarkers in Patients With Chronic Pulmonary Regurgitation.

Pulmonary regurgitation (PR) is a frequent complication after repair of congenital heart disease. Three different GRK isoforms (GRK2, GRK5, and GRK3) and two ß-adrenoceptors (ß1-AR and ß2-AR) are present in peripheral blood mononuclear cells (PBMC) and their expression changes as a consequence of the hemodynamic and neurohumoral alterations that occur in some cardiovascular diseases. Therefore, they could be useful as biomarkers in PR. A prospective study was conducted to describe the expression (TaqMan Gene Expression Assays) of ß-ARs and GRKs in PBMC isolated (Ficoll® gradient) from patients with severe PR before and after pulmonary valve replacement and establish if this expression correlates to clinical status. 23 patients with severe PR were included and compared with 22 healthy volunteers (controls). PR patients before the PVR had a significantly lower expression of ß2-AR (513.8 ± 261.2 mRNA copies) vs. controls (812.5 ± 497.2 mRNA copies), so as GRK2 expression (503.4 ± 364.9 copies vs. 858.1 ± 380.3 mRNA copies). The expression of ß2-AR and GRK2 significantly decreases in symptomatic and asymptomatic patients, as well as in patients under treatment with beta-blockers and non-treated patients. The expression of ß2-AR and GRK2 in PR patients recovers the normal values after pulmonary valve replacement (754,8 ± 77,1 and 897,8 ± 87,4 copies, respectively). Therefore, changes in the expression of ß2-AR and GRK2 in PBMC of PR patients, could be considered as potential biomarkers to determine clinical decisions.

Tenofovir Causes Bone Loss via Decreased Bone Formation and Increased Bone Resorption, Which Can Be Counteracted by Dipyridamole in Mice.

Osteopenia and fragility fractures have been associated with human immunodeficiency virus (HIV) infection. Tenofovir, a common antiviral in HIV treatment, also leads to increases in bone catabolism markers and decreased BMD in children and young adults. In murine models and human cell lines, tenofovir inhibits adenosine triphosphate release and decreases extracellular adenosine levels. Adenosine and adenosine A2A receptor inhibit osteoclast formation, and increase local adenosine concentration with dipyridamole, an agent that blocks adenosine cellular uptake and stimulates new bone formation as well as bone morphogenic protein 2. We hypothesized that tenofovir regulates bone resorption by diminishing endogenous adenosine levels and questioned whether dipyridamole may be a useful treatment to counteract the deleterous bone effects of tenofovir. Primary murine osteoclasts were induced by M-CSF/RANKL, and the number of TRAP-positive-cells was studied after challenge with tenofovir alone or in combination with dipyridamole. Differentiation markers were studied by RT-PCR and MAPK/NFkB expression by Western blot. Male C57Bl/6 mice were treated as follows: saline 0.9% (control), tenofovir 75 mg/kg/day, dipyridamole 25 mg/kg/day, combination tenofovir/dipyridamole (n = 10, 4 weeks). Calcein/Alizarin Red-labeling of newly formed bone was used, and long bones were prepared for micro-computed tomography (µCT)/histology. Tenofovir produced a dose-dependent increase in osteoclast differentiation (EC50 = 44.5nM) that was reversed by dipyridamole (IC50 = 0.3 µM). Tenofovir increased cathepsin K and NFATc1 mRNA levels and dipyridamole reversed the effect. Dipyridamole reversed the effect of tenofovir on pERK1/2, pp38, and NFkB nuclear translocation. Mice treated with tenofovir lost nearly 10% of their body weight (p < 0.001). µCT revealed decreased BMD and altered trabecular bone in tenofovir-treated mice, reversed by dipyridamole. TRAP-staining showed increased osteoclasts in tenofovir-treated mice (p < 0.005), an effect reversed by dipyridamole. Similar results were obtained for cathepsin K and CD68. RANKL-positive cells were increased in tenofovir-treated mice, whereas osteoprotegerin-positive cells were decreased; both effects were reversed by dipyridamole. These results suggest that treatment with agents that increase local adenosine concentrations, like dipyridamole, might prevent bone loss following tenofovir treatment. © 2019 American Society for Bone and Mineral Research.

Value of the Electrocardiogram as a Predictor of Right Ventricular Dysfunction in Patients With Chronic Right Ventricular Volume Overload.

INTRODUCTION AND OBJECTIVES: Pulmonary regurgitation is a common complication in patients with repaired tetralogy of Fallot or congenital pulmonary stenosis. Electrocardiographic variables have been correlated with parameters used to evaluate right ventricular function. We aimed to analyze the diagnostic value of the width and fragmentation of the electrocardiogram in the identification of patients with right ventricular dysfunction and/or dilation. METHODS: We selected 107 consecutive patients diagnosed with severe pulmonary insufficiency after repair of pulmonary stenosis or tetralogy of Fallot. The tests included electrocardiography, echocardiography, and magnetic resonance. Each electrocardiogram was analyzed manually to measure QRS duration. We defined QRS fragmentation as the presence of low-voltage waves in the terminal portion of the QRS complex in at least 2 contiguous leads. RESULTS: We found a significant negative correlation between QRS width and right ventricular function, as well as a positive correlation with right ventricular volume. The receiver operating characteristic curve indicated a cut-off point for QRS width of 140ms, which showed good sensitivity for a diagnosis of right ventricular dilation (> 80%) and dysfunction (> 95%). In logistic regression models, a QRS duration > 140ms was found to be the only independent predictor of right ventricular dilation and dysfunction. CONCLUSIONS: Electrocardiography is a rapid, widely available, and reproducible tool. QRS width constitutes an independent predictor of the presence of right ventricular dilation and dysfunction. This study is the first to provide a cutoff value for QRS width to screen for right ventricle involvement.

Myocardial and lymphocytic expression of eNOS and nNOS before and after heart transplantation: relationship to clinical status.

AIMS: The present study investigates the expression and clinical relevance of the constitutive NO synthases in heart and peripheral blood mononuclear cells (PBMCs) obtained from heart failure patients. MAIN METHODS: mRNA and protein levels (qRT-PCR and immunoblot) of eNOS and nNOS were determined in: i) Left ventricle (LV, n=4) and PBMCs (n=10) from healthy donors; ii) LV, right ventricle (RV) and PBMCs of heart failure (HF) patients (n=32); and iii) biopsies and PBMCs of the HF patients after cardiac transplant (n=15). KEY FINDINGS: Expression of constitutive NOS isoforms in heart exhibits wide variability in HF patients, but this variability was not related to aetiology, disease severity, concomitant pathologies or drug regimes. A significantly increased eNOS expression was found in LV from HF patients without vs. with pulmonary hypertension. Overall, higher eNOS expression in this chamber was associated with lower pulmonary arterial pressure. Furthermore, a higher eNOS expression in HF is associated with smaller LV diameter, whereas, a higher post-transplant eNOS expression is related to greater cardiac distensibility. In the RV, nNOS increased after transplant. The positive correlation found between the nNOS expression in the LV of HF patients and the cardiac index suggests a role for this isoform in facilitating cardiac work. A decreased expression of eNOS was observed in PBMCs from HF patients vs. healthy donors, which recovers after transplant. SIGNIFICANCE: A selective up-regulation of the cardiac expression of each NOS isoform in the failing heart, which is not mirrored by PBMCs, is related to an improved health status.

Influence of metabolic syndrome on development of cardiac allograft vasculopathy in the transplanted heart.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is the main cause of graft failure and death 1 year after heart transplantation (HTx). Metabolic syndrome (MS) increases the risk of cardiovascular events by endothelial dysfunction. The purpose of this study was to determine if patients with MS developed a higher risk of CAV 1 year after HTx. METHODS: Since January 2004 until April 2009, 155 HTx patients were recruited. Cardiopulmonary transplants were excluded (12 patients), as well as retransplants (5 patients), pediatric transplants (11 patients), patients who refused to participate (3 patients), and those who died during the first year (35 patients). The final analysis included 89 patients. MS was diagnosed when Adult Treatment Panel III modified and revised criteria were met, before HTx or after the first 3 months. CAV was diagnosed through intravascular ultrasound performed 1 month and 1 year after HTx. CAV was defined as an intimal thickening ≥ 0.5 mm in the follow-up with regard to the one of the basal study. RESULTS: Development of CAV was significantly higher in patients with MS (59% vs. 19%, P<0.0001). Patients with more criteria of MS had a higher development of CAV: no criteria (4%); one criterion (4%); two criteria (47%); three criteria (62%); four criteria (75%); and five criteria (100%). Variables related to CAV in a multivariate analysis were MS (odds ratio [OR] 7.97; 95% confidence interval [CI]: 2.77-22.96; P<0.001), donor's age (OR 1.07; 95% CI: 1.01-1.13; P=0.019), low high-density lipoprotein cholesterol (OR 0.26; 95% CI: 0.09-0.71; P=0.009), and hypertriglyceridemia (OR 4.08; 95% CI: 1.45-11.50; P=0.008). CONCLUSIONS: Presence of MS distinguishes a subgroup of patients with high risk of developing CAV. Narrow and personalized monitoring of these patients would be recommendable.