Differential gene expression of leaflet tissue in chronic ovine functional tricuspid regurgitation.

OBJECTIVES: Severe functional tricuspid regurgitation (FTR) is associated with subvalvular remodelling, but leaflet tissue alterations may also contribute. We set out to investigate molecular mechanisms driving leaflet remodelling in chronic ovine FTR. METHODS: Thirteen adult sheep (55 ± 4kg) underwent left thoracotomy, epicardial echocardiography, and pulmonary artery banding (PAB) to induce right heart failure and FTR. After 16 weeks, 13 banded (FTR) and 12 control (CTL) animals underwent median sternotomy for epicardial echocardiography and were subsequently sacrificed with each tricuspid leaflet tissue harvested for RNA-seq and histology. RESULTS: After 16 weeks, 7 animals developed severe, 2 moderate, and 4 mild tricuspid regurgitation (TR). Relative to CTL, FTR animals had increased PAP, TR, tricuspid annular diameter, and right atrial volume, while tricuspid annular plane systolic excursion (TAPSE) and RV fractional area change decreased. FTR leaflets exhibited altered constituents and an increase in cellularity. RNA-seq identified 85 significantly differentially expressed genes (DEG) with 17, 53, and 127 within the anterior, posterior, and septal leaflets respectively. RRM2, PRG4, and CXCL8 (IL-8) were identified as DEGs across all leaflets and CXCL8 was differentially expressed between FTR severity grades. RRM2, PRG4, and CXCL8 significantly correlated with TAPSE, and this correlation was consistent regardless of the anatomical location of the leaflet. CONCLUSIONS: PAB in our ovine model resulted in RV failure and FTR. Leaflet RNA-seq identified several DEGs, specifically RRM2, PRG4, and CXCL8, with known roles in tissue remodelling. These data along with an overall increase in leaflet cellularity suggest tricuspid leaflets actively remodel in FTR.

Sleeping Disorders in Healthy Individuals with Different Dietary Patterns and BMI, Questionnaire Assessment.

The COVID-19 pandemic and abiding restrictions have affected every life domain. Sleep disturbances are a major health issue that is linked with a higher prevalence of metabolic syndrome, obesity, and psychological burdens. Research of sleeping disorders among vegetarian and non-vegetarian subpopulations is limited. The aim of the study was to assess the prevalence of sleeping disorders during the COVID-19 pandemic among people with different dietary patterns. Using a web-based cross-sectional survey, data were collected from 1987 people. A total of 1956 respondents met all study conditions. The questionnaire consisted of sociodemographic information, assessment of dietary habits, and assessment of the prevalence of insomnia and sleepiness, based on the Athens Insomnia Scale (AIS) and Epworth Sleepiness Scale (ESS). A total of 36.04% (n = 705) respondents declared that they noticed a change in the quality of their sleep during the last year. According to AIS and ESS, non-vegetarians suffered from insomnia or sleepiness more often than vegetarians. Insomnia and sleepiness were also more prevalent among those respondents who declared consumption of fruit and vegetables less often than once a day compared with those who consumed fruit and vegetables daily. Respondents with BMI within the recommended limit (18.5-24.99) suffered from insomnia less often when compared with underweight (BMI < 18.5) or obese (BMI ≥ 25) respondents. Those results may be useful for public health workers and medical professionals in terms of establishing new instruments that help treat sleeping disorders.

Open aortic arch surgery: 10 years' single-center experience.

INTRODUCTION: Open aortic arch surgery is a complex cardiac surgical procedure. AIM: We reviewed the 10-year outcomes of elective aortic arch aneurysm surgery in a single cardiac surgical center. MATERIAL AND METHODS: The analysis includes all patients who underwent elective aortic arch surgery at our institution between January 2010 and December 2020. The study population was divided into group A consisting of patients operated on during the first 5 years, and group B, including patients operated on during the subsequent 5 years. The groups were compared with regard to baseline characteristics, scope of the surgery, operative and postoperative data as well as morbidity and mortality. RESULTS: Eighty-six elective aortic arch procedures were performed during the analyzed period, including 25 (29%) patients in group A and 61 (71%) patients in group B. The hemiarch procedure was more frequently performed in group A (17 patients, 68%) in comparison to group B (21 patients, 34%) (p = 0.008). Stroke was recorded in 6 (20%) patients from group A and 5 (8.2%) patients from group B (p = 0.002). Five-year survival was 60 ±9.8% for group A, and 81 ±6.2% for group B (log-rank test, p = 0.003). CONCLUSIONS: After completion of the learning curve, open aortic arch surgery is associated with acceptable early mortality, low incidence of stroke, and a high 5-year survival rate.

Assessment of adrenal reserve and secretion of cortisol in patients over 60 years of age undergoing cardiac surgery.

INTRODUCTION: Cortisol level affects the prognosis of patients after cardiac surgery. Meanwhile, there are no clear guidelines for steroid supplementation after a cardiac operation. The relationship between age and blood cortisol levels has not been finally clarified. AIM: Assessment of adrenal reserve and secretion of cortisol in patients over 60 years of age undergoing cardiac surgery. MATERIAL AND METHODS: The study included 20 patients of both sexes referred for cardiac surgery. A short ACTH synthetic stimulation test was carried out. Assessment of cortisol secretion was carried out in the morning on the day of surgery and the 1st, 2nd and 4th days after surgery in blood samples. RESULTS: A result within the normal range for the adrenal reserve was found in 19 of the 20 patients enrolled in the study. The short Synacthen test predicted postoperative secretion of cortisol (p = 0.04, r = 0.047). A relationship between secretion of cortisol and patients' age was observed (p = 0.03, r = 0.48). The concentration of cortisol on the 1st postoperative day was correlated with the total dose of dopamine (p = 0.006, r = 0.58) and adrenaline (p = 0.04, r = 0.47). The concentration of cortisol on the day of the surgery correlated with the lactate concentration on day 2 (p = 0.04, r = 0.45). The concentration of lactates on day 1 correlated with total dose of dopamine (p = 0.01, r = 0.54). CONCLUSIONS: A short Synacthen test allows one to predict secretion of cortisol after cardiac surgery. Greater secretion of cortisol after cardiac surgery may be associated with a more difficult postoperative course. There was no decrease in cortisol secretion with age.

Can human myocardium be remotely preconditioned? The results of a randomized controlled trial.

OBJECTIVES: No experimental study has shown that the myocardium of a remotely preconditioned patient is more resistant to a standardized ischaemic/hypoxic insult. METHODS: This was a single-centre randomized (1:1), double-blinded, sham-controlled, parallel-group study. Patients referred for elective coronary bypass surgery were allocated to either remote ischaemic preconditioning (3 cycles of 5-min ischaemia/5-min reperfusion of the right arm using a blood pressure cuff inflated to 200 mmHg) or sham intervention. One hundred and thirty-four patients were recruited, of whom 10 dropped out, and 4 were excluded from the per-protocol analysis. The right atrial trabecula harvested on cannulation for cardiopulmonary bypass was subjected to 60 min of simulated ischaemia and 120 min of reoxygenation in an isolated organ experiment. Postoperative troponin T release and haemodynamics were assessed in an in vivo study. RESULTS: The atrial trabeculae obtained from remotely preconditioned patients recovered 41.9% (36.3-48.3) of the initial contraction force, whereas those from non-preconditioned patients recovered 45.9% (39.1-53.7) (P = 0.399). Overall, the content of cleaved poly (ADP ribose) polymerase in the right atrial muscle increased from 9.4% (6.0-13.5) to 19.1% (13.2-23.8) (P < 0.001) after 1 h of ischaemia and 2 h of reperfusion in vitro. The amount of activated Caspase 3 and the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells also significantly increased. No difference was observed between the remotely preconditioned and sham-treated myocardium. In the in vivo trial, the area under the curve for postoperative concentration of troponin T over 72 h was 16.4 ng⋅h/ml (95% confidence interval 14.2-18.9) for the remote ischaemic preconditioning and 15.5 ng⋅h/ml (13.4-17.9) for the control group in the intention-to-treat analysis. This translated into an area under the curve ratio of 1.06 (0.86-1.30; P = 0.586). CONCLUSIONS: Remote ischaemic preconditioning with 3 cycles of 5-min ischaemia/reperfusion of the upper limb before cardiac surgery does not make human myocardium more resistant to ischaemia/reperfusion injury. CLINICAL TRIAL REGISTRATION NUMBER: NCT01994707.

Remote Ischaemic PrEconditioning of Human Myocardium (RIPE): study protocol for a double-blinded randomised controlled trial.

BACKGROUND: Remote preconditioning has been shown to be a potent protective phenomenon in many animals. Several studies aimed to demonstrate it was feasible in humans by trying to show its protective effect during cardiac surgery. Of these, some small studies and one larger trial were positive while two other bigger studies showed no effectiveness of remote preconditioning as assessed by levels of postoperatively released cardiac markers. Recently, two large clinical trials also failed to prove the benefit of remote preconditioning in cardiac surgery. No study showed that remote preconditioning actually increases resistance of human myocardium to standardised ischaemic and reperfusion stimulus in experimental settings. In animal studies, remote preconditioning was shown to improve mitochondrial function and structure, but such data on human myocardium are scarce. AIM: The aim of the study is to determine whether remote preconditioning protects human myocardium against ischaemia-reperfusion injury in both in vivo and in vitro conditions. METHODS: The trial is designed as a single-centre, double-blinded, sham-controlled trial of 120 patients. We randomise (1:1) patients referred for coronary artery bypass grafting for stable coronary artery disease to remote preconditioning or "sham" intervention. The remote preconditioning is obtained by three cycles of 5 min inflation and 5 min deflation of a blood pressure cuff on the right arm. Postoperative course including myocardial enzymes profile will be analysed. Moreover, in the in-vitro arm the clinically preconditioned myocardium will be assessed for function, mitochondria structure, and mitochondria-dependent apoptosis. The informed consent of all patients is obtained before enrolment into the study by the investigator. The study conforms to the spirit and the letter of the declaration of Helsinki. RESULTS AND CONCLUSIONS: In case the effect of remote preconditioning is not measurable in ex-vivo assessment, any future attempt at implementing this phenomenon in clinical practice may be futile and should not be continued until the effect can be confirmed in a controlled experimental setting. The study might therefore indicate future directions in trials of clinical implementation of remote preconditioning. TRIAL REGISTRATION: Clinical Trials Register (Clinicaltrials.gov) identifier: NCT01994707. The study was approved by Institutional Review Board of the Medical University of Silesia (KNW/0022/KB1/160/12).

Postoperative serum troponin T concentration in patients undergoing aortic valve replacement does not predict early postoperative outcome.

BACKGROUND: The measurement of serum cardiac troponin T concentration (cTnT) after aortic valve replacement (AVR) provides the opportunity to assess the degree of myocardial damage and may have some prognostic value. AIM: To determine whether elevated troponin level is related to patient outcome. METHODS: We investigated patient outcome and postoperative serum concentration of troponin T in 79 patients who underwent AVR. Serum levels of cTnT were measured within 24 h of AVR. We searched for the occurrence of subsequent adverse events i.e. requirement for intraaortic ballon pump (IABP) or inotropic support, prolonged Intensive Care Unit (ICU) stay, and in-hospital death. RESULTS: Serum concentration of cTnT after AVR increased significantly compared to the preoperative value. We found significant positive correlations between aortic cross-clamp time (r = 0.23, p = 0.04), cardiopulmonary bypass time (r = 0.4,p = 0.00029), duration of the surgery (r = 0.30, p = 0.008), and postoperative cTnT level. Three (4%) patients required IABP support, 37 (46%) patients required inotropic support, and 11 (14%) patients had a prolonged ICU stay (> 48 h). Thirty eight (48%) patients required either inotropic support or IABP insertion. At least one adverse event occurred in 44 (56%) patients. Median postoperative serum cTnT concentration was 0.31 ng/mL (interquartile range 0.23-0.60 ng/mL). We failed to find a statistically significant difference in postoperative cTnT level between patients with and without adverse events. According to multiple logistic regression analysis, the postoperative serum level of troponin T was not independently associated with adverse patient outcome. Diabetes mellitus, patient age and left ventricular ejection fraction below 50% were significant independent predictors of adverse events after AVR. The area under receiver operating curve (AUROC) for postoperative serum troponin T concentration as a determinant of various adverse outcomes was never significantly different from 0.50. CONCLUSIONS: Serum cTnT concentration is frequently - if not universally - elevated after AVR. Serum level of troponin T measured on the first postoperative morning is a poor predictor of patient outcome after AVR and should not be relied on when planning postoperative care.