Felix Vogt

Background/Objectives: Percutaneous left atrial appendage occlusion (LAAO) has become an alternative to oral anticoagulation in selected patients with atrial fibrillation. The results of transcatheter LAAO were evaluated by conventional cardiac angiography (CCA), fluoroscopy, and 2D and 3D transesophageal echocardiography (TEE). Methods: In 47 consecutive patients (76 ± 8 years), LAAO was performed with the Amplatzer^TM device. CCA and 2D and 3D TEE were performed for LAA measurements. The eccentricity of the device landing zone was assessed by 3D TEE as the ratio of the maximal and minimal diameters. The device size was selected depending on the CCA maximal diameter. The postprocedural device lobe morphology was classified by fluoroscopy as “square” type (sign of undersizing), “tire” type (optimal deformation), and “strawberry” type (sign of oversizing). After 6 months, TEE was repeated to evaluate peri-device leaks (PDLs). Results: The postprocedural device morphology was “square” type in 9 (19%), “tire” type in 28 (60%), and “strawberry” type in 10 patients (21%). After 6 months, peri-device leaks were observed in 11 patients (23%), with the lowest incidence in the “tire”-type group (11%) compared with “square” type (56%) and “strawberry” type (30%) (p = 0.019). The 3D TEE eccentricity index with a cut-off value of ≤1.29 (indicating a more circular morphology) was a very specific predictor for excluding postprocedural device deformation of the “strawberry” type (AUC = 0.689; sensitivity 48.7%, specificity 100%). Conclusions: Undersizing as well as oversizing of the LAA occluder, as characterized by deformation type by fluoroscopy, was associated with postprocedural PDLs. The eccentricity of the LAA landing zone by 3D TEE may indicate inadequate size selection of the Amplatzer^TM device leading to oversizing in patients with a more eccentric LAA.

Objectives: We aimed to evaluate the efficacy and safety of low-dose protamine in reducing access site-related complications during Transcatheter Aortic Valve Implantation (TAVI) as compared to full-dose protamine. Background: Access site-related complications represent an independent predictor of poor outcomes of TAVI. Data regarding heparin reversal with protamine and the dosage needed to prevent bleeding complications are scarce among patients undergoing TAVI. Methods: A total of 897 patients were retrospectively included in the study. Patients who underwent percutaneous coronary intervention within 4 weeks before or concomitantly with TAVI (n = 191) were given 0.5 mg protamine for each 100 units of unfractionated heparin. All other patients (n = 706) were considered as a control group and 1 mg protamine for each 100 units of heparin was administered. Results: The combined intra-hospital endpoint of death, life-threatening major bleeding, and major vascular complications were significantly more frequent in patients receiving low-dose protamine [29 (15.2%) vs. 50 (7.1%), p < 0.001]. After propensity matching (n = 130 for each group) for relevant clinical characteristics including anti-platelet therapy [19 (14.6%) vs. 6 (4.6%), p = 0.006], low-dose protamine predicted the combined endpoint (OR 3.54, 95%-CI 1.36–9.17, p = 0.009), and even in multivariable analysis, low-dose protamine continued to be a predictor of the combined endpoint in the matched model (OR 3.07, 95%-CI 1.17–8.08, p = 0.023) alongside baseline hemoglobin. Conclusions: In this propensity-matched retrospective analysis, a low-dose protamine regime is associated with a higher rate of major adverse events compared to a full-dose protamine regime following transfemoral TAVI.

Extracellular collagen remodeling is one of the central mechanisms responsible for the structural and compositional coherence of myocardium in patients undergoing myocardial infarction (MI). Activated primary cardiac fibroblasts following myocardial infarction are extensively investigated to establish anti-fibrotic therapies to improve left ventricular remodeling. To systematically assess vitamin C functions as a potential modulator involved in collagen fibrillogenesis in an in vitro model mimicking heart tissue healing after MI. Mouse primary cardiac fibroblasts were isolated from wild-type C57BL/6 mice and cultured under normal and profibrotic (hypoxic + transforming growth factor beta 1) conditions on freshly prepared coatings mimicking extracellular matrix (ECM) remodeling during healing after an MI. At 10 μg/mL, vitamin C reprogramed the respiratory mitochondrial metabolism, which is effectively associated with a more increased accumulation of intracellular reactive oxygen species (iROS) than the number of those generated by mitochondrial reactive oxygen species (mROS). The mRNA/protein expression of subtypes I, III collagen, and fibroblasts differentiations markers were upregulated over time, particularly in the presence of vitamin C. The collagen substrate potentiated the modulator role of vitamin C in reinforcing the structure of types I and III collagen synthesis by reducing collagen V expression in a timely manner, which is important in the initiation of fibrillogenesis. Altogether, our study evidenced the synergistic function of vitamin C at an optimum dose on maintaining the equilibrium functionality of radical scavenger and gene transcription, which are important in the initial phases after healing after an MI, while modulating the synthesis of de novo collagen fibrils, which is important in the final stage of tissue healing.

Additive manufacturing (AM) is an emerging method for the fabrication of stents, which is cost-saving and capable of producing personalised stent designs. However, poor surface finish and dimension discrepancy in the manufactured stents can significantly affect not only their own mechanical behavior but also mechanical response of arteries. This study investigates the effects of surface irregularities and dimension discrepancy of a 316L stainless steel stent, manufactured using laser powder bed fusion (LPBF), on its biomechanical performance, in comparison with the original design and a commercial stent. In silico simulations of stent deployment in a patient-specific coronary artery, based on intravital optical coherency tomography imaging, are conducted to assess the stent deformation as well as arterial stress and damage. Severe plastic strain concentrations (with a maximum value of 1.93) occur in the LPBF stent after deployment due to surface irregularities, suggesting a high risk of stent fracture. The LPBF stent is harder to expand due to its thicker struts and closed-cell design (diameter of 4.14 mm at the peak inflating pressure during deployment, compared to 4.58 mm and 4.65 mm for the designed and MULTI-LINK RX ULTRA stents, respectively). Also, the LPBF stent induces a higher level of stress concentration (with a maximum value of 23.04 MPa) to the arterial layers, suggesting a higher risk of tissue damage and in-stent restenosis. This study demonstrates a clear need for further development of the AM process for manufacturing medical implants, especially the surface finish and dimension accuracy.

Background: Transcutaneous edge-to-edge repair (TEER) has become a treatment option for selected patients with severe mitral regurgitation (MR). Analysis of the COAPT trial indicated patients with diabetes mellitus to have higher death rates and a trend to higher rates of heart failure hospitalization (HFH) than those without diabetes. However, in that study only patients with secondary MR with specific criteria were included and there are only limited data on diabetes patients in real-world settings. Purpose: This study sought to evaluate safety and efficacy of TEER in patients with diabetes mellitus in comparison to non-diabetics. Methods: In this monocentric study 340 consecutive patients with severe primary and secondary MR who underwent TEER were included. Immediate results of the procedure, intrahospital as well as one-year outcome were compared between patients with and without diabetes. Results: Diabetes was present in 109 patients (32%) of the study group. Patients with diabetes were younger (75±8 vs. 78±8 years; p=0.003), had more often ischemic cardiomyopathy (68% vs. 48%, p<0.001), previous coronary-artery bypass graft (35% vs. 20%; p=0.002) and arterial hypertension (89% vs. 75%; p<0.001) compared to those without diabetes. All other baseline clinical and imaging characteristics including NYHA class, left ventricular dimensions and function (ejection fraction: 38±13% vs. 41±14%; p=0.10) as well as severity of MR were not different between both patient groups (Table 1). Success of the procedure was comparable between patients with and without diabetes (95% vs. 95%; p=0.84). There was no difference in intrahospital mortality between both groups (5.5% vs. 4.8%; p=0.98). At one-year follow up, there was no difference regarding all-cause mortality (24.2% vs. 23.0%; p=0.72), HFH (37.4% vs. 31.0%, p=0.23), NYHA class (p=0.11) or MR severity (p=0.20) between both groups (Table 2). Conclusion: In contrast to previous published data on patients with diabetes and severe MR TEER seems to be similar safe and effective in a real-world setting compared to non-diabetics. Funding Acknowledgement: Type of funding sources: None.

Background: By low-density lipoprotein (LDL) reduction, statins play an important role in cardiovascular risk modification. Incompletely understood pleiotropic statin effects include vasoprotection that might originate from mobilisation and differentiation of vascular progenitor cells. Data on the potentially differential impact of statin treatment intensity on circulating progenitor cells in patients undergoing percutaneous coronary intervention (PCI) are scarce. This study examines the potential association of different permanent statin treatment regimens on circulating progenitor cells in patients with coronary syndrome. Methods and results: In a monocentric prospective all-comers study, 105 consecutive cases scheduled for coronary angiography due to either (A) non-invasive proof of ischemia and chronic coronary syndrome (CCS) or (B) troponin-positive acute coronary syndrome (ACS) were included. According to the 2018 American College of Cardiology Guidelines on Blood Cholesterol, patients were clustered depending on their respective permanent statin treatment regimen in either a high- to moderate-intensity statin treatment (HIST) or a low-intensity statin treatment (LIST) group. Baseline characteristics including LDL levels were comparable. From blood drawn at the time of PCI, peripheral blood mononuclear cells were isolated, cultivated and counted and, by density gradient centrifugation, levels of circulating progenitor cells were determined using fluorescence-activated cell sorting (FACS) analysis. In ACS patients both absolute and relative numbers of circulating early-outgrowth endothelial progenitor cells (EPCs) concurrently were significantly lower in the HIST group as compared to the LIST group. This effect was more pronounced in ACS patients than in CCS patients. Both in ACS and CCS patients, HIST caused a significant reduction of the number of circulating SMPCs. Conclusions: In patients undergoing PCI, a dose intensity-dependent and LDL level-independent pro-differentiating vasoprotective pleiotropic capacity of statins for EPC and SMPC is demonstrated.

Coronary artery systems of the inferior wall of the ventricles vary considerably. Schlesinger's concept distinguishes dominance of the right or left coronary artery (LCA) or balanced type. LCA dominance has been reported to be associated with increased mortality. Early angiography studies have shown that the anterior interventricular artery (AIVA), a branch of the LCA, often continues on the inferior surface of the heart and may replace the inferior interventricular artery. Others considered an AIVA on the inferior surface of the heart a rare variant. A long AIVA is a strong predictor of death in acute anterior wall myocardial infarction. We determined coronary artery variance at the inferior surface of the ventricles in 134 dissected human hearts and analyzed a possible association between coronary artery variance and age at death. The AIVA extended to the inferior side in 64.9% of the hearts, but rarely reached the basal half of the inferior interventricular groove. Most frequently (53%), it extended into the apical two‐fifths of the length of the inferior ventricular walls. An AIVA extending to the apical 40% of the length of the inferior ventricular walls may therefore be considered a common variant. In 20.1% of the hearts, a right inferior diagonal artery was also found. Statistical analysis neither revealed an association between mean AIVA length at the inferior ventricular surface and type of coronary artery dominance nor an association between AIVA length at the inferior ventricular surface or coronary artery dominance type and age at death.