Helena Bedanova

Tobacco smoking and cytokine levels in human epicardial adipose tissue: Impact of smoking cessation

BACKGROUND & AIMS Epicardial adipose tissue (EAT) is a source of a number of cytokines which could act in the pathogenesis of coronary artery disease (CAD). The potential relationship between known cardiovascular risk factors, such as smoking, dyslipidaemia or diabetes mellitus and EAT humoral signalling, has not been fully elucidated. Therefore, we designed and conducted a cross-sectional study to determine whether selected cardiovascular risk factors are linked to levels of cytokines in epicardial and subcutaneous adipose tissue (SAT). METHODS Samples of SAT and EAT were collected from consecutive patients undergoing scheduled cardiac surgery. Tissue concentrations of tumour necrosis factor-ɑ (TNF-α), interleukin-6 (IL-6), adipocyte fatty acid-binding protein, leptin, and adiponectin were determined by ELISA. RESULTS We enrolled 140 patients. TNF-α and IL-6 concentrations in EAT and SAT were significantly higher in current smokers (CS) than in never smokers (NS) and former smokers (FS). There were no differences between FS and NS. No other clinical variables were associated with cytokine concentrations in a regression analysis. CONCLUSIONS Smoking was independently associated with higher TNF-α and IL-6 concentrations in EAT and SAT. A novel observation that pro-inflammatory cytokines are elevated in EAT in smokers could contribute to identify potential mechanisms involved in the pathogenesis of adverse effects of tobacco smoking. There were no differences between EAT cytokine production in NS and FS, which support the importance of smoking cessation for cardiovascular risk reduction.

Successful Re-Use of the Transplanted Heart

The case of re-use of a previously transplanted heart after brain death of the first recipient is reported. The second recipient was a 60-year-old man who suffered end-stage ischemic heart disease. The operative and postoperative course was uneventful, with the exception of secondary diabetes. The patient is post-transplantation by more than 10 months and is now in New York Heart Association functional class I. This case confirms the possibility of using this procedure, particularly in the situation when there is a shortage of organ donors.

High prevalence of exercise-induced heart failure with normal ejection fraction in post-heart transplant patients.

AIM Post-heart transplant patients are at increased risk of diastolic dysfunction. The aim of this study was to assess the prevalence of isolated only exercise-induced heart failure with normal ejection fraction (HFNEF) in heart transplant recipients. METHODS AND RESULTS To determine pulmonary capillary wedge pressure (PCWP) at rest and during exercise, 81 patients after orthotopic heart transplantation with normal left ventricular ejection fraction (LVEF) underwent exercise right heart catheterization with simultaneous exercise echocardiography. Based on PCWP values, the patients were divided into three groups. Twenty-one patients had no evidence of HFNEF (PCWP at rest < 15 mmHg, maximal PCWP during exercise < 25 mmHg, prevalence 26%). Forty-seven subjects were found to have only exercise-induced HFNEF (PCWP at rest < 15 mmHg, maximal PCWP during exercise ≥ 25 mmHg, prevalence 58%). Thirteen patients had HFNEF already at rest (PCWP ≥ 15 mmHg at rest, prevalence 16%). Of the noninvasive parameters obtained at rest, multivariate regression analysis identified LV mass index adjusted for allograft age to be an independent predictor of exercise-induced HFNEF. CONCLUSIONS In heart transplant recipients with normal LVEF, there is a high prevalence of exercise-induced HFNEF. LV mass index adjusted for allograft age is predictive of exercise-induced HFNEF.

Pilot study of sex differences in QTc intervals of heart transplant recipients

BACKGROUND Repolarization processes in female and male are different. This study provided pilot data on automatic measurements of QT intervals in heart transplant (HT) recipients stratified according to the sex of the recipient and the donor. METHODS AND RESULTS The following groups were analyzed: Group A-20 males with male heart, group B-14 females with male heart, group C-13 females with female heart, group D-11 males with female heart, group E-20 healthy males, and group F-20 healthy females. Twelve-lead electrocardiograms were digitally captured during autonomic provocative test of five postural 8-minute stages-supine, unsupported sitting, supine, unsupported standing, and supine. Fridericia formula was used for heart rate correction together with a generic correction for QT/RR hysteresis. Neither female nor male HT recipients exhibit any differences in QTc interval duration related to the sex of the donor. There was, however, a trend towards longer QTc intervals in female HT recipients compared to male HT recipients irrespective of the sex of the donor. The QTc differences between healthy control females and males were highly statistically significant proving the assay sensitivity of the study. CONCLUSION The available pilot data suggest that in HT patients, the sex of the donor has little influence on the QTc interval of the transplanted heart.

Monitoring of allograft vasculopathy by intravascular ultrasound one month and one year after heart transplantation: A single center study.

AIMS The aim of this trial was to use intravascular ultrasound (IVUS) to determine whether cardiac allograft vasculopathy (CAV) starts progressing during the first year after heart transplantation (HTx). METHODS We retrospectively analyzed 51 patients (11 women) who received heart transplants in our center between January 2010 and September 2013 and underwent coronary angiography as well as IVUS examination one month and one year after HTx. Patients with proven calcification and fibrotic plates in the IVUS examination one month after HTx constituted a group with defined donor-transmitted atherosclerosis (DTA). In patients without DTA, measurements of maximal intimal thickening (MIT) were made in two predetermined locations. RESULTS Eight of the 51 patients had DTA, while 43 did not. These were divided based on maximal intimal thickness (MIT) into a group with MIT < 0.5 mm (27) and MIT ≥ 0.5 mm (16). No patient with MIT < 0.5 mm developed allograft vasculopathy within one year after HTx. CAV developed in three patients (P = 0.045) out of the 16 patients with MIT ≥ 0.5. In patients with DTA, a statistically significant deterioration in percent area stenosis (PAS) occurred in both artery sections (P = 0.01). CONCLUSION Our trial showed that CAV progresses during the first year after HTx significantly more frequently in patients with DTA and MIT ≥ 0.5 mm. It is essential in these patients to implement an IVUS control examination one year after transplantation. The results can lead to a change in treatment strategy to prevent further progress of the disease.

Decrease in longitudinal strain in heart transplant recipients is associated with rejection

BACKGROUND Around 20-40% of heart transplant patients experience moderate to severe rejection within the first year after heart transplantation. Endomyocardial biopsy (EMB) is a gold standard for diagnosing heart transplant rejection. There is a need for non-invasive alternatives that allow for early, safe and reliable diagnosis of acute graft rejection prior to the onset of clinical symptoms. AIMS Our aim was to investigate the potential of speckle tracking derived strain analysis in the diagnosis of acute graft rejection. METHODS Patients indicated for EMB consented to a trans-thoracic echocardiography examination (TTE) within 2 hours of the EMB. Of this cohort, those with at least 2 EMBs separated ≥ 1 week, and whose TTE could be analyzed for strain, were included. The relationship between strain and EMB results was evaluated. RESULTS Of the 43 patients included (mean age 51.33±1.79, 67% male), 23 had findings of rejection identified on at least one EMB and at least one EMB without rejection for comparison. A significant deterioration in the longitudinal strain during rejection compared to non-rejection was found on apical 4-chamber views (-11.51±0.91 vs -13.48±0.96, P=0.025) and apical 2-chamber views (-11.84±0.78 vs -14.43±0.83, P=0.002). In the patients in whom no rejection was identified on either EBM, there was no significant change in longitudinal strain values at two different time points. CONCLUSION Worsening of longitudinal strain was associated with acute cellular rejection. Routine TTE-based strain analysis could help in early detection of cardiac rejection and timing of EMB.

Quantitative 3D Analysis of Coronary Wall Morphology in Heart Transplant Patients: OCT-Assessed Cardiac Allograft Vasculopathy Progression

&NA; Cardiac allograft vasculopathy (CAV) accounts for about 30% of all heart‐transplant (HTx) patient deaths. For patients at high risk for CAV complications after HTx, therapy must be initiated early to be effective. Therefore, new phenotyping approaches are needed to identify such HTx patients at the earliest possible time. Coronary optical coherence tomography (OCT) images were acquired from 50 HTx patients 1 and 12 months after HTx. Quantitative analysis of coronary wall morphology used LOGISMOS segmentation strategy to simultaneously identify three wall‐layer surfaces for the entire pullback length in 3D: luminal, outer intimal, and outer medial surfaces. To quantify changes of coronary wall morphology between 1 and 12 months after HTx, the two pullbacks were mutually co‐registered. Validation of layer thickness measurements showed high accuracy of performed layer analyses with layer thickness measures correlating well with manually‐defined independent standard (RSymbol = 0.93, Symbolm), average intimal+medial thickness errors were 4.98 ± 31.24 &mgr;m, comparable with inter‐observer variability. Symbol. No caption available. Symbol. No caption available. Quantitative indices of coronary wall morphology 1 month and 12 months after HTx showed significant local as well as regional changes associated with CAV progression. Some of the newly available fully‐3D baseline indices (intimal layer brightness, medial layer brightness, medial thickness, and intimal+medial thickness) were associated with CAV‐related progression of intimal thickness showing promise of identifying patients subjected to rapid intimal thickening at 12 months after HTx from OCT‐image data obtained just 1 month after HTx. Our approach allows quantification of location‐specific alterations of coronary wall morphology over time and is sensitive even to very small changes of wall layer thicknesses that occur in patients following heart transplant.

Is It Important to Reduce the Heart Rate in Patients Early After Heart Transplantation

after cardiac transplantation (CTX) in relation to subsequent prognosis of the patients (pts). Methods: Retrospective analysis of CTX patients operated in one center between 2005-2010 years. EMB findings were correlated with combined end point including treated cellular rejection (ACR), AMR and graft dysfunction. EMBs were performed in prespecified intervals, all samples were evaluated by histology and immunohistochemisty. Banff classification was used for ACR diagnosis, finding of complement fragments C3d, C4d in ≥ 50 % vessels was basis for AMR diagnosis. Graft dysfunction was stated when LVEF decreased ≤ 40 % on echocardiography. Results: During period studied 245 CTX operations were performed. In this study we evaluated the group of 169 pts (129 men), surviving at least 12 months after CTX, with complete data from EMBs available. Fragments of C3d and/or C4d (C) in < 50 % vessels were found in EMBs of 124 (73 %) pts, in 48 % of them in combination. In 55 % of cases this finding was present more than in one EMB series. End-point (EP) was reached in 73 (43 %) of pts. Concordant finding (i.e. positive both C+EP and negative both C+EP) was found in 90 (53 %) of pts. C result predicted occurence of EP with low sensitivity and moderate specificity (48 % resp. 69 %), positive and negative predictive values were 81 % resp. 36 %. Predicted value did not improve when only repeated C positivity was considered. Conclusion: Evidence of complement activation in less than 50 % vesels is frequent EMB finding after CTX. This probably mirrors graft accomodation and is not reliable predictor of rejection and graft dysfunction. Supported by grant MZCR NT 11262-6.