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Several lines of evidence suggest that binding SARS-CoV-2 antibodies such as anti-SARSCoV-2 RBD IgG (anti-RBD) and neutralising antibodies (NA) are correlates of protection against SARS-CoV-2, and the correlation of anti-RBD and NA is very high. The effectiveness (VE) of BNT162b2 in preventing SARS-CoV-2 infection wanes over time, and this reduction is mainly associated with waning immunity, suggesting that the kinetics of antibodies reduction might be of interest to predict VE. In a study of 97 health care workers (HCWs) vaccinated with the BNT162b2 vaccine, we assessed the kinetics of anti-RBD 30–250 days after vaccination using 388 individually matched plasma samples. Anti-RBD levels declined by 85%, 92%, and 95% at the 4th, 6th, and 8th month from the peak, respectively. The kinetics were estimated using the trajectories of anti-RBD by various models. The restricted cubic splines model had a better fit to the observed data. The trajectories of anti-RBD declines were statistically significantly lower for risk factors of severe COVID-19 and the absence of vaccination side effects. Moreover, previous SARS-CoV-2 infection was associated with divergent trajectories consistent with a slower anti-RBD decline over time. These results suggest that anti-RBD may serve as a harbinger for vaccine effectiveness (VE), and it should be explored as a predictor of breakthrough infections and VE. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Due to their higher risk of developing life-threatening COVID-19 disease, solid organ transplant (SOT) recipients have been prioritized in the vaccination programs of many countries. However, there is increasing evidence of reduced immunogenicity to SARS-CoV-2 vaccination. The present study investigated humoral response, safety, and effectiveness after the two mRNA vaccines in 455 SOT recipients. Overall, the antibody response rate was low, at 39.6%. Higher immunogenic-ity was detected among individuals vaccinated with the mRNA1273 compared to those with the BNT162b2 vaccine (47% vs. 36%, respectively, p = 0.025) as well as higher median antibody levels of 31 (7, 372) (AU/mL) vs. 11 (7, 215) AU/mL, respectively. Among the covariates assessed, vaccination with the BNT162b2 vaccine, antimetabolite-and steroid-containing immunosuppression, female gender, the type of transplanted organ and older age were factors that negatively influenced immune response. Only mild adverse effects were observed. Our findings confirm poor immunogenicity after vaccination, implicating a reevaluation of vaccination policy in SOT recipients. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Due to their higher risk of developing life-threatening COVID-19 disease, solid organ transplant (SOT) recipients have been prioritized in the vaccination programs of many countries. However, there is increasing evidence of reduced immunogenicity to SARS-CοV-2 vaccination. The present study investigated humoral response, safety, and effectiveness after the two mRNA vaccines in 455 SOT recipients. Overall, the antibody response rate was low, at 39.6%. Higher immunogenicity was detected among individuals vaccinated with the mRNA1273 compared to those with the BNT162b2 vaccine (47% vs. 36%, respectively, p = 0.025) as well as higher median antibody levels of 31 (7, 372) (AU/mL) vs. 11 (7, 215) AU/mL, respectively. Among the covariates assessed, vaccination with the BNT162b2 vaccine, antimetabolite- and steroid-containing immunosuppression, female gender, the type of transplanted organ and older age were factors that negatively influenced immune response. Only mild adverse effects were observed. Our findings confirm poor immunogenicity after vaccination, implicating a reevaluation of vaccination policy in SOT recipients.

The mRNA vaccine BNT162b2 has proven highly effective and currently many millions are being vaccinated. There are limited and conflicting data from immunogenicity studies on the effects of age, gender, vaccination side effects (VSE), risk factors for severe COVID-19 (RFS-COV), obesity (BMI) and previous SARS-CoV-2 (Pr-CoV) Moreover, immunogenicity data from COVID-19 patients comparing various disease categories of natural infection i.e. asymptomatic vs mild vs moderate vs severe infection are sparse, and include limited number of individuals.This study included 871 vaccinated health care workers (HCW) and 181 patients with natural infection. Immunogenicity was assessed by a quantative assay measuring anti-SARS-CoV-2 against the RBD domain of the spike protein (anti-RBD) and anti-SARS-CoV-2 against nucleocapsid protein (anti-N). Samples were collected 1-2 weeks after completion of the 2nd dose in the vaccinated HCWs and 15-59 days post symptoms onset in patients with natural infection.The concentration of anti-RBD in vaccinated individuals after multivariable analysis was significantly associated with age, gender, VSE and Pr-CoV. Specifically, anti-RBD median levels (95% CI) were lower by 2,466 (651-5,583), 6,228 (3,254-9,203) and 7,651 (4,479-10,823) AU/ml in 35-44, 45-54, 55-70 yrs respectively, compared with 18-34 yrs group. In females, median levels of anti-RBD were higher by 2,823 (859-4,787) compared with males, in individuals with VSE were higher by 5,024 (3,122-6,926) compared with no VSE, and in HCWs with Pr-CoV were higher by 9,971 (5,158-14,783) AU/ml compared with HCWs without Pr-CoV.Among individuals with natural infection, the median anti-RBD levels were 14.8 times higher in patients with critical COVID-19 infection compared with non-hospitalized individuals. The ratio of anti-RBD in vaccinated individuals versus those with natural infection varied from 1.0 up to 19.4 according to the clinical subgroup of natural infection.This study proves the high immunogenicity of BNT162b2 vaccine although its sustainability remains to be seen. The use of comparative data from natural infection serological panels, expressing the clinical heterogeneity of natural infection may facilitate early decisions for vaccine evaluation in clinical trials.

Vitamin-K antagonists (VKAs) have remained the mainstay of oral anticoagulant therapy for the treatment and prevention of thromboembolism. The management of treatment with VKAs is challenging due to their narrow therapeutic index and the wide interindividual variation in response to therapy. Variants of the CYP2C9 and the VKORC1 gene account for 30–50% of the variability in dosing requirements, and it has been proposed that genotyping of these loci could facilitate management of VKA therapy and minimize risk of overanticoagulation, even in very low doses. We present the first reported case of a patient with the compounded genotype CYP2C9*3*3 and VKORC1-1639A/A under treatment with acenocoumarol, and review of other reported cases with analogous genotypic profiles but under treatment with warfarin.

BNT162b2 has proven to be highly effective, but there is a paucity of data regarding immunogenicity factors and comparison between response to vaccination and natural infection. This study included 871 vaccinated healthcare workers (HCW) and 181 patients with natural infection. Immunogenicity was assessed by measuring anti-SARS-CoV-2 against the RBD domain of the spike protein (anti-RBD). Samples were collected 1–2 weeks after vaccination or 15–59 days post-onset of symptoms. Post-vaccine anti-RBD concentrations were associated with age, gender, vaccination side-effects (VSE) and prior infection (Pr-CoV). Anti-RBD median levels (95%CI) were lower by 2466 (651–5583), 6228 (3254–9203) and 7651 (4479–10,823) AU/mL in 35–44, 45–54, 55–70 yrs, respectively, compared with the 18–34 yrs group. In females, the median levels were higher by 2823 (859–4787), 5024 (3122–6926) in individuals with VSE, and 9971 (5158–14,783) AU/mL in HCWs with Pr-CoV. The ratio of anti-RBD in vaccinated individuals versus those with natural infection varied from 1.0 to 19.4. The high immunogenicity of BNT162b2 is verified, although its sustainability has yet to be elucidated. The use of comparative data from natural infection serological panels, expressing the clinical heterogeneity of natural infection, may facilitate early decisions for candidate vaccines to be evaluated in clinical trials. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Ventricular assist devices (VADs) have been associated with the development of anti-HLA antibodies ('allosensitization'), but data on devices providing biventricular support in adults are limited. We sought to characterize differences in anti-HLA antibody formation in adult patients receiving left- (LVAD) versus biventricular- (BiVAD) assist devices as bridge to transplantation (BTT) by retrospectively reviewing the records of adult patients who have undergone VAD implantation at our institution. We assessed 82 patients supported with a pulsatile-flow paracorporeal BiVAD and compared them with 40 patients receiving LVAD till 2018. Forty-eight (58.5%) of the BiVAD and 23 (57.5%) of the LVAD patients were eventually transplanted (p = 0.91) with an average time to transplantation 559 and 598 days, respectively (p = 0.73). Evidence of sensitization pre-VAD was found in 11.0% of the BiVAD patients and 15.0% of the LVAD ones (p = 0.53); these percentages rose to 43.9% (p 0.001) and 40.0% (p = 0.01), respectively. The post-VAD sensitization status was not significantly different between the BiVAD and the LVAD group (p = 0.68). De novo sensitization was comparable between the two groups (p = 0.55). Post-transplantation outcomes regarding rejections and cardiac allograft vasculopathy were also similar. Conclusively, BiVAD- and LVAD- induced allosensitization do not appear to differ significantly.

BNT162b2 has proven to be highly effective, but there is a paucity of data regarding immunogenicity factors and comparison between response to vaccination and natural infection. This study included 871 vaccinated healthcare workers (HCW) and 181 patients with natural infection. Immunogenicity was assessed by measuring anti-SARS-CoV-2 against the RBD domain of the spike protein (anti-RBD). Samples were collected 1–2 weeks after vaccination or 15–59 days post-onset of symptoms. Post-vaccine anti-RBD concentrations were associated with age, gender, vaccination side-effects (VSE) and prior infection (Pr-CoV). Anti-RBD median levels (95%CI) were lower by 2466 (651–5583), 6228 (3254–9203) and 7651 (4479–10,823) AU/mL in 35–44, 45–54, 55–70 yrs, respectively, compared with the 18–34 yrs group. In females, the median levels were higher by 2823 (859–4787), 5024 (3122–6926) in individuals with VSE, and 9971 (5158–14,783) AU/mL in HCWs with Pr-CoV. The ratio of anti-RBD in vaccinated individuals versus those with natural infection varied from 1.0 to 19.4. The high immunogenicity of BNT162b2 is verified, although its sustainability has yet to be elucidated. The use of comparative data from natural infection serological panels, expressing the clinical heterogeneity of natural infection, may facilitate early decisions for candidate vaccines to be evaluated in clinical trials.

Background Presence of anti-Human Leukocyte Antigen (anti-HLA) alloantibodies (allosensitization) in a heart transplantation candidate impedes the chance of finding a compatible transplant. Left Ventricular Assist Devices (LVADs) have been shown to induce allosensitization. Purpose The purpose of this study is to characterize anti-HLA allosensitization in adult patients receiving left (LVAD) versus biventricular- (BiVAD) assist devices as bridge to transplantation (BTT). Methods This study retrospectively assessed anti-HLA antibody induction in all adult patients who have received either LVAD or BiVAD as BTT at our institution. Anti-HLA alloantibody screening was performed before, and at multiple time-points after VAD implantation. Anti-HLA antibody detection was performed with a cytotoxic panel-reactive antibody (PRA) method until 2003, enzyme-linked immunoassay (ELISA) method from 2003 to 2005 and SAB assays on the Luminex platform from 2005 to 2017. Sensitization was defined either as PRA >10%, or as peak anti-HLA antibody mean fluorescence intensity (MFI) values of more than 1000. Baseline characteristics and sensitization in the two patient groups were evaluated using descriptive statistics. Results Between 2003 and 2018, 154 patients were placed on VAD support at our institution as BTT. Sensitization data were available for 130 patients. Fifty five (36.6%) patients were supported with an LVAD (median age, 48 years, 26% female) and 95 (63.4%) with a BiVAD (median age, 45 years, 28% female). Twenty-five (45.4%) of the LVAD and 49 (51.2%) of the BiVAD patients were eventually transplanted (p=0.47) with an average time to transplantation 588 and 562 days respectively. Fifteen (27.2%) LVAD and 35 (36.8%) BiVAD patients died before transplantation (p=0.23) with an average time on VAD support before death 269 and 302 days respectively. Evidence of sensitization pre-VAD was found in 17.1% of the LVAD and 12.5% of the BiVAD patients (p=0.53); these percentages rose to 40.0% (p=0.001) and 43.7% (p=0.0001) respectively at 2 to 12 months post-VAD implantation. However, the post-VAD allosensitization status was not statistically different between the LVAD and the BiVAD group. Among the 25 LVAD patients who were transplanted 7 (30.4%) were sensitized immediately before transplantation, compared to 22 (46.8%) out of 49 BiVAD patients (p=0.16). Conclusion Both LVADs and BiVADs are a factor of de novo anti-HLA antibody development in adult patients after implantation. Sensitization pattern does not seem to differ between LVAD and BiVAD patients. Additionally, patients supported by LVAD or BiVAD have similar chances of finding a suitable donor heart.

Vitamin-K antagonists (VKAs) have remained the mainstay of oral anticoagulant therapy for the treatment and prevention of thromboembolism. The management of treatment with VKAs is challenging due to their narrow therapeutic index and the wide interindividual variation in response to therapy. Variants of the

Cardiac surgery is associated with inflammation and oxidative stress; malondialdehyde (MDA) is a marker of oxidative stress and osteopontin (OPN) is a proinflammatory cytokine. We studied MDA kinetics following coronary artery bypass grafting (CABG) and its relation to OPN. We evaluated 50 consecutive patients (60 ± 10 year-old, 44 men and 6 women) with stable coronary artery disease and left ventricular ejection fraction of 50 ± 8 % undergoing elective CABG on pump. Peripheral plasma samples were drawn at baseline, 24 and 72 h postoperatively. OPN was evaluated at baseline and MDA and cardiac enzymes at all time points. MDA levels increased significantly at 72 h postoperative compared with preoperative and 24 h postoperative levels whereas there was no difference between the pre and first postoperative values (p = 0.67). MDA change was positively correlated with the change in troponin at baseline and at 72 h (r = 0.6, p = 0.022) as well as with preoperative OPN levels (r = 0.28, p = 0.047). There was a significant positive correlation between MDA at 72 h and age (r = 0.27, p = 0.039). In addition, MDA change differed significantly in relation to diabetes at baseline and at 72 h—2.99 (4.77) in diabetics versus 0.69 (3.82) in non-diabetics (p = 0.05). MDA increases post on-pump CABG but only at 72 h and this increase correlates with preoperative OPN levels. In addition, MDA increase is related to age and diabetes as well as troponin increase following surgery.

Bloodstream infections (BSIs) constitute a frequent post-transplant complication in thoracic allograft recipients, especially during the early post-surgical period when patients are under intense immunosuppression. Thus, early and accurate identification of the responsible pathogens is of critical importance for patient survival. In this study we investigated the potential clinical utility of a multiplex real-time polymerase chain reaction (PCR) technology (SeptiFast; Roche Diagnostics) for the detection of BSIs in a cohort of thoracic allograft recipients.Our observational study included analysis of 130 blood samples from 30 thoracic allograft recipients (23 heart and 7 lung) using SeptiFast in parallel with blood culture. Samples were drawn when there were clinical and laboratory signs of BSI. The applied molecular assay has been designed to allow direct detection of a wide panel of Gram-positive and Gram-negative bacteria and fungi in blood samples.Real-time PCR yielded concurrent negative and positive results with blood culture methodology in 113 (86.9%) and 5 (3.9%) samples, respectively, with 100% concordance in species identification. SeptiFast identified microorganisms in 9 (6.9%) additional samples that were negative by blood culture. The combined use of SeptiFast and blood culture during the early post-transplant period (2 months) significantly increased the number of positive samples detected to 17.9% (14 of 78) from 7.7% (6 of 78) detected by blood culture alone (p0.05). SeptiFast results were available, on average, within 6 hours from sample collection.The PCR-based SeptiFast test is a valuable addition to the traditional blood culture method for rapid etiologic diagnosis of BSIs in thoracic transplant recipients, especially during the early post-transplant period.

Introduction Recently new human leukocyte antigen (HLA) antibody screening methods have been shown to significantly improve thoracic transplantation outcomes. The best combination of assays for both allocation and monitoring is still under investigation. Herein, we evaluated the correlation and clinical relevance of three methodologies to detect donor-specific anti-HLA antibodies (DSA). Methods For the same donor-recipient combinations we compared the results of the Luminex donor-specific crossmatch (DSA-LX), using donor-isolated HLA antigens coated onto microbeads, with those of a flow-cytometric crossmatch (FCXM) and of the Luminex single-antigen bead methodology (SA-LX), wherein recombinant HLA molecules are coated onto microbeads. We compared 46 pre- (n = 27) and post-transplant (n = 19) serum samples using DSA-LX and SA-LX, while 27 pretransplant samples were additionally analyzed by FCXM. Results Among the pretransplant sera, the 3 methods were in agreement for class I DSA in 22/27 (81.5%) samples and for class II DSA in 17/27 (63.0%) of tested samples. When the results of the 2 bead-based methodologies were compared with the FCXM methodology, the SA-LX results better correlated than the DSA-LX results both for class I and class II antibodies. Furthermore, the SA-LX results showed greater clinical relevance. The reproducibility scores for both the SA-LX and FCXM were 100%, whereas for the DSA-LX it was 85.5%. Conclusions DSA-LX did not correlate with FCXM and SA-LX to detect DSA, particularly for class II antibodies. Furthermore, in comparison to FCXM and SA-LX, DSA-LX showed lower reproducibility rendering the method not eligible for prediction, allocation, or monitoring purposes.

Cardiovascular events may occur even after complete revascularization in patients with coronary artery disease. We measured preoperative osteopontin (OPN) levels in 131 consecutive patients (66.5±10years old, 117 men and 14 women) with left ventricular ejection fraction of50.7±9.2%and low logistic EuroScore (3.5±3.2%) undergoing elective Coronary Artery Bypass Grafting (CABG) surgery. Patients were prospectively followed up for a median of 12 months (range 11–24). The primary study endpoint was the composite of cardiovascular death, nonfatal myocardial infarction, need for repeat revascularization, and hospitalization for cardiovascular events. Pre-op OPN plasma levels were 77.9 (49.5, 150.9). Patients with prior acute myocardial infarction (AMI) had significantly higher OPN levels compared to those without [131.5 (52.2, 219) versus 73.3 (45.1, 125),p=0.007]. OPN levels were positively related to EuroScore (r=0.2,p=0.031). Pre-op OPN levels did not differ between patients who had a major adverse event during follow-up compared to those with no event (p=0.209) and had no effect on the hazard of future adverse cardiac events [HR (95% CI): 1.48 (0.43–4.99),p=0.527]. The history of AMI was associated with increased risk of subsequent cardiovascular events at follow-up (p=0.02). OPN is associated with preoperative risk assessment prior to low-risk CABG but did not independently predict outcome.

Background: Inflammatory mechanisms are key to the pathogenesis of atherosclerosis. Functional polymorphisms of TLR-4, Asp299Gly and Thr399Ile, CD14 promoter area C260T polymorphism and plasma levels of soluble CD14 are studied in subjects with Coronary Artery Disease (CAD). Methods: DNA was obtained from 100 human paraffin-embedded aortic specimens, from cadavers with known coronary atheromatosis (Group A) and 100 blood samples from patients with CAD, as detected by cardiac Multi-Detector-row-Computed-Tomography (MDCT) (Group B). Our control group consisted of 100 healthy individuals (Group C). Genotyping was performed by Restriction Fragment Length Polymorphism-Polymerase Chain Reaction (RFLP-PCR). Plasma levels of sCD14 were measured with ELISA. Results: For TLR-4 Asp299Gly and Thr399Ile polymorphisms, no statistically significant differences were observed. Regarding the C260T polymorphism, frequencies of T allele were significantly higher in the control group compared to the case group (p = 0.05). The Odds Ratio (OR) showed statistically significant association of TT genotype with healthy individuals (OR 0.25, 95% Confidence Interval CI 0.10–0.62, p = 0.0017). Plasma levels of sCD14 in patients with CAD (mean value = 1.35 μg/mL) were reduced when compared to reference value. Conclusions: The studied polymorphisms ofTLR-4 showed no association with CAD. Conversely, the functional polymorphism of CD14 has a statistically significant difference in expression between healthy and affected by CAD individuals.

Cardiovascular events may occur even after complete revascularization in patients with coronary artery disease. We measured preoperative osteopontin (OPN) levels in 131 consecutive patients (66.5 ± 10 years old, 117 men and 14 women) with left ventricular ejection fraction of 50.7 ± 9.2 % and low logistic EuroScore (3.5 ± 3.2 %) undergoing elective Coronary Artery Bypass Grafting (CABG) surgery. Patients were prospectively followed up for a median of 12 months (range 11-24). The primary study endpoint was the composite of cardiovascular death, nonfatal myocardial infarction, need for repeat revascularization, and hospitalization for cardiovascular events. Pre-op OPN plasma levels were 77.9 (49.5, 150.9). Patients with prior acute myocardial infarction (AMI) had significantly higher OPN levels compared to those without [131.5 (52.2, 219) versus 73.3 (45.1, 125), p = 0.007 ]. OPN levels were positively related to EuroScore (r = 0.2, p = 0.031). Pre-op OPN levels did not differ between patients who had a major adverse event during follow-up compared to those with no event (p = 0.209) and had no effect on the hazard of future adverse cardiac events [HR (95% CI): 1.48 (0.43-4.99), p = 0.527 ]. The history of AMI was associated with increased risk of subsequent cardiovascular events at follow-up (p = 0.02). OPN is associated with preoperative risk assessment prior to low-risk CABG but did not independently predict outcome. © 2016 Eftihia Sbarouni et al.

Aims To identify potential genetic associations of five cytokine gene polymorphisms with disease severity and prognosis in patients with idiopathic dilated cardiomyopathy (DCM). Methods and results Eighty patients with DCM were genotyped for transforming growth factor beta1 (TGF-β1) +869 T/C (codon10 Leu → Pro), TGF-β1 +915 G/C (codon25 Arg → Pro), interleukin (IL)-6 −174G/C, tumor necrosis factor-alpha (TNF-α) −308A/G, interferon-gamma (IFN-γ) +874T/A, IL-10 −1082A/G, IL-10 −819T/C and IL-10 −592A/C gene polymorphisms. In homozygous TT patients for TGF-β1 +869 T/C polymorphism mean VO 2 max was significantly higher than in CC homozygous patients (25.67 ± 6.73 ml/kg/min vs. 20.29 ± 6.35 ml/kg/min, p = 0.046), which remained significant only for patients younger than 39 years old after adjusting for age and sex ( p = 0.009). C carriers of TGF-β1 +915 G/C polymorphism are 4.2 times more likely to be in a worse NYHA stage (III–IV) than non C carriers [OR: 4.25, 95% CI (1.53–11.80), p = 0.006]. Patients GG homozygous for IL-6 −174G/C polymorphism presented greater left ventricle end-systolic ( p = 0.018) and end-diastolic ( p = 0.04) diameters in comparison to the CC homozygous. The AA homozygote for IFN-γ +874T/A polymorphism ( p = 0.02) and the combination of the TGF-β1 +869 T/C and TGF-β1 +915 G/C genotypes were associated with adverse outcome ( p = 0.014). Conclusion Specific cytokine gene polymorphisms seem to be associated with worse prognosis as well as with measures of disease severity in DCM.

Heart-type fatty acid-binding protein (H-FABP) is considered a marker of myocardial necrosis but whether or not it is modified by myocardial ischemia is not clear. We sought to investigate if H-FABP serum levels increase following non-urgent coronary angioplasty.We studied 31 patients undergoing coronary angioplasty. Peripheral venous samples were drawn immediately before angioplasty, 1 h after the first balloon inflation and 24 h after the procedure and assayed for H-FABP.Serum levels of H-FABP increased significantly at 1 h vs baseline from 2554 +/- 1268 to 3322 +/- 245 pg ml(-1) (p = 0.024). However, no differences were observed between 1 h and 24 h after angioplasty (3268 +/- 1861 vs 3322 +/- 2459 pg ml(-1), p = 0.87). Moreover, no significant difference was observed when we compared 24 h after angioplasty with the baseline (3268 +/- 1861 vs 2554 +/- 1268 pg ml(-1), p = 0.112).We conclude that H-FABP significantly increases after elective coronary angioplasty at 1 h compared with baseline values; whether or not this has any prognostic significance for future events, as it occurs with troponins, needs to be studied further.

Abundant evidence supports the central role of inflammatory cytokines in immune responses mediating the pathogenesis of atherosclerosis, coronary artery disease, and its complications, such as myocardial infarction and unstable angina.We investigated the association of genetic polymorphisms of the inflammatory cytokines, IL-10, TGF-beta1, IFN-gamma, IL-6, and TNF-alpha with the clinical presentation of coronary artery disease in 26 patients with stable angina, 45 patients with unstable angina and 58 patients who had experienced nonfatal myocardial infarction. Genotyping was performed by the sequence-specific primer polymerase chain reaction method.A significant difference in the frequencies of -174G/C IL-6 alleles was observed, with the low in-vitro producing -174*C allele predominating in patients with myocardial infarction, compared with stable angina and unstable angina patients, after the analysis of genotypes (P=0.024 and 0.022, respectively), phenotypes [P=0.0099, odds ratio (OR)=0.271, 95% confidence interval (CI)=0.1012-0.7292; P=0.03, OR=0.40, respectively] and haplotypes (P=0.007, OR=3.028, 95% CI=1.347-6.806; P=0.0096, OR=2.368, 95% CI=1.262-4.444; respectively). In addition, a predominance of the -1082ACC/ATA IL-10 genotype in the myocardial infarction group compared with the unstable angina group and the -874 A/A IFN-gamma genotype in the stable angina group compared with the unstable angina and the myocardial infarction group, was found. No significant differences in the distribution of genotypes, phenotypes and haplotypes in the three study groups, for the TNF-alpha-308 A/G and TGF-beta1-codon 25 G/C, codon 10 T/C polymorphisms were detected.Our data provide evidence that the IL-6-174G/C polymorphism may be involved in the pathogenesis of coronary artery disease, contributing to genetic susceptibility for myocardial infarction.

Purpose To assess the effects of inspiratory muscle training (IMT) on autonomic activity, endothelial function, and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with chronic heart failure. Methods Using age- and sex-matched controlled study, 23 patients (mean left ventricular ejection fraction 29 +/- 2%) were assigned to either a high-intensity training group (n = 14), New York Heart Association (NYHA) class II (n = 9)/III (n = 5), or a low-intensity training group (n = 9), NYHA class II (n = 6)/III (n = 3), exercising at 60% and 15% of sustained maximum inspiratory pressure (SPImax), respectively, 3 times per week for 10 weeks. Before and following IMT, patients underwent cardiopulmonary exercise testing and dyspnea evaluation on exertion. Sympathovagal balance was assessed by heart rate variability (HRV) from 24-hour electrocardiogram and endothelial function, using venous occlusion plethysmography. Serum levels of NT-proBNP were determined. Results High-intensity training group improved maximum inspiratory pressure (PImax, 105.4 +/- 5.3 vs 79.1 +/- 5 cm H2O, P = .001), SPImax (511 +/- 42 vs 308 +/- 28 cm H2O/sec/10, P = .001), peak oxygen consumption (19 +/- 1.2 vs 17.1 +/- 0.7 mL.kgmin, P = .01) and dyspnea (17.6 +/- 0.2 vs 18.1 +/- 0.1, P = .02). Endothelium-dependent vasodilation, HRV, and NT-proBNP levels were not altered. Low-intensity training group increased only the PImax (97.6 +/- 11.3 vs 84.2 +/- 8.7 cm H2O, P = .03). Conclusions Improvement in dyspnea and exercise tolerance after IMT were not associated with changes in markers of HRV, endothelial function, and NT-proBNP in patients with mild to moderate chronic heart failure. Further studies on the effects of IMT in advanced heart failure would be worthwhile.

Background The effects of inspiratory muscle training on plasma cytokines, C-reactive protein and the soluble apoptosis mediators Fas and Fas ligand in chronic heart failure are unknown. Design and methods Thirty-eight patients with chronic heart failure, age 57 ± 2 years, New York Heart Association classification II-III, were assigned to either a high intensity training group ( n = 15, age 53±2 years) exercised at 60% of sustained maximal inspiratory pressure, or a low intensity training group ( n = 23, age 59 ± 2 years), exercised at 15% of sustained maximal inspiratory pressure, three times per week for 10 weeks. Patients in the high intensity training group and low intensity training group were matched for age, sex and New York Heart Association functional class. Plasma levels of tumor necrosis factor (TNF)-α, soluble TNF receptor I, interleukin-6, C-reactive protein, soluble apoptosis mediators Fas and Fas ligand were measured at baseline and at post-inspiratory muscle training. Pulmonary function was assessed by spirometry, exercise capacity by a cardiopulmonary exercise test and the 6 min walk test, whereas dyspnea by the Borg scale after the 6 min walk test. Results High intensity training group improved inspiratory muscle strength (105.1 ± 4.9 vs. 79.8 ± 4.7 cmH2O, P < 0.001), sustained maximal inspiratory pressure (504.5 ± 39.7 vs. 312.5 ± 26.5cmH2O/s/103, P2 (19.4 ± 1.2 vs. 17.3 ± 0.9 ml/kg per min, P2O, PConclusion A high intensity inspiratory muscle training program resulted in improvement in functional status of chronic heart failure patients compared with low intensity inspiratory muscle training. Improvement in exercise capacity was not associated with an anti-inflammatory effect, although a beneficial influence on soluble TNF receptor I was recorded. Possible reasons include inadequate level of muscle mass exercise and the low pretraining New York Heart Association class. Eur J Cardiovasc Prev Rehabil14:679-685 © 2007 The European Society of Cardiology

Background: Acute coronary syndromes (ACS) are characterized by activation of systemic and local inflammatory mediators. The interrelation between these soluble inflammatory markers and their association with markers of myocardial necrosis have not been extensively studied. Hypothesis: The study was undertaken to evaluate the association of the systemic levels of matrix metalloproteinase-9 (MMP-9) and the tissue inhibitor of metalloproteinase-1 (TIMP-1), with C-reactive protein (CRP), interleukin-6 (IL-6), and serum troponin-I in patients admitted with ACS. Methods: Analysis of serum concentrations of the above inflammatory markers was performed in 53 patients with unstable angina (UA) and in 15 with non-ST-segment elevation myocardial infarction (NSTEMI) within 48 h of admission, and 34 patients with stable coronary artery disease. Results: Compared with patients with stable angina, those with ACS had elevated admission levels of MMP-9 (p = 0.04), CRP (p< 0.001), and IL-6 (p = 0.001), but not TIMP-1 (p = 0.55). Compared with patients with UA, those with NSTEMI also had higher levels of IL-6 (p< 0.001), CRP (p = 0.002), and MMP-9 (p = 0.05). Conclusions: In patients with ACS, the admission levels of inflammatory mediators, including MMP-9, CRP, and IL-6 are significantly elevated, specifically in association with serum troponin I. Systemic and local markers of inflammatory activity may be directly associated with myocardial injury.