Tomasz Hirnle

Myocardium of type 2 diabetic and obese patients is characterized by alterations in sphingolipid metabolic enzymes but not by accumulation of ceramide

Data from animal experiments strongly suggest that ceramide is an important mediator of lipotoxicity in the heart and that accumulation of ceramide contributes to cardiomyocyte apoptosis associated with type 2 diabetes and obesity. However, it remains unknown whether a similar relationship is present also in the human heart. Therefore, we aimed to examine whether myocardial apoptosis in obese and type 2 diabetic patients is associated with elevated ceramide level. The study included 11 lean and 26 overweight or moderately obese subjects without (n = 11, OWT) or with (n = 15, T2D-OWT) a history of type 2 diabetes. Samples of the right atrial appendage were obtained from patients at the time of coronary bypass surgery. Compared with lean subjects, the extent of DNA fragmentation (a marker of apoptosis) was significantly higher in the myocardium of OWT patients and increased further in T2D-OWT subjects. However, the content of ceramide and sphingoid bases remained stable. Interestingly, the mRNA level of enzymes involved in synthesis and degradation of ceramide including serine palmitoyltransferase, sphingosine kinase 1, neutral sphingomyelinase, and ceramidases was markedly higher in the myocardium of OWT and T2D-OWT patients compared with lean subjects. Our results indicate that in the human heart, or at least in the atrium, ceramide is not a major factor in cardiomyocyte apoptosis associated with obesity and type 2 diabetes.

Serum adiponectin and markers of endothelial dysfunction in stable angina pectoris patients undergoing coronary artery bypass grafting (CABG)

PURPOSE It has been established that endothelial dysfunction (ED) occurs after coronary artery bypass grafting (CABG). The aim of the study was to assess whether adiponectin may act as a novel marker of ED and its potential relations with new markers of ED: novel cell adhesion molecule CD146, a natural anti-thrombin glycoprotein - thrombomodulin (TM) and the well-established ED marker - Von Willebrand factor (VWF) in coronary artery disease (CAD) patients undergoing CABG. MATERIAL/METHODS 45 CAD patients undergoing elective CABG were included in the study. RESULTS In the study group the concentration of adiponectin and CD146 before the surgery were significantly lower than in the control group - 6.06 μg/ml ± 3.06 vs. 19.0 μg/ml ± 6.4 and 303.2 ng/ml ± 28.7 vs. 328.1 ng/ml ± 22.6 (p<0.05). Significant increase of adiponectin and CD146 concentration 3 months after CABG vs. before the surgery was found. Adiponectin concentration 3 months after CABG correlated with VWF, TM, CD146, and a number of grafts. CD146 before and 3 months after CABG correlated significantly with adiponectin, VWF activity as well as the statins therapy after the surgery. CONCLUSIONS In CAD patients undergoing CABG new markers of endothelial cell dysfunction as adiponectin and CD146 are significantly lower compared to healthy volunteers. Significant increase in adiponectin and CD146 concentration 3 months after CABG vs. before the surgery was found. However adiponectin concentrations 3 months after CABG were still significantly lower compared to healthy individuals, whereas CD146 concentration returned to the values comparable to the control.

Impact of diabetes on mortality and complications after coronary artery by-pass graft operation in patients with left main coronary artery disease

PURPOSE Left main disease (LMD) is a severe form of coronary artery disease (CAD). Fifty percent of patients with LMD treated conservatively die within 3-5 years of diagnosis. The aim of the study was to assess the influence of type 2 diabetes on early and late (2-year) prognosis and the risk of complications after coronary artery by-pass graft (CABG) surgery in patients with LMD. MATERIAL/METHODS We enrolled 257 patients diagnosed with LMD. 169 (67%) underwent CABG, 19 (8%) percutaneous coronary intervention (PCI) without left main stem protection. 30 (12%) patients had CABG previously. Patients treated with CABG were divided into two groups - with and without diabetes. There were 43 (25.4%) patients with diabetes and 126 (74.6%) without diabetes. RESULTS We observed more complications with wound healing (40.5% vs. 12.8%, p<0.001) and sternal dehiscence (23.8% vs. 4.0%, p<0.001) after CABG in patients with diabetes. There were no differences in 7-day, 30-day, 3-month and 1-year mortality. 2-Year mortality was also similar in both groups (11.6% vs. 11.1%, p=0.928). Patients with diabetes were more frequently hospitalized due to other reasons than angina (39.5% vs. 20.6%, p=0.014). CONCLUSIONS Patients with diabetes and LMD had more often complications with wound healing and sternal dehiscence after CABG than patients without diabetes. Type 2 diabetes did not influence early and late mortality in patients with LMD treated with cardiac surgery, but the presence of diabetes was associated with more frequent hospitalizations.

Thrombocytopenia and perioperative complications after stentless Freedom Solo valve implantation.

BACKGROUND Freedom Solo (FS) stentless bioprostheses have superior haemodynamic performance compared to stented valves; however, the data of thrombocytopenia after FS implantations is disturbing. AIM To compare platelet count and perioperative complications between stentless and stented biological valves in patients undergoing aortic valve replacement. METHODS In 29 patients, FS bovine valves (Sorin Group, Saluggia, Italy) were implanted. Platelet counts were analysed before surgery, on the day of operation, on four consecutive postoperative days (POD) as well as at discharge, and compared to 29 control patients with biological stented porcine valves (Labcor Laboratorios TLBP-A Supra). The analysis of the perioperative variables extracorporeal circulation (ECC), aortic cross clamping (XC) and mechanical ventilation times, as well as blood supply, was performed. RESULTS Initial platelet counts were comparable in both groups. In the FS group, platelet levels on the four consecutive POD were significantly lower. The lowest platelet value (13 × 10³/μL), related to fatal thrombotic thrombocytopenic purpura, was found in one patient from the FS group. ECC as well as XC and mechanical ventilation times, were significantly longer in the FS group, and more blood transfusions in these patients were required. In multiple regression analysis, ECC and XC times did not correlate with platelet count. CONCLUSIONS Implantations of FS stentless bioprostheses are related to significantly lower platelet counts. Severe perioperative complications and their relation to thrombocytopenia need further evaluation.

The causes of thrombocytopenia after transcatheter aortic valve implantation

INTRODUCTION Even though thrombocytopenia following transcatheter aortic valve implantation (TAVI) has been described, further investigation of this phenomenon is needed. AIMS To determine which factors may explain the fall in platelet count that occurs after implantation of a TAVI device, including markers of platelet and blood coagulation activation. MATERIAL AND METHODS 32 patients without previous indications for dual antiplatelet therapy (mean age 78.5±7.9 years, 62% females) with severe aortic valve stenosis (mean gradient 54.6±16.9mmHg) who qualified for TAVI procedure (Edwards Sapien XT) were prospectively analyzed. Platelet counts were analyzed before the surgery, on the day of the procedure and for the three following postoperative days (POD 1 to 3). To assess platelet activation P-selectin (PS, serum) and platelet factor 4 (PF-4, CTAD plasma) were measured, whereas for the evaluation of coagulation activation prothrombin fragments 1+2 (F1+2, plasma) were assessed before the procedure, on POD-1 and POD-3 (ELISA). RESULTS During the postoperative period a significant platelet count drop, the most evident on POD-2, was observed followed by a platelet count raise. The platelet count drop correlated directly with the amount of iodinated contrast agent (r=0.42, p=0.016) and inversely with baseline mean platelet volume (r=-0.37, p=0.046). Neither clinical nor perioperative parameters, except contrast medium, influenced platelet count decrease. No significant differences regarding the concentration of the evaluated markers in patients with and without thrombocytopenia were found. PF-4 and F1+2 significantly changed during the study (p<0.05). Greater acute PF-4 decrease correlated with greater acute platelet count drop (r=0.48, p=0.043), and during the study slower PF-4 increase correlated with higher platelet count increase on POD-3 (r=-0.505, p=0.032). Lower baseline PS correlated with lower baseline platelet count and higher platelet count increase on POD-3 (r=0.45, p=0.04 and =-0.55, p=0.02, respectively). No significant correlations between F1+2 concentrations and platelet count changes have been found. CONCLUSIONS Platelet reduction shortly after TAVI procedure is related to the amount of contrast agent applied during the procedure. Platelet activation and blood coagulation along with impaired baseline platelet renewal might be the mechanisms of thrombocytopenia following TAVI procedure.

Thrombocytopenia associated with TAVI—The summary of possible causes

Thrombocytopenia (TP) following transcatheter aortic valve implantation (TAVI) procedure is a common phenomenon but the underlying mechanisms are neither well known nor described. Postinterventional severe TP is related to worse early and late outcome. Moreover, the statement of enhanced platelet and coagulation activation might justify even stronger antiplatelet and anticoagulation therapy following TAVI procedure. Thus, the examination of the pathomechanisms responsible for TP post TAVI seems to be crucial. Several hypotheses have been raised. TP can be caused by insufficient production or impaired platelet renewal. On the other hand, increased platelet activation, consumption and destruction might also be responsible for TP. These findings, mostly related to the procedure alone, need further investigation. Here, we summarize the potential multifactorial causes of post TAVI thrombocytopenia.

Atrial expression of the CCN1 and CCN2 proteins in chronic heart failure

Previous studies have reported the upregulation of CCN proteins early after acute heart injury. The aim of the present work was to evaluate the expression of the CCN1 and CCN2 proteins and their regulation by angiotensin II in the atrial myocardium of a chronically failing heart. Male adult mice were subjected to ligation of the left coronary artery to produce myocardial infarction (the MI group), and 16 of them were treated for 12 weeks with the AT1 receptor antagonist telmisartan (the MI-Tel group). Sham-operated mice served as controls. The expression of proteins was evaluated by immunohistochemistry 12 weeks after the operation. In shamoperated mice, stainings for CCN1 and CCN2 proteins were positive within atrial cardiomyocytes. CCN1-positive reaction revealed diffused cytoplasmic localization, while CCN2 was present mainly within the perinuclear cytoplasm. CCN1 was upregulated in the MI group, while CCN2 remained at basal level. Telmisartan prevented the upregulation of CCN1 and decreased CCN2 level. We compared the experimental data with the expression of CCN1 and CCN2 proteins in human right atrial appendages. We found an inverse, but not significant, relation between the level of either protein and the left ventricular ejection fraction. This suggests a similar atrial regulation of CCN1 and CCN2 expression also in humans. We conclude that in the murine atria, CCN1 and CCN2 proteins are expressed constitutively. In chronic heart failure, CCN proteins tend to be upregulated, which may be related to the action of angiotensin II.

Survival after surgical ablation for atrial fibrillation in mitral valve surgery: Analysis from the Polish National Registry of Cardiac Surgery Procedures (KROK)

Objectives: Surgical ablation for atrial fibrillation (AF) performed at the time of other valvular‐ or nonvalvular cardiac procedure is a mainstay of therapy; yet the data regarding its influence on remote survival are sparse. We aimed to evaluate late survival in patients undergoing mitral valve (MV) surgery with concomitant surgical ablation for AF. Methods: Procedure‐related data from the Polish National Registry of Cardiac Surgery Procedures (Krajowy Rejestr Operacji Kardiochirurgicznych) were retrospectively collected. A total of 11,381 patients with baseline AF (46.6% men; mean age 65.6 ± 9.0 years) undergoing MV surgery between 2006 and 2017 in 37 reference centers across Poland and included in the registry were analyzed. Median follow‐up was 5 years (mean, 4.6 years; interquartile range, 1.9‐7.9 years). Cox proportional hazards models were used for computations. Propensity score matching for the comparison of MV + ablation versus MV alone was performed. Results: Of included patients, 2449 (21.5%) underwent surgical ablation for AF. Patients in this group were significantly younger (63.8 ± 8.7 years vs 66.1 ± 9.0 years; P < .001) and were at lower baseline surgical risk (EuroSCORE, 2.86 vs 3.69; P < .001). During the 12‐year study period, there was a significant survival benefit (hazard ratio, 0.71; 95% confidence interval, 0.63‐0.79; P < .001) for MV + ablation compared with MV alone. After rigorous propensity matching (logit model, 1784 pairs) surgical ablation was associated with nearly 20% improved survival (hazard ratio, 0.82; 95% confidence interval, 0.70‐0.96; P = .011). Benefit of surgical ablation was maintained in subgroup analyses, yet most benefit was appraised in low‐risk patients such as those with EuroSCORE of 2 to 5 or age < 50 years. Conclusions: Concomitant surgical ablation for AF in patients undergoing mitral valve procedures is safe, feasible, and significantly improves late survival.

Effect of on-pump versus off-pump coronary bypass surgery on cardiac function assessed by intraoperative transesophageal echocardiography.

PURPOSE To compare cardiac function assessed by intraoperative transesophageal echocardiography in patients undergoing cardiac revascularization with or without cardiopulmonary bypass. MATERIAL AND METHODS Forty-one patients scheduled for elective, isolated cardiac revascularization (21 on-pump and 20 off-pump) were prospectively analyzed. Patients were matched for demographic (age and gender), anthropometric (BMI), clinical (co-morbidities, EuroScore) and laboratory variables (blood counts, renal function, left ventricular function). Transesophageal echocardiography was performed after induction of anesthesia, protamine sulfate administration, and chest closure. Left ventricular wall motion score index, end-diastolic area, fractional area change, right ventricular area change and end-diastolic area were assessed. Troponin I and C-reactive protein concentrations were measured. RESULTS Regarding echocardiographic parameters of left and right ventricular function no significant differences between on-pump and off-pump groups at any point-of-time measurements were found. Troponin I and C-reactive protein were higher in on-pump as compared to off-pump group (p=0.001 and p=0.002; p=0.003 and p=0.001, respectively). CONCLUSIONS In elective patients scheduled for cardiac revascularization there were no difference in cardiac performance assessed by intraoperative echocardiography regardless of surgical method used.

Cardiac rupture in takotsubo cardiomyopathy treated surgically

A 74-year-old woman, without a history of cardiological problems or risk factors of cardiovascular diseases, was admitted to the emergency room of our hospital after 2 h of chest pain. During the transport, the patient received 5000 U of unfractionated heparin, aspirin (300 mg) and clopidogrel (600 mg). The patient had suffered from an anxiety syndrome for several years. At admission, the patient was in a serious condition generally, was vomiting, and had severe chest pain with signs of cardiogenic shock (skin pale and wet, blood presure (BP) and heart rate (HR) undetectable). Electrocardiogram demonstrated a sinus rhythm of 58 per minute with QS complex and ST segment elevation in precordial leads (V2–V6). Laboratory results revealed increased troponin I concentration (2.041 ng/ml). Following hemodynamic stabilization, the patient was transported to the catheterization laboratory. Coronarography did not reveal any significant stenosis. Left ventricle angiography (LVA) showed normal volume with contractile disturbances of apex and hyperkinesis of the basement segments, with ejection fraction (EF) of 56%. Contrast outflow to the epicardium was observed within the area of the apex, through the perforated wall of the left ventricle (Figures 1 A–C). Echo confirmed the presence of fluid in the pericardium and cardiac tamponade. The patient was supported with intra-aortic balloon contra-pulsation and transported to the cardiac surgery for urgent intervention. During transport, the patient lost consciousness. After urgent cardiac tamponade decompression, the pulse and arterial pressure increased. Active bleeding through the ruptured left ventricle was observed in the area of the apex during the operation. Left ventricular plication with sutures on a double layered Teflon pad was performed. The lines of the sutures were conducted through healthy tissues. Examination of the supported ruptured region showed left ventricle tightness and complete hemostasis. No significant complications were observed during the perioperative period. On the first day after the operation the patient was extubated, and on the fifth day the intra-aortic balloon contra-pulsation was removed. The patient was transported to the regional hospital on day 11 to continue the therapeutic and rehabilitation procedures. A discharge echocardiogram revealed akinesis of the apex and hypokinesis of the septum, with an EF of 50%. The patient was under cardiosurgical follow-up for the next 3 months. She was in good general condition without any chest pain, and the wounds from the sternotomy were healing properly. In a 2.5-year long study the patient was in good condition and the echocardiogram conformed normokinesis of the left ventricle apex. She has been treated with bisoprolol 5 mg and aspirin 75 mg since hospitalization. Figure 1 A – ventriculography (left ventricular systole – normal volume of the left ventricle, contractile disturbances of the apex and hyperkinesis of the basement segments), B – ventriculography (left ventricular diastole), C – ... Most cases of takotsubo cardiomyopathy (TTC) have a good prognosis. However, occasionally the clinical outcome is complicated by cardiogenic shock, serious ventricular rhythm abnormalities or even cardiac rupture [1–3]. The mechanism of cardiac rupture in TTC is not as well understood as the causes of mechanical complications in other cases without significant coronary artery stenosis, i.e. dissolving thrombus, embolization, vessel spasm and myocardial bridging [4]. According to Kumar et al. [1] the risk factors for cardiac rupture in takotsubo patients are female gender, older age, persistent ST elevation, ST elevations in inferior leads (especially in II), higher systolic blood pressure and diastolic blood pressure, low EF and LV peak systolic pressure. The present case provides evidence of the significance of monitoring patients during the first days of the TTC syndrome. Only immediate diagnosis and urgent cardiosurgical intervention leads to a favorable prognosis in patients with TTC cardiomyopathy complicated by cardiac rupture.