Aggrecan: a new biomarker for acute type A aortic dissection.

Acute type A aortic dissection (ATAAD) constitutes a life-threatening aortic pathology with significant morbidity and mortality. Without surgical intervention the usual mortality rate averages between 1 and 2% per hour. Thus, an early diagnosis of ATAAD is of pivotal importance to direct the affected patients to the appropriate treatment. Preceding tests to find an appropriate biomarker showed among others an increased aggrecan (ACAN) mRNA expression in aortic tissue of ATAAD patients. As a consequence, we investigated whether ACAN is a potential biomarker for diagnosing ATAAD. Mean ACAN protein concentration showed a significantly higher plasma concentration in ATAAD patients (38.59 ng/mL, n = 33) compared to plasma of patients with thoracic aortic aneurysms (4.45 ng/mL, n = 13), patients with myocardial infarction (11.77 ng/mL, n = 18) and healthy volunteers (8.05 ng/mL, n = 12). Cardiac enzymes like creatine kinase MB and cardiac troponin T showed no correlation with ACAN levels in ATAAD patients. Receiver-operator characteristics (ROC) curve analysis for ATAAD patients versus control subjects an optimum discrimination limit of ACAN plasma levels at 14.3 ng/mL with a corresponding sensitivity of 97% and specificity of 81%. According to our findings ACAN is a reliable potential biomarker in plasma samples to detect ATAAD with high sensitivity and specificity.

Congenital heart disease risk loci identified by genome-wide association study in European patients.

Genetic factors undoubtedly affect the development of congenital heart disease (CHD) but still remain ill defined. We sought to identify genetic risk factors associated with CHD and to accomplish a functional analysis of SNP-carrying genes. We performed a genome-wide association study (GWAS) of 4034 White patients with CHD and 8486 healthy controls. One SNP on chromosome 5q22.2 reached genome-wide significance across all CHD phenotypes and was also indicative for septal defects. One region on chromosome 20p12.1 pointing to the MACROD2 locus identified 4 highly significant SNPs in patients with transposition of the great arteries (TGA). Three highly significant risk variants on chromosome 17q21.32 within the GOSR2 locus were detected in patients with anomalies of thoracic arteries and veins (ATAV). Genetic variants associated with ATAV are suggested to influence the expression of WNT3, and the variant rs870142 related to septal defects is proposed to influence the expression of MSX1. We analyzed the expression of all 4 genes during cardiac differentiation of human and murine induced pluripotent stem cells in vitro and by single-cell RNA-Seq analyses of developing murine and human hearts. Our data show that MACROD2, GOSR2, WNT3, and MSX1 play an essential functional role in heart development at the embryonic and newborn stages.

Myosin binding protein H-like (MYBPHL): a promising biomarker to predict atrial damage.

Myosin binding protein H-like (MYBPHL) is a protein associated with myofilament structures in atrial tissue. The protein exists in two isoforms that share an identical amino acid sequence except for a deletion of 23 amino acids in isoform 2. In this study, MYBPHL was found to be expressed preferentially in atrial tissue. The expression of isoform 2 was almost exclusively restricted to the atria and barely detectable in the ventricle, arteria mammaria interna, and skeletal muscle. After atrial damage induced by cryo- or radiofrequency ablation, MYBPHL was rapidly and specifically released into the peripheral circulation in a time-dependent manner. The plasma MYBPHL concentration remained substantially elevated up to 24 hours after the arrival of patients at the intensive care unit. In addition, the recorded MYBPHL values were strongly correlated with those of the established biomarker CK-MB. In contrast, an increase in MYBPHL levels was not evident in patients undergoing aortic valve replacement or transcatheter aortic valve implantation. In these patients, the values remained virtually constant and never exceeded the concentration in the plasma of healthy controls. Our findings suggest that MYBPHL can be used as a precise and reliable biomarker to specifically predict atrial myocardial damage.

Sutureless Perceval aortic valve in comparison with the stented Carpentier-Edwards Perimount aortic valve.

BACKGROUND AND AIM OF THE STUDY: The Sorin Perceval S (SP) sutureless bioprosthesis was developed as an advancement of conventional biological aortic valve replacement (AVR) with stented bioprostheses, and perhaps also as an alternative to the transcatheter aortic valve implantation (TAVI) procedure, especially for high-risk patients. Herein are described the authors' early results with SP valve replacement, compared to AVR with Carpentier-Edwards Perimount (EP) stented valves. METHODS: Between September 2012 and February 2013, a total of 14 patients was enrolled in a single-center SP study group, and their data were analyzed in a prospective manner. For comparison, 14 patients who received an EP valve replacement during the same period were matched with the SP group, in a retrospective manner. Hemodynamic parameters and clinical outcome were monitored until discharge of the patients in order to analyze the early results of the two groups. RESULTS: The cardiopulmonary bypass (CPB) and aortic cross-clamp (ACC) times needed for AVR with SP valves were significantly shorter than with EP valves. The mean CPB time for SP valve replacement without concomitant procedures was 58.4 +/- 11.0 min, compared to 71.8 +/- 11.3 min in the EP group (p = 0.015), while the mean ACC times were 37.3 +/- 6.8 and 49.1 +/- 11.2 min, respectively (p = 0.006). Permanent pacemaker implantation was required in four patients after SP valve replacement, but in only one patient after EP valve replacement (p = 0.326). The mean transprosthetic peak and mean gradients were 24.8 +/- 5.2 mmHg and 13.3 +/- 3.3 mmHg, respectively, in the SP group, and 19.0 +/- 6.5 mmHg and 10.4 +/- 3.0 mmHg, respectively, in the EP group (p = 0.024 and p = 0.087). The mean valve size was 23.8 +/- 1.3 mm and 23.3 +/- 1.5 mm in the SP and EP groups, respectively. The fall in platelet count after SP valve replacement was 180.4 +/- 79.4 x 10(3)/microl on the first postoperative day (POD), and 114.1 +/- 51.2 x 10(3)/microl with a minimum of 42 x 10(3)/microl and a maximum of 230 x 10(3)/microl at the nadir on POD 2.6 +/- 4.0. The mean minimum values at the nadir corresponded to 40% of the initial preoperative value. CONCLUSION: The sutureless SP bioprosthesis seems to represent a good alternative to conventional stented bioprostheses, especially in older patients with a high-risk profile, and particularly if concomitant surgical procedures are planned.