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.

Background: The novel Navitor intra-annular self-expandable transcatheter aortic valve prosthesis is designed to improve coronary access, reduce paravalvular leaks, and enhance hemodynamic performance. Comparative data with the established Evolut platform (R, Pro, FX) are still lacking. This study aimed to evaluate the short-term clinical outcomes of Navitor (NAV) versus Evolut transcatheter heart valves. Methods: We conducted a single-center analysis of patients undergoing transfemoral TAVR between January 2015 and May 2024. A propensity score matching protocol including 18 baseline variables was used to balance baseline characteristics. Clinical outcomes were assessed using VARC-3 criteria. Results: Of 1067 TAVR patients, 210 were analyzed after matching—70 with the Nav valve and 140 with the Evolut valve. Baseline characteristics were comparable between groups, with a mean age of 80.9 ± 6.5 years in the NAV group and 80.7 ± 6.7 years in the Evolut group (p = 0.9). Both groups had an intermediate STS predicted risk of mortality, 3.9 ± 3.4% for NAV and 3.9 ± 3.2% for Evolut (p = 1.0). The effective aortic annulus diameter was comparable between the NAV (23.9 ± 1.5 mm) and Evolut group (23.9 ± 2.4 mm, p = 0.8). Hemodynamic performance at discharge was similar, with mean gradients of 7.5 ± 2.8 mmHg (NAV) vs. 7.4 ± 3.7 mmHg (Evolut, p = 0.9). Valve orifice areas and paravalvular leak rates showed no difference between the groups. Device success rates at discharge were good for both THVs: 89.3% for Evolut and 91.4% for NAV (p = 0.8). Disabling stroke occurred less frequently in the NAV group (0.0% vs. 7.1%, p = 0.033), while other early safety outcomes and 30-day mortalities were similar. Conclusions: The Navitor valve offers comparable hemodynamic performance, paravalvular leak rates, and procedural success to the Evolut platform. While early safety outcomes were largely similar, the Navitor valve was associated with a lower 30-day disabling stroke rate.

Background: Infective endocarditis (IE) after transcatheter aortic valve replacement (TAVR) is a severe complication. Surgical explantation of infected transcatheter heart valves (THV) is technically demanding and associated with high mortality. Data on risk factors for perioperative death and long-term outcomes remain limited. Aim: To identify predictors of mortality in patients undergoing surgical aortic valve replacement (SAVR) for IE after TAVR. Methods: We conducted a case–control study of patients treated with SAVR for IE after TAVR at our center between February 2008 and December 2023. Fifteen patients who died in hospital (cases) were compared with 35 perioperative survivors (controls). Hospital survivors were followed for long-term outcomes. Results: Age, sex, comorbidities (kidney disease, cerebrovascular disease, COPD, diabetes, peripheral artery disease), and anthropometrics were similar between groups. Cases had significantly lower left ventricular function and higher logistic EuroSCORE and STS-PROM before surgery. Causative microorganisms, cross-clamp time, and concomitant procedures did not differ. Postoperative pacemaker implantation, rethoracotomy, stroke, and ICU or hospital stay were comparable, while dialysis was more frequent in cases (44% vs. 25.7%). Median follow-up was 294 days (range 1–3802). Survival was 79.8% at 30 days and 67.4% at 1 year. Of 35 hospital survivors, 29 were discharged home, 6 to rehabilitation/other hospitals; 31 remain alive (1 early, 3 late deaths). Conclusions: SAVR for IE after TAVR carries high early mortality (18.1% at 30 days; 32.6% at 1 year). Higher preoperative risk scores and postoperative dialysis were associated with perioperative death. Long-term survival among hospital survivors is favorable, with most patients regaining independent living.

Background: Acute Stanford Type A aortic dissection (ATAAD) is a devastating disease requiring immediate surgery. A life-threatening complication hereby represents organ malperfusion. Lactate is a product of anaerobic glycolysis indicating organ malperfusion. The current study analyzes preoperative lactate acidosis as a surrogate marker for patients’ outcome after surgery for ATAAD over a 15-year period. Methods: In a single-center setting, 306 consecutive patients, who underwent surgery for ATAAD between 2000 and 2016, were analyzed retrospectively. Serum lactate measurements were taken before surgery. To define a simple cut-point of the predictor lactate, the maximally selected rank statistics method was used. Results: Median survival was 9.3 ± 0.5 and CI 95% [8.3–10.2] years. Mean lactate levels were 1.95 mmol/L ± 2.19 mmol/L (range: 0.15–19.27 mmol/L). Patients with a lactate level > 3.71 mmol/L had a higher 30-day mortality compared to patients with lactate levels ≤ 3.71 mmol/L (51.5% versus 18.7%). In a logistic regression model adjusted for clinical baseline characteristics at index procedure, lactate levels > 3.71 mmol/L reached the highest Odd for 30-day mortality of all tested risk factors (OR = 7.292; CI95% [3.029–17.555]; p < 0.0001). Analyzing the overall mortality, the early effect of lactate level > 3.71 mmol/L persists. The HRs for overall mortality, however, revealed substantially lower effects (HR = 2.772; (CI95% [1.689–4.550]; p < 0.0001). In patients who survived the first 30 days postoperatively, no clinical parameter other than age had a significant impact on survival, including lactate > 3.71 mmol/L (p = 0.494). Conclusions: In patients with ATAAD, preoperative lactate represents an easily obtainable surrogate marker for organ malperfusion. A preoperative lactate level > 3.71 mmol/L depicts the strongest marker for early mortality after surgery.

Background/Objectives: In the presence of porcelain aorta (PA), transcatheter aortic valve replacement (TAVR) has become a class I therapeutic indication for the treatment of severe aortic valve stenosis. To date, few studies have analyzed the clinical outcomes of TAVR in PA patients. We aim to analyze the calcification patterns of the thoracic aorta in PA patients and to evaluate their clinical implications for TAVR procedures. Methods: This study included 161 patients who had PA confirmed through pre-operative CT and underwent TAVR between 11/2014 and 12/2022. The primary outcome was to perform a multi-slice CT (MSCT) analysis assessing the calcification in the proximal, middle, and distal thoracic aortic segments. Each segment was divided into quadrants for scoring calcifications on a scale from 1 (75%). The cohort was categorized into circular or noncircular calcification group. The secondary clinical outcomes were defined according to VARC-3 criteria. Results: The study cohort included 161 patients (median age, 77.2 years; IQR, 70.1–82.6 years). The median EuroSCORE II and STS predicted risk of mortality were 3.10% [1.80–5.58] and 2.70% [1.70–4.30], respectively. In 75% of patients (n = 121/161), TAVR was performed via transfemoral access. Circular calcifications were found in 8.1% of patients, while noncircular calcifications were present in 91.9%. Significant calcifications were primarily in the right quadrant of the proximal segment (33.54%), superior quadrant of the middle segment (39.75%), and left quadrant of the distal segment (73.29%). The 30-day mortality rate was 3.11% and periprocedural ischemic stroke rate 3.38%. Conclusions: Most TAVR patients with PA exhibited noncircular calcification. The most extensive calcifications were primarily in areas relevant to surgical manipulation. Patients with PA displayed low short-term mortality and relatively few stroke events. In view of these findings, TAVR constitutes a valid treatment option for patients with PA and aortic stenosis.