Remifentanil but not sufentanil induces cardioprotection in human ischemic heart muscle in vitro.

BACKGROUND: Previous studies on animal models have suggested that δ-opioid receptor (OR) signaling is the primary pathway responsible for opioids' cardioprotective effect. We hypothesize that the µ-OR's activation protects the human heart muscle. METHODS: We performed the experiments on muscular trabeculae obtained from the right atrial appendages of 104 consecutive patients subjected to coronary artery bypass surgery. Two trabeculae from each patient were studied simultaneously and exposed to 60 min of hypoxia with subsequent 60 min of reoxygenation. Remifentanil (5 µM or 50 µM) or sufentanil (40 µM or 400 µM) was used from the time of reoxygenation. Trabeculae contractility was assessed as the maximal amplitude of the contraction at baseline, after 60 min of hypoxia, during reoxygenation, and after norepinephrine application. RESULTS: During reperfusion, the application of remifentanil improved cardiomyocytes' function as compared to the control group (time from reperfusion: 15 min: 39.8% vs. 21.7%, p = 0.01; 30 min: 41.4% vs. 21.8%, p = 0.01; 60 min: 42.7% vs. 26.9%, p = 0.04; after norepinephrine: 64.7% vs. 43.2%, p = 0.03). The application of sufentanil did not influence cardiomyocyte function as can be seen when comparing the results of the experimental and control group. CONCLUSIONS: Remifentanil, but not sufentanil, induces a cardioprotective effect on human right atria muscle in in vitro conditions, manifested as the increased amplitude of their contraction during reperfusion after 60 min of ischemia.

SARS-CoV-2 infection and SLE: endothelial dysfunction, atherosclerosis, and thrombosis.

An increased risk of atherosclerotic and thrombotic complications characterizes connective tissue diseases. Endothelial dysfunction is the basis for the initiation and progression of atherosclerosis and thrombosis. We present systemic lupus erythematosus (SLE) as a model rheumatic disease with endothelial dysfunction and discuss its mechanisms, factors that influence the early onset and rapid progression of atherosclerosis, and the increased risk of thromboembolic events. We focus on established methods to improve endothelium function, including statins, antiplatelet, and antithrombotic therapy. Hypercoagulable and hypofibrinolitic states and a hyperinflammatory response characterize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Several pathogenic mechanisms are typical for an acute phase of Covid-19 post-Covid syndrome and connective tissue diseases: endothelial dysfunction, elevated antiphospholipid antibody titer, activation of the complement system, and formation of extracellular neutrophil traps (NET). The current review discusses the mechanisms underlying SLE and the COVID-19 in the context of endothelial function, atherosclerosis, and thrombosis (Graphical abstract). Key Points • The pathophysiology of systemic lupus erythematosus (SLE) and Covid-19 shows some similarities, such as endothelial cell activation and dysfunction, the activation of complementary systems, the presence of antiphospholipid antibodies, and the formation of extracellular neutrophil traps. • Autoimmunity in both diseases creates the basis for hyperinflammatory, hypercoagulable, and hypofibrinolitic states and their thromboembolic complications. • This paper presents our perspective on the mechanisms behind the cardiovascular manifestations of SLE and COVID-19, with a particular emphasis on endothelial dysfunction. Covid-19 and systemic lupus erythematosus-potential similarities in pathophysiology. Figures of the panel illustrate the clinical manifestations of endothelial dysfunction, atherosclerosis, and thromboembolism, including coronary artery disease ([A] coronary angiography with left anterior descending artery stenosis and [B] scintigraphy with reduced perfusion in the myocardial apical segments), stroke ([C] carotid angiography, left carotid artery occlusion) and pulmonary embolism ([D]computed tomography with thrombus in the right pulmonary artery).

Arterial stiffness and atherosclerosis in systemic lupus erythematosus patients.

Introduction: Systemic lupus erythematosus (SLE) is characterized by early atherothrombosis. Pulse wave velocity (PWV) is a promising tool for the diagnosis of early vascular remodelling and initial atherosclerotic plaque formation. Our objective was to evaluate PWV and its relationship with coronary atherosclerosis and thrombotic biomarkers in patients with SLE. Material and methods: In 26 patients with SLE with stable clinical conditions, mean age of 39.1 ±11.7 years and without a history of coronary artery disease, multidetector computed tomography (MDCT)-based coronary calcium scoring (CACS) was performed and PWV measured.Laboratory evaluation included serum levels of anticardiolipin and anti-ß2-glycoprotein antibodies (anti-ß2-GPI), lupus anticoagulant (LA), D-dimers, thrombin-antithrombin complexes (TAT), and von Willebrand factor (vWF). Results: Multidetector computed tomography revealed coronary calcifications in 8 (30.8%) patients and the median CACS was 52.4 HU (range 2-843.2). The mean PWV was 9.0 ±3.2 m/s and was higher in patients aged > 50 years (+33.7% vs. < 50 years), those with positive LA (+28.2% vs. LA negative), TAT ≥ 10 µg/l (+18.1% vs. < 10 µg/l), vWF ≥ 200 IU/dl (+51.8% vs. < 200 IU/dl) and with coronary atherosclerosis (CACS > 0; +21.4% vs. CACS = 0).In contrast, the duration of the disease, D-dimers, anticardiolipin, and anti-ß2-GPI antibodies did not influence PWV. In the group without atherosclerosis (CACS = 0, n =18), patients with vWF ≥ 200 IU/dl had a 19.3% higher PWV compared to the rest. Conclusions: In patients with SLE, PWV was associated with the presence of coronary atherosclerotic lesions in MDCT. Furthermore, arterial stiffness was higher in patients with markers of endothelial dysfunction and a prothrombotic state, suggesting their contribution to the early stages of arterial remodelling in SLE.

Influence of statin therapy on antiphospholipid antibodies and endothelial dysfunction in young patients with coronary artery disease and systemic lupus erythematosus.

INTRODUCTION: Antiphospholipid antibodies (aPL) affect atherogenesis and may cause thromboembolism in systemic lupus erythematosus (SLE) and coronary artery disease (CAD). Intensive treatment with statins may reduce inflammation and decrease the number of thrombotic events. That may explain the beneficial effect of statin therapy in SLE and CAD. This study was established to investigate the influence of statin treatment on aPL antibody levels and selected endothelial dysfunction markers in CAD and SLE patients. MATERIAL AND METHODS: Fifty-eight patients - 40 after coronary revascularization (age 38.9 (27-46), 35 males) and 18 with clinically stable SLE (age 38.8 (18-62), 1 male) - were enrolled in the study. In both groups intensive atorvastatin treatment was administered. At baseline and after 1 year of follow-up serology tests were performed: anticardiolipin antibodies (aCL), anti-ß2 glycoprotein I (aß2GPI), lupus anticoagulant (LA), C-reactive protein (CRP), soluble form of intracellular adhesion molecule-1 (sICAM-1), vWF:Ag. RESULTS: Coronary artery disease patients in 1 year follow-up revealed a decrease of aß2GPI IgG and CRP. There was a significant increase in aCL IgG, sICAM-1 and vWF:Ag. In SLE patients aPL levels showed no significant reduction after treatment. CONCLUSIONS: In clinically stable patients IgM and IgG class aß2GPI levels are higher in CAD than in SLE, whereas IgG class aCL levels are lower. Statin treatment decreases the CRP level in both SLE and CAD patients, while decreasing the aß2GPI IgG level only in CAD patients.

Acute myocardial infarction reparation/regeneration strategy using Wharton's jelly multipotent stem cells as an 'unlimited' therapeutic agent: 3-year outcomes in a pilot cohort of the CIRCULATE-AMI trial.

Introduction: CIRCULATE-AMI (NCT03404063), a cardiac magnetic resonance imaging (cMRI) infarct size-reduction-powered double-blind randomized controlled trial (RCT) of standardized Wharton jelly multipotent stem cells (WJMSCs, CardioCell Investigational Medical Product) vs. placebo (2 : 1) transcoronary transfer on acute myocardial infarction (AMI) day ~5-7, is preceded by safety and feasibility evaluation in a pilot study cohort (CIRCULATE-AMI PSC). Aim: To evaluate WJMSC transplantation safety and evolution of left ventricular (LV) remodeling in CIRCULATE-AMI PSC. Material and methods: In 10 consecutive patients (32-65 years, peak CK-MB 533 ±89 U/l, cMRI-LVEF 40.3 ±2.7%, cMRI-infarct size 20.1 ±2.8%), 30 × 106 WJMSCs were administered using a novel cell delivery-dedicated, coronary-non-occlusive method (CIRCULATE catheter). Other treatment was guideline-based. Results: WJMSC transfer was safe and occurred in the absence of coronary (TIMI-3 in all) or myocardial (corrected TIMI frame count (cTFC) 45 ±8 vs. 44 ±9, p = 0.51) flow deterioration or troponin elevation. By 3 years, 1 patient died from a new, non-index territory AMI; there were no other major adverse cardiovascular and cerebrovascular events (MACCE) and no adverse events that might be related to WJMSCs. cMRI infarct size was reduced from 33.2 ±7.6 g to 25.5 ±6.4 g at 1 year and 23.1 ±5.6 g at 3 years (p = 0.03 vs. baseline). cMRI, SPECT, and echo showed a consistent, statistically significant increase in LVEF at 6-12 months (41.9 ±2.6% vs. 51.0 ±3.3%, 36.0 ±3.9% vs. 44.9 ±5.0%, and 38.4 ±2.5% vs. 48.0 ±2.1% respectively, p < 0.01 for all); the effect was sustained at 3 years. Conclusions: CIRCULATE-AMI PSC data suggest that WJMSC transcoronary application ~5-7 days after large AMI in humans is feasible and safe and it may be associated with a durable LVEF improvement. CIRCULATE-AMI RCT will quantify the magnitude of LV adverse remodeling attenuation with CardioCell/placebo administration.

Trans-endocardial delivery of progenitor cells to compromised myocardium using the "needle technique"and risk of myocardial injury.

Introduction: Recent analysis from CHART-1 study indicated that the therapeutic effects of trans-endocardial cardiopoetic cell transplantation in chronic ischemic heart failure (iCHF) may be lost with an increasing number of injections perfomed to deliver therapeutic cells. Aim: To evaluate global and regional contractility and diastolic function of the left ventricle of patients with iCHF who received trans-endomyocardial cardiopoietic stem cells (CSCs) delivery or sham procedures. Material and methods: The study included patients (mean age: 60.8 ±7.1 years) with iCHF (left ventricular ejection fraction (LVEF) < 35%) and a history of hospitalization for worsening heart failure within 12 months despite optimal medical therapy. The patients underwent transmyocardial CSCs transplantation using perforated needle technique or a sham procedure. The wall motion score index (WMSI), LVEF, transmitral E-velocity, E-wave deceleration time, E/A-ratio, and E/e'-mean value were measured with two-dimensional echocardiography on days 1 and 30. Results: A total of 170 segments were analyzed, including 48 targeted segments where 92 injections of 0.5 ml of CSCs were performed. In the transendocardial injections cohort, a decrease in regional contractility was observed in 30.6% (26/85) and 18.9% (16/85) of the segments on days 1 and 30, respectively. This was accompanied by an increase in WMSI by 0.32 ±0.06 and 0.19 ±0.18 (day 1, p = 0.02, day 30, p = 0.03) and a reduction in LVEF (-3.15 ±1.23%, p = 0.065). Conclusions: Transendocardial injections performed to deliver therapeutic cells were associated with myocardial injury. This adverse effect remained, albeit at a lesser degree, at 30-days. Mechanical injury with trans-endocardial delivery of progenitor cells using the "needle technique" may counterbalance, at least in part, any cell-related benefit(s).

Endothelial dysfunction in obstructive sleep apnea patients.

PURPOSE: Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for cardiovascular diseases. The aim of the study was to assess the influence of OSAS on endothelial dysfunction and thrombosis biomarkers and to evaluate the effect of treatment with continuous positive airway pressure (CPAP) on biomarker levels. METHODS: NT-proBNP, sICAM-1, endothelin-1, von Willebrand factor, D-dimers, and thrombin-antithrombin complex (TAT) were measured in 50 patients diagnosed with moderate-to-severe OSAS. All patients underwent transthoracic echocardiography, and 38 months after the inclusion, 16 CPAP users and 22 non-CPAP users were reassessed. RESULTS: Sleep-related indices of apnea-hypopnea index (AHI) and mean SpO2 were associated with higher sICAM-1 levels (AHI < 30: 7.3 ± 4.7 vs. AHI ≥ 30: 19.5 ± 19.4 mg/ml, p = 0.04; SpO2 ≥ 90%: 11.9 ± 9.3 vs. SpO2 < 90%: 23.6 ± 25.8, p = 0.04). sICAM-1 levels were significantly higher in obese patients, particularly with BMI ≥ 40. Plasma levels of TAT were significantly correlated with the increased right ventricular size (right ventricular diameter ≤ 37 mm: 0.86 ± 0.70 vs. > 37 mm: 1.96 ± 1.20 ng/ml, p = 0.04). Endothelin-1 levels were higher in patients with decreased right ventricular function (right ventricle TDI-derived S' ≥ 12 cm/s: 11.5 ± 10.9 vs. < 12 cm/s: 26.0 ± 13.2 pg/ml, p = 0.04). An increase in NT-proBNP was related to impaired parameters of the right ventricular contractile function. There were no correlations between long-term CPAP therapy and the levels of biomarkers. CONCLUSION: Severe OSAS influences endothelial damage as manifested by an increase in sICAM-1 levels. Changes in right ventricular structure and function, observed mainly in patients with higher TAT and endothelin-1 levels, are also manifested by an increase in NT-proBNP levels. Long-term CPAP treatment does not seem to influence biomarkers in patients with moderate-to-severe OSAS, which may help to explain the lack of influence of CPAP on cardiovascular risk reduction.

Continuous positive airway pressure treatment in sleep apnea: patient compliance and impact on the right heart.

Obstructive sleep apnea syndrome (OSAS) is considered to be an important predisposing factor for cardiovascular diseases. The main objective of this study was to investigate the impact of CPAP treatment on cardiac structure and function and to assess patient compliance over a long-term course of CPAP treatment. A total of 50 patients diagnosed with moderate-to-severe OSAS based on overnight study, without relevant concomitant diseases were enrolled. Patient compliance, along with echocardiographic and CPAP parameters, was assessed. The average time to follow-up was 38 ± 4.2 months. An increase in tricuspid annular plane systolic excursion (TAPSE) (22.1 ± 4.3-25.5 ± 4.6 mm, p = 0.005) and peak early systolic tricuspid annular velocity (S') (14 ± 3.2-17.2 ± 5.2 cm/s, p = 0.005) after CPAP treatment was noted. In patients without CPAP, no significant change in right ventricular (RV) contractility was found. There were no significant differences regarding right atrial (RA) and RV diameters, as well as tricuspid regurgitant peak gradient (TRPG) in both groups; however, a predisposition to increased RA size along with RV and tricuspid annulus diameters was revealed. The mean duration of nightly CPAP use was 3 ± 2.3 h/night in all-day analysis and 4.7 ± 2.1 h/night on days with device usage. The non-adherence rate was 57%. The use of effective CPAP therapy may lead to increased RV systolic function in patients with OSAS in long-term observation. However, long-term patient compliance is generally poor. Regardless of CPAP therapy, a gradual increase in heart size is observed.

Mitral regurgitation severity dynamic during acute decompensated heart failure treatment.

Acute decompensated heart failure (ADHF) treatment leads to significant hemodynamic changes. The aim of our study was to quantitatively analyze the dynamics of mitral regurgitation (MR) severity (evaluated by transthoracic echocardiography) which occur during the treatment of ADHF and to correlate these changes with the clinical condition of patients as well as heart failure biochemical markers. The study included 27 consecutive adult patients (40.7% females, mean age 71.19 ± 11.2 years) who required hospitalization due to signs of acute HF. Echocardiographic assessment was performed upon admission and discharge together with clinical and laboratory evaluation. Significant reduction in dyspnea intensity [0-100 scale] (81.48 ± 9.07 vs. 45.00 ± 11.04 pts, p < 0.001), body weight (84.98 ± 18.52 vs. 79.77 ± 17.49 kg, p < 0.001), and NT-proBNP level (7520.56 ± 5288.62 vs. 4949.88 ± 3687.86 pg/ml, p = 0.001) was found. The severity of MR parameters decreased significantly (MR volume 44.92 ± 22.83 vs. 30.88 ± 18.77 ml, p < 0.001; EROA 0.37 ± 0.17 vs. 0.25 ± 0.16 cm2, p < 0.001; VC 6.21 ± 1.48 vs. 5.26 ± 1.61 mm, p < 0.001). Left atrial area (35.86 ± 9.11 vs. 32.47 ± 9.37, p < 0.001) and mitral annular diameter (42.33 ± 6.63 vs. 39.72 ± 5.05. p < 0.001) also underwent statistically significant reductions. An increase in LVEF was observed (34.73 ± 13.88 vs. 40.24 ± 13.19%, p < 0.001). In 40.7% of patients, a change in MR severity class (transition from a higher class to a lower one) was observed: 6/8 (75%) patients transitioned from severe to moderate and 6/18 (33.3%) patients transitioned from moderate to mild class. Treatment of ADHF leads to a significant reduction in MR severity, together with significant reductions in left atrial and mitral annular dimensions. Quantitative measurement of MR dynamics offer valuable assistance for ADHF management.

Influence of obstructive sleep apnea on right heart structure and function.

INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is a highly prevalent sleep disorder associated with increased cardiovascular morbidity and mortality. This study aimed to investigate heart structure and function and their correlation with the degree of OSAS and sleep indexes in patients diagnosed with OSAS. MATERIALS AND METHODS: A cohort of 77patients (48 males, aged 58.1 ± 11.0 years, body mass index [BMI] = 32.4 ± 6.2) admitted to the hospital due to suspected OSAS was examined using echocardiography and polysomnography. RESULTS: Patients with moderate-to-severe OSAS compared to patients without diagnosed OSAS or with mild OSAS had greater right ventricular outflow tract (RVOT) dimensions (32.6 ± 3.6 vs 30.9 ± 2.4 mm; p < 0.05), larger right atrial area (RAA; 21.1 ± 4.8 vs 17.2 ± 3.2 mm; p = 0.002), greater right ventricular mid-cavity diameter (RVD; 35.5 ± 7.0 vs 32.2 ± 4.7 mm; p = 0.02), and diminished tricuspid annular plane systolic excursion (TAPSE, 21.9 ± 4.5 vs 25.8 ± 4.4 mm; p = 0.04), while there were no significant differences in tissue doppler imaging (TDI) parameters (S' and E') and in valvular regurgitation gradient for both groups. Moreover, significantly greater RVOT dimensions (31.6 ± 2.6 vs 30.9 ± 3.0 mm, p = 0.04), RVD (39.3 ± 7.0 vs 32.7 ± 5.2 mm, p = 0.003), and RAA (21.4 ± 4.4 vs 18.1 ± 4.2 mm, p = 0.02) as well as reduction in TAPSE (20.9 ± 5.3 vs 25.0 ± 4.3 mm, p = 0.01) were observed in patients having ≥ 10 episodes of obstructive apnea (OA) per hour. CONCLUSIONS: In moderate-to-severe OSAS patients, right ventricular (RV) enlargement was observed together with RV dysfunction as measured by TAPSE. Examination using TDI is not superior to standard echocardiography for the detection of heart pathology in OSAS patients. Right heart pathology is present predominantly in patients with obstructive apnea.

Chronotropic incompetence causes multiple organ complications in adults after the Fontan procedure.

BACKGROUND: Although patients undergoing the Fontan procedure (FP) present a normal or close­to­­normal function of the systemic ventricle, they cannot generate cardiac output or exhibit similar exercise capacity as their healthy peers. This can be attributed to chronotropic incompetence and multiple organ complications. AIMS: We evaluated the prevalence of chronotropic incompetence in adults after FP and assessed the relationship between heart rate reserve (HRR) and multiple organ complications. METHODS: Data were obtained from 50 post­FP patients (mean [SD] age, 27 [6.6] years) and 30 healthy controls matched for age and sex. All patients were subjected to clinical examination, laboratory tests, echocardiography, cardiopulmonary exercise test, and chronotropic function evaluation. RESULTS: Cardiopulmonary exercise test parameters were impaired in the post­FP group. Chronotropic incompetence was identified in 46 patients (92%), who also had a lower median (interquartile range) chronotropic index (0.55 [0.47-0.62] vs 0.93 [0.88-0.99]; P <0.001) and a greater median (interquartile range) HRR (32 [24-60] bpm vs 8 [1-14] bpm, P <0.001). A negative correlation was observed between HRR and peak oxygen uptake, and a positive one between HRR and the peak ventilatory equivalent for CO2 and mean platelet volume. The study revealed the diagnostic utility of HRR in detecting an abnormal peak ventilatory equivalent for O2, alkaline phosphatase levels, the ratio of aspartate transaminase to alanine transaminase levels, and mean platelet volume. CONCLUSIONS: Chronotropic incompetence correlates with impaired exercise capacity, liver dysfunction, and platelet abnormalities in post­FP patients. Heart rate reserve may be a promising indicator of organ complications as well as a sign of future bradyarrhythmia and the need for cardiac pacing.

Prognostic role of traditional cardiovascular risk factors in patients with idiopathic pulmonary arterial hypertension.

INTRODUCTION: Metabolic alterations have been recently associated with onset and progression of idiopathic pulmonary arterial hypertension (IPAH). We aimed to determine the prevalence and prognostic role of cardiovascular risk factors in patients with IPAH. MATERIAL AND METHODS: Between February 2009 and January 2015 we recruited consecutive IPAH patients. Clinical assessment included medical history, fasting glucose, lipid profile, N-terminal pro-brain natriuretic peptide concentration, 6-minute walk test distance, WHO functional class and hemodynamic evaluation. Patients' risk was estimated based on the Swedish PAH Register grading system. RESULTS: The study group included 61 IPAH patients, and the control group included 2413 Polish residents. When compared to the general population, IPAH patients had lower low-density lipoprotein cholesterol (LDL-C) and a higher triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio. Female patients were characterized by elevated glucose level, higher prevalence of diabetes and lower HDL-C than controls. PAH severity grade correlated positively with age and TG/HDL-C ratio (R = 0.29, p = 0.02) and inversely with LDL-C (R = -0.28, p = 0.03) and HDL-C (R = -0.39, p = 0.02) concentrations. After a follow-up of 48 (23-79) months we recorded 28 deaths in the IPAH group. In the regression analysis lower LDL-C (p = 0.002) and HDL-C (p = 0.0002) levels, and higher TG/HDL-C ratio (p = 0.003) and glucose level (p = 0.003) were associated with all-cause mortality after adjustment for age, sex or PAH severity grade. CONCLUSIONS: Patients with IPAH are characterized by an altered profile of lipid and glucose metabolism. Lowered levels of LDL-C and HDL-C and increased TG/HDL-C ratio correlate with disease severity and together with elevated plasma glucose level predict poor survival in IPAH.

Long-term follow-up in adults after tetralogy of Fallot repair.

BACKGROUND: Tetralogy of Fallot (ToF) is the most common cyanotic congenital heart disease and the population of ToF repair survivors is growing rapidly. Adults with repaired ToF develop late complications. The aim of this study was to describe and analyze long-term follow-up of patients with repaired ToF. METHODS: This is a retrospective cohort study. Consecutive 83 patients with repaired ToF who did not undergo pulmonary valve replacement were included. Mean age of all patients was 30.5 ± 10.7. There were 49 (59%) male. Patients were divided into two groups according to the time since the repair (< 25 years and ≥ 25 years). The electrocardiographic (ECG), cardiopulmonary exercise testing (CPET), echocardiographic and cardiac magnetic resonance (CMR) data were reviewed retrospectively. RESULTS: In CPET values were not significantly different in the two groups. In CMR volumes of left and right ventricles were not significantly different in the two groups. There were no differences between the groups in ventricular ejection fraction, mass of ventricles, or pulmonary regurgitation fraction. Among all the patients, ejection fraction and left and right ventricle mass, indexed pulmonary regurgitation volume measured by CMR did not correlate with the time since repair. In ECG among all the patients, ejection fraction of the RV, measured in CMR, negatively correlated with QRS duration (r = - 0.43; p < 0.001). There was a positive correlation between QRS duration and end diastolic volume of the RV (r = 0.30; p < 0.02), indexed end diastolic volume of the RV (r = 0.29; p = 0.04), RV mass (r = 0.36; p < 0.001) and left ventricle mass (r = 0.26; p = 0.04). CONCLUSION: Long-term survival and clinical condition after surgical correction of ToF in infancy is generally good and the late functional status in ToF - operated patients could be excellent up to 25 years after the repair. QRS duration could be an utility and easy factor to assessment of right ventricular function. TRIAL REGISTRATION: The study protocol was approved by the local Ethics Committee. Each participant provided informed consent to participate in the study (license number 122.6120.88.2016 from 28.04.2016).

Opioidergic conditioning of the human heart muscle in nitric oxide-dependent mechanism.

BACKGROUND: Opioidergic conditioning is well documented to trigger cardioprotection against ischemia/ reperfusion (I/R) injury. Previous studies on animal models have suggested that nitric oxide (NO) mediates the beneficial effect of opioids, but the role of NO in humans seems to be controversial. OBJECTIVES: The aim of the study was to assess the influence of NO modulators on opioid-induced cardioprotection in the human myocardium. MATERIAL AND METHODS: Trabeculae of the human right atria were electrically driven in an organ bath and subjected to simulated I/R injury. The non-selective inhibitor of nitric oxide synthase (NOS) - N-methyl-l-arginine (LNMMA), the donor of NO - S-Nitroso-N-acetylpenicillamine (SNAP) or morphine (in the amount of 10-4 M) were used at the time of re-oxygenation. The additional trabecula was subjected to the hypoxia protocol only (control). The contractility of the myocardium was assessed as the maximal force of a contraction (Amax), the rate of rise of the force of a contraction (Slope L) and the cardiac muscle relaxation - as the rate of decay of the force of a contraction (Slope T). RESULTS: The application of 100 µM LNMMA resulted in the decrease of Amax, Slope L and Slope T during the re-oxygenation period as compared to control. The application of 10-4 M morphine and/or 100 µM SNAP resulted in a partial reversal of the detrimental influence of LNMMA. CONCLUSIONS: At the re-oxygenation period, the blockade of NO synthesis has a deleterious effect on the systolic and diastolic function of the human myocardium as well as attenuates the beneficial effect of morphine conditioning.

Ischemic Versus Non-Ischemic (Neurogenic) Myocardial Contractility Impairment in Acute Coronary Syndromes: Prevalence and Impact on Left Ventricular Systolic Function Recovery.

BACKGROUND Neurogenic mechanism is believed to contribute to left ventricular (LV) systolic dysfunction in acute coronary syndromes (ACS); its extreme form is known as takotsubo cardiomyopathy. However, the magnitude of neurogenic contribution to LV dysfunction in all-comer first-time ACS remains unknown. MATERIAL AND METHODS In 120 consecutive patients with first-time ACS (age 66.3±12.3years, 40 women) coronary angiograms were individually matched to the echocardiographic left ventricular (LV) segments (17-segment model). Baseline contractility impairment was classified as ischemic (I): confined to the stenotic artery(ies) supply area(s), neurogenic (N): in absence of attributable coronary stenosis, or partially ischemic/partially neurogenic (I&N). Echocardiography was repeated at 6 months to determine LV systolic function recovery. RESULTS Neurogenic component (NC) contribution to myocardial contractility impairment was present in 24.2% of ACS patients, with pure N in 6.7% and I&N in 17.5%. Diabetes/pre-diabetes was present in 38.5% vs. 33.5% vs. 0% (I vs. I&N vs. N; p=0.02). Major stressor preceding symptom onset was reported in 3.3% in I, 9.5% in I&N, and 25.0% in N (p=0.03). The number of LV segments with contractility impairment was 2±4 in I, 17±11 in I&N, and 3±16 in N (p<0.05). NC presence was independently associated with better recovery of global LV systolic function (OR 2.99, 95% CI: 1.16-7.76; p=0.024). CONCLUSIONS Novel findings from this study are: (1) NC may contribute to myocardial contractility impairment in 1 in every 4 first-time ACS patients, (2) NC contribution to contractility impairment in ACS is blunted in diabetes or pre-diabetes, and (3) LV systolic function recovery is better in patients with NC.

Long-Term Effects of Percutaneous Fenestration Following the Fontan Procedure in Adult Patients with Congenital Univentricular Heart.

BACKGROUND The Fontan procedure, performed for univentricular heart, may also include the technique of percutaneous fenestration to create a small atrial septal defect (ASD) and a right-to-left shunt. The aim of this study was to evaluate the long-term effects of fenestration in adult patients who had a Fontan procedure for univentricular heart. MATERIAL AND METHODS Fontan surgery was performed in 39 patients, including 19 (49%) patients with fenestration (Group I), and 20 (51%) patients without the fenestration procedure (Group II). Laboratory tests in both groups included echocardiography, plethysmography, cardiopulmonary exercise testing, and 24-hour Holter monitoring. RESULTS Compared with patients in Group I, patients in Group II had a significantly increased level of N-terminal pro-brain natriuretic peptide (NT-proBNP) (p=0.04), alkaline phosphatase (ALP) (p=0.01) and a significant increase in frequency of atrial fibrillation (p=0.04). Patients in Group I had a significantly increased systemic ventricular ejection fraction (SVEF) (p=0.05) and increased heart rate (HR) (p=0.006), heart rate reserve (HRR) (p=0.02), ventilatory equivalent (VE) (p=0.01), and VO2 peak (p=0.05) on cardiopulmonary exercise testing (CPET). Renal, hematologic, and ventilatory parameters, and incidence of thromboembolism showed no significant differences between the groups. CONCLUSIONS Long-term follow-up of patients who underwent Fontan procedures with percutaneous fenestration had improved single ventricular function, lower NT-proBNP levels, improved exercise capacity, and reduced ALP levels. These findings indicate that percutaneous fenestration closure should be considered for adult patients who have undergone Fontan procedure for univentricular heart.

Influence of autoimmunity and inflammation on endothelial function and thrombosis in systemic lupus erythematosus patients.

The aim of this study is to assess the relationship between autoimmunity and endothelial activation/damage (ICAM-1 and vWF serum levels) and the degree of prothrombotic activity (thrombin-antithrombin complexes-TAT serum levels) in SLE. In 60 clinically stable SLE patients, levels of the following parameters were estimated in their serum: lupus anticoagulant (LA), anticardiolipin antibodies in both IgG and IgM classes (aCL-IgG and aCL-IgM, respectively), antiß2GPI antibodies in both IgG and IgM classes (antiß2GPI-IgG and antiß2GPI-IgM, respectively), ICAM, von Willebrand factor (vWF), TAT, CRP, C3c, C4, and IL-6. ICAM-1 values exceeded the upper reference limit in 9 (15%) patients. vWF levels were increased in 21 (35%) patients. In all patients with elevated ICAM-1 values, vWF were also increased. TAT concentrations were elevated in 12 (20%) people. ICAM-1 were significantly higher in patients with elevated aCL-IgM (> 30 MPL vs ≤ 30 MPL; p < 0.05). Similarly, ICAM-1 were significantly higher in patients with elevated antiß2-GPI-IgM (> 20 SMU vs ≤ 20 SMU; p < 0.05). There was no significant difference in ICAM-1 levels in relation to LA-positivity. vWF were not significantly different in relation to antiphospholipid antibodies nor the inflammation marker levels. TAT were significantly higher in patients with elevated aCL-IgM (> 30 MPL vs ≤ 30 MPL; p < 0.05). In one third of young patients with stable SLE, signs of endothelial activation/damage were found, as shown by elevated plasma ICAM-1 or vWF. Increased prothrombotic tendency manifested by elevated TAT was found in one fifth of the patients. Elevated anticardiolipin (IgM) and anti-ß2-glycoprotein I (IgM) antibodies influence endothelial dysfunction and enhance prothrombotic state.

What determines the quality of life of adult patients after Fontan procedure?

BACKGROUND: Despite the low early mortality of Fontan procedures, Fontan patients are prone to vari-ous cardiac and extra-cardiac complications in the long term. This may influence patient perception of their health and outcome. The aim of the study was to assess the relationship of multi-organ compli-cations and physical efficiency with self-reported health-related quality of life (QOL) in adult Fontan patients. METHODS: Quality of life was assessed with the Short Form-36 questionnaire. Laboratory tests were done together with echocardiography, plethysmography, and cardiopulmonary exercise test. RESULTS: The QOL was poorer in patients than in control subjects. The physical characteristics of patients correlated with dynamic ventilatory parameters, heart rate at the peak of exercise, alanine aminotransferase and albumin level. CONCLUSIONS: Liver impairment and chronotropic incompetence during exercise are associated with poor QOL in patients after Fontan procedure. In these patient, hepatic, pulmonary and cardiac functions should be carefully monitored. (Cardiol J 2018; 25, 1: 72-80).

Ischemic conditioning of human heart muscle depends on opioid-receptor system.

BACKGROUND: Despite progress in the invasive treatment of ischemic heart disease, the ability to limit ischemia-reperfusion (I/R) injury remains largely unrealized. Ischemic pre-conditioning (IPC) and post-conditioning (POC) induce the protective mechanisms of resistance against I/R injury. Stimulation of opioid receptors mimic the protective effect of IPC or POC in an animal models. We tested the hypothesis, that IPC and POC provide cardioprotection in opioid-dependent mechanism in human myocardium. METHODS: Human atrial trabeculae were subjected to I/R injury. To achieve IPC, single hypoxia period preceded the applied lethal hypoxia, to achieve POC triple hypoxia periods followed lethal hypoxia. Naloxone was used at the onset of lethal hypoxia in IPC protocol, and at the time of re-oxygenation in POC protocol. Contractive function of the myocardium was assessed as maximal force of contraction (Amax), rate of rise of force of contraction (+dV/dT) and diastolic parameter - rate of decay of force of contraction (-dV/dT). RESULTS: Co-application of naloxone with IPC or POC resulted in decrease of Amax, +dV/dT and -dV/dT during re-oxygenation period as compared to IPC or POC only. CONCLUSIONS: Naloxone abrogates beneficial effect of IPC and POC. IPC and POC in humans provide cardioprotection in opioid receptor system dependent mechanism.