Krzysztof Matlak

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.

Gene expression profiling reveals potential prognostic biomarkers associated with the progression of heart failure

BackgroundHeart failure (HF) is the most common cause of morbidity and mortality in developed countries. Here, we identify biologically relevant transcripts that are significantly altered in the early phase of myocardial infarction and are associated with the development of post-myocardial infarction HF.MethodsWe collected peripheral blood samples from patients with ST-segment elevation myocardial infarction (STEMI): n = 111 and n = 41 patients from the study and validation groups, respectively. Control groups comprised patients with a stable coronary artery disease and without a history of myocardial infarction. Based on plasma NT-proBNP level and left ventricular ejection fraction parameters the STEMI patients were divided into HF and non-HF groups. Microarrays were used to analyze mRNA levels in peripheral blood mononuclear cells (PBMCs) isolated from the study group at four time points and control group. Microarray results were validated by RT-qPCR using whole blood RNA from the validation group.ResultsSamples from the first three time points (admission, discharge, and 1 month after AMI) were compared with the samples from the same patients collected 6 months after AMI (stable phase) and with the control group. The greatest differences in transcriptional profiles were observed on admission and they gradually stabilized during the follow-up. We have also identified a set of genes the expression of which on the first day of STEMI differed significantly between patients who developed HF after 6 months of observation and those who did not. RNASE1, FMN1, and JDP2 were selected for further analysis and their early up-regulation was confirmed in HF patients from both the study and validation groups. Significant correlations were found between expression levels of these biomarkers and clinical parameters. The receiver operating characteristic (ROC) curves indicated a good prognostic value of the genes chosen.ConclusionsThis study demonstrates an altered gene expression profile in PBMCs during acute myocardial infarction and through the follow-up. The identified gene expression changes at the early phase of STEMI that differentiated the patients who developed HF from those who did not could serve as a convenient tool contributing to the prognosis of heart failure.

miR-22-5p revealed as a potential biomarker involved in the acute phase of myocardial infarction via profiling of circulating microRNAs

Acute myocardial infarction (AMI) is a life-threatening episode of coronary artery disease. Recently, circulating myocardial-derived microRNAs (miRNAs) have been reported as potential biomarkers of infarction. The present study aimed to identify differentially expressed miRNAs in patients with ST-segment elevation myocardial infarction that could be potentially dysregulated in response to early myocardial damage. miRNA expression profile analysis was performed using the Serum/Plasma Focus miRNA Polymerase Chain Reaction (PCR) panel of Exiqon A/S (Vedbaek, Denmark) on plasma samples of patients on the first day of AMI (admission) and on samples from the identical patients collected six months following AMI. Selected miRNAs were validated by reverse transcription‑quantitative PCR (RT‑qPCR) using independent patients with AMI and a control group of patients with a stable coronary artery disease. Thirty‑two species of plasma miRNA were differentially expressed (P<0.05) on admission compared with six months following AMI. Subsequent validation in an independent patient group confirmed that miR‑133b and miR‑22‑5p were significantly up‑regulated in the serum of patients with AMI. The receiver operating characteristic (ROC) curve analysis demonstrated a diagnostic utility for miR-22-5p, which has not previously been reported to be associated with AMI. Among the selected miRNAs, miR‑22‑5p represents a novel promising biomarker for the diagnosis of AMI.

Circulating miR-30a-5p as a prognostic biomarker of left ventricular dysfunction after acute myocardial infarction

Left ventricular (LV) dysfunction after acute myocardial infarction (AMI) is associated with an increased risk of heart failure (HF) development. Diverse microRNAs (miRNAs) have been shown to appear in the bloodstream following various cardiovascular events. The aim of this study was to identify prognostic miRNAs associated with LV dysfunction following AMI. Patients were divided into subgroups comprising patients who developed or not LV dysfunction within six months of the infarction. miRNA profiles were determined in plasma and serum samples of the patients on the first day of AMI. Levels of 14 plasma miRNAs and 16 serum miRNAs were significantly different in samples from AMI patients who later developed LV dysfunction compared to those who did not. Two miRNAs were up-regulated in both types of material. Validation in an independent group of patients, using droplet digital PCR (ddPCR) confirmed that miR-30a-5p was significantly elevated on admission in those patients who developed LV dysfunction and HF symptoms six months after AMI. A bioinformatics analysis indicated that miR-30a-5p may regulate genes involved in cardiovascular pathogenesis. This study demonstrates, for the first time, a prognostic value of circulating miR-30a-5p and its association with LV dysfunction and symptoms of HF after AMI.

Single-centre experience in surgery of acute aortic type A dissection and true aortic arch aneurysm.

BACKGROUND Surgery of the aortic arch is challenging. AIM To assess the results of aortic arch surgery. METHODS Analysis of 172 patients operated on arch dissection (emergency group: 97 patients) or aneurysm (elective group: 75 patients) between 2007 and 2014. Arch surgery was defined as a procedure requiring circumferential anastomosis at the level of the aortic arch or the descending aorta with the use of techniques of brain protection (deep hypothermic circulatory arrest [DHCA] or selective antegrade cerebral perfusion [SACP]) and/or debranching of at least one supra-aortic vessel. RESULTS Men predominated in both groups (> 70%). Men were younger in the emergency group (55 vs. 66 years; p < 0.008). The operative risk was higher in the emergency group (19.2% vs. 12.5%; p < 0.001). Forty-nine per cent of the patients from the emergency group and 5% from the elective group were operated with antiplatelet therapy (p < 0.001). Extended hemiarch procedure was performed in 79% (n = 77) in the emergency and 76% (n = 57) in the elective group. Total arch replacement was performed in 19 (21%) patients from the emergency and 18 (24%) patients from the elective group. In these patients debranching was performed in 68% of the emergency patients group and in 67% of the elective group. Elephant trunk procedure (classic/frozen) was performed in 53% (n = 10) from the emergency and in 78% (n = 14) of patients from the elective group. Aortic valve sparing surgery was performed in 20% of patients from the emergency and 9% from the elective group (p = 0.063). DHCA was performed in 58% (n = 43) of patients from the elective group and 39% (n = 37) from the emergency group. SACP was performed in 61% (n = 58) of patients from the emergency and 42% (n = 31) from the elective group. Thirty-day mortality in the emergency group reached 33% (n = 32), and in the elective group 15% (n = 11; p = 0.007). In multivariate analysis, predictors of death in the emergency group were: Logistic EuroSCORE above 19.5%, extracorporeal circulation time above 228 min, and postoperative acute renal failure (ARF); and in the elective group: DHCA time above 26 min, rethoracotomy due to bleeding, and ARF. Follow-up was completed in 100% of patients in terms of vital status. The mean follow-up time of the patients from the emergency group was 24.3 ± 27.10 (min 0, max 92) months, and from the elective group 30.3 ± 24.5 (min 0, max 99) months. During the follow-up period all-cause mortality in the emergency group was 43% (n = 42/97), and in the elective group it was 36% (n = 27/75). CONCLUSIONS Early mortality in the emergency group was higher, while long-term mortality did not differ among the groups. Postoperative ARF is a critical predictor of mortality in both groups.

Large intra-atrial structure 6 years after percutaneous atrial septal defect closure

A 52-year-old woman after percutaneous secundum atrial septal defect (ASD) closure (Occlutech Figulla ASD device 24 mm) 6 years ago was admitted with dyspnoea (NYHA Class II) and unspecific chest pain. Physical examination, electrocardiogram, and laboratory tests were normal. Transthoracic echocardiography revealed moving structure (46 × 21 mm) in left atrium, slightly flopping into left …

Hybrid thoracoabdominal procedure for acute aortic dissection Stanford type A using the EVITA OPEN PLUS – case report

Rozwarstwienie aorty typu A wg Stanford to stan zagrożenia życia wymagający pilnej interwencji kardiochirurgicznej. Obecnie obok klasycznych metod operacyjnych możliwe jest zastosowanie technik endowaskularnych. Przedmiotem niniejszego artykułu jest prezentacja przypadku 58-letniej chorej leczonej wieloetapowo z powodu rozwarstwienia aorty typu A wg Stanford, z wykorzystaniem technik hybrydowych, u której zakres leczenia objął całą aortę od zastawki aortalnej, z jej wymianą, do tętnic biodrowych. Słowa kluczowe: rozwarstwienie aorty typu A, operacja hybrydowa. Abstract