A riddle yet unsolved: two case reports of primary cardiac sarcoma.

Primary malignant cardiac tumors are exceedingly rare and dangerous, often leading to very early death after initial symptom presentation. Each case poses a unique challenge, as no standardized practice guidelines have been developed due to their sheer rarity. Surgical excision and adjuvant therapy remain the mainstays of treatment. However, resection is impeded by the unique challenges of cardiac surgery and growth characteristics of the tumors, both contributing to high rates of recurrence. We present two cases of successfully treated primary cardiac sarcoma with survival rates exceeding expectations.

Long Noncoding RNAs CARMN, LUCAT1, SMILR, and MALAT1 in Thoracic Aortic Aneurysm: Validation of Biomarkers in Clinical Samples.

MATERIALS AND METHODS: Relative expression of lncRNAs CARMN, LUCAT1, SMILR, and MALAT1 was tested in clinical aortic tissue and blood plasma samples from TAA and non-TAA patients using the qRT-PCR method. The Mann-Whitney U test was used to compare ΔCt values between the study groups. ROC curve analysis was performed to evaluate the diagnostic value of plasma lncRNAs. RESULTS: We found significantly reduced CARMN (p = 0.033) and LUCAT1 (p = 0.009) expression in aortic tissue samples from TAA patients. Relative expression of MALAT1 (p = 0.117) and SMILR (p = 0.610) did not differ in aortic tissue between the TAA and non-TAA groups. Expression of both LUCAT1 and SMILR was significantly decreased in TAA patients' blood plasma compared to controls (p = 0.018 and p = 0.032, respectively). However, only LUCAT1 showed the ability to discriminate aneurysmal disease in patients' blood plasma (AUC = 0.654, 95%CI = 0.534-0.775, p = 0.018). CONCLUSIONS: We have shown that the expression of lncRNAs CARMN and LUCAT1 is reduced in dilated aortic tissue and that the LUCAT1 and SMILR expression is lower in the blood plasma of TAA patients. Decreased LUCAT1 expression in TAA patients' blood plasma may have diagnostic potential in discriminating patients with TAA.

Predictors of early mortality after surgical treatment of infective endocarditis: a single-center experience.

OBJECTIVE: Surgical management of infective endocarditis continues to be challenging and is associated with significant morbidity and mortality. The objective of our study was to determine the risk factors and conditions associated with poor early infective endocarditis surgical treatment outcomes-30-day postoperative mortality. METHODS: A total of 124 patients who underwent surgery for infective endocarditis at the Hospital of Lithuanian University of Health Sciences Kaunas Clinics from January 2010 to December 2017 were retrospectively included in this study. The primary endpoints were 30-day postoperative mortality and identification of risk factors associated with it. Secondary endpoints were early postoperative outcomes and complication rates. RESULTS: During the study period, 124 patients with infective endocarditis underwent cardiac surgery, presenting an overall 30-day postoperative mortality rate of 10.48%. Mean age was 58 ± 14.4 years with 95 (76.61%) males. Independent predictive factors of early mortality were age >63 years (odds ratio = 6.4, 95% confidence interval = 1.66-24.66, p = 0.003), body mass index >30 kg/m² (odds ratio = 7.74, 95% confidence interval = 2.20-27.27, p = 0.003), and ischemic heart disease (odds ratio, 6.6, 95% confidence interval = 1.62-26.90, p = 0.003), as well as intraoperative parameters-prolonged aortic cross-clamp >84.5 minutes (odds ratio = 3.79, 95% confidence interval = 1.10-13.08, p = 0.03) and cardiopulmonary bypass time >107.5 minutes (odds ratio = 10.0, 95% confidence interval = 1.26-79.58, p = 0.023). Staphylococcus aureus infection (odds ratio = 5.04, 95% confidence interval = 1.29-19.64, p = 0.012), infective endocarditis-related intracardiac complication such as paravalvular abscess detected by transesophageal echocardiography (odds ratio = 4.32, 95% confidence interval = 1.31-14.25, p = 0.01), and infective endocarditis complicated by septic or cardiogenic shock (odds ratio, 18.43, 95% confidence interval = 4.59-73.98, p = 0.001) were statistically significant factors for increased risk of 30-day postoperative mortality. CONCLUSION: Surgical treatment of infective endocarditis showed good results in our center. The independent predictors of 30-day postoperative mortality for patients who underwent cardiac surgery for infective endocarditis were age, body mass index, ischemic heart disease, prolonged aortic cross-clamp and cardiopulmonary bypass time, Staphylococcus aureus infection, paravalvular abscess, and septic or cardiogenic shock.

Tissue-Specific miRNAs Regulate the Development of Thoracic Aortic Aneurysm: The Emerging Role of KLF4 Network.

MicroRNAs (miRNAs) are critical regulators of the functional pathways involved in the pathogenesis of cardiovascular diseases. Understanding of the disease-associated alterations in tissue and plasma will elucidate the roles of miRNA in modulation of gene expression throughout development of sporadic non-syndromic ascending thoracic aortic aneurysm (TAA). This will allow one to propose relevant biomarkers for diagnosis or new therapeutic targets for the treatment. The high-throughput sequencing revealed 20 and 17 TAA-specific miRNAs in tissue and plasma samples, respectively. qRT-PCR analysis in extended cohort revealed sex-related differences in miR-10a-5p, miR-126-3p, miR-155-5p and miR-148a-3p expression, which were the most significantly dysregulated in TAA tissues of male patients. Unexpectedly, the set of aneurysm-related miRNAs in TAA plasma did not resemble the tissue signature suggesting more complex organism response to the disease. Three of TAA-specific plasma miRNAs were found to be restored to normal level after aortic surgery, further signifying their relationship to the pathology. The panel of two plasma miRNAs, miR-122-3p, and miR-483-3p, could serve as a potential biomarker set (AUC = 0.84) for the ascending TAA. The miRNA-target enrichment analysis exposed TGF-ß signaling pathway as sturdily affected by abnormally expressed miRNAs in the TAA tissue. Nearly half of TAA-specific miRNAs potentially regulate a key component in TGF-ß signaling: TGF-ß receptors, SMADs and KLF4. Indeed, using immunohistochemistry analysis we detected increased KLF4 expression in 27% of TAA cells compared to 10% of non-TAA cells. In addition, qRT-PCR demonstrated a significant upregulation of ALK1 mRNA expression in TAA tissues. Overall, these observations indicate that the alterations in miRNA expression are sex-dependent and play an essential role in TAA via TGF-ß signaling.

Association between Fibrillin1 Polymorphisms (rs2118181, rs10519177) and Transforming Growth Factor ß1 Concentration in Human Plasma.

Transforming growth factor (TGF)-ß1 is a cytokine that participates in a broad range of cellular regulatory processes and is associated with various diseases including aortic aneurysm. Increased TGF-ß1 levels are linked to Marfan syndrome (MFS) caused by fibrillin1 (FBN1) mutations and subsequent defects in signaling system. FBN1 single nucleotide polymorphisms (SNPs) rs2118181 and rs1059177 do not cause MFS but are associated with dilative pathology of aortic aneurysms (DPAAs). TGF-ß1 and FBN1 SNPs rs2118181 and rs1059177 are potential biomarkers for early diagnosis of DPAA. We investigated the relationship between TGF-ß1 levels in human blood plasma and FBN1 rs2118181 and rs1059177 in 269 individuals. The results showed a quantitative dependence of SNP genotype and TGF-ß1 concentration. Presence of a single rs2118181 minor allele (G) increased the amount of TGF-ß1 by roughly 1 ng/mL. Two copies of FBN1 rs1059177 minor allele (G) were required to have an additive effect on TGF-ß1 levels. We found higher TGF-ß1 concentrations in men compared with women (p = 0.001). A strong correlation between TGF-ß1 levels and FBN1 SNPs suggests that a single nucleotide substitution in FBN1 sequence might reduce bioavailability or binding properties of fibrillin-1 and have an effect on TGF-ß1 activation and cytokine concentration in blood plasma. By establishing the relationship between TGF-ß1 and FBN1 SNPs rs2118181 and rs1059177, we provide evidence that their combination might be used as molecular biomarkers to identify patients at risk for sporadic ascending aortic aneurysm and aortic dissection.

Blood Plasma TGF- ß1 Concentration in Sporadic Dilatative Pathology of Ascending Aorta: More Questions than Answers.

Transforming growth factor ß1 (TGF- ß1) is a cytokine that participates in a broad range of cellular regulatory processes and is associated with various diseases including aortic aneurysm. Increased TGF- ß1 levels are associated with Marfan syndrome (MFS) caused by FBN1 mutations and subsequent defects in signaling system. We studied TGF- ß1 levels in 62 patients with sporadic, non syndromic, dilatative pathology of ascending aorta (DPAA) and in reference group subjects (n = 212). An initial screening of 212 reference individuals identified TGF- ß1 gender discrepancies and age-dependent cytokine increase in women. Patients with DPAA had increased levels of TGF- ß1 in comparison to reference group subjects (median 7.7 ng/ml, range 2.1-25.3, and median 6.2 ng/ml, range 1.0-33.1, respectively). There is a significant association between TGF-ß1 concentration and DPAA (OR 1.084, CI 1.027-1.144, p = 0.004) but the mechanisms of cause and effect have not been established yet. Slightly increased TGF-ß1 concentrations in patients with sporadic DPAA in comparison to the reference subjects show a potential use of TGF-ß1 as a biomarker for the disease. However, cytokine dependence on age, gender, and other unknown factors among individuals with no cardiovascular complains reduces its specificity for DPAA. We would also like to raise awareness regarding the choice of methods when measuring TGF-ß1 levels with an emphasis on preanalytical phase and the choice of sample.

FBN1 polymorphisms in patients with the dilatative pathology of the ascending thoracic aorta.

OBJECTIVES: To investigate polymorphisms of the fibrillin-1 (FBN1) gene (namely, rs2118181, rs1036477, rs10519177, rs755251 and rs4774517) in a case-control study for dilatative pathology of the ascending thoracic aorta (DPATA) from Lithuanians. METHODS: We studied 312 patients who had undergone aortic reconstructive surgery for DPATA. These patients were sub-divided according to the phenotypes of their DPATA into (i) ascending aortic aneurysm (n = 160), (ii) post-stenotic dilatation of the ascending aorta due to aortic valve stenosis (n = 79) and (iii) Stanford A dissection (n = 73). The reference group (n = 472) was recruited from a random sample screened within epidemiological studies of the Lithuanian population. FBN1 polymorphisms were studied by real-time polymerase-chain-reaction amplification. RESULTS: Patients within the aortic dissection sub-group had significantly higher minor allele frequencies in all five FBN1 single nucleotide polymorphism (SNPs) studied versus reference group subjects (P < 0.0001). Minor allele frequencies in SNPs rs2118181, rs1036477 were significantly higher in those with aortic aneurysm when compared with the reference group (P = 0.007). Thus, minor alleles of FBN1 SNPs studied were significantly associated with aortic dissection with odds ratios (ORs) 2.59-2.13, P < 0.001, while SNPs rs2118181 and rs1036477 with an increased risk of ascending aortic aneurysm [OR 1.67, confidence interval (CI) 95% 1.61-2.40]. The association of FBN1 genotypes with each phenotype of DPATA was assessed using logistic regression models adjusted for gender, age and hypertension. The additive model best fitted SNPs rs2118181 and rs1036477 in association with the ascending aortic aneurysm sub-group (OR 1.70, CI 95% 1.17-2.46) or the Stanford A dissection sub-group (OR 2.64, CI 95% 1.66-4.19). A recessive model fitted best the association between SNPs rs10519177, rs755251, rs4774517 and Stanford A dissection (OR 4.31, CI 95% 2.06-9.01). There were no significant associations between all studied FBN1 SNPs and post-stenotic or bicuspid aortic dilatation. CONCLUSIONS: Our study provides evidence for the following: (i) FBN1 SNPs rs2118181, rs1036477, rs10519177, rs4774517, rs755251 may increase susceptibility to aortic dissections and (ii) FBN1 SNPs rs2118181, rs1036477 to the formation of aortic aneurysms. Thus, these SNPs might be considered as biomarkers for identifying patients at risk for ascending aortic aneurysm and aortic dissection.