Outcomes of transfemoral TAVR using two new-generation devices in patients with horizontal aorta.

BACKGROUND: Challenging anatomies and comorbidities have impact on success in transcatheter aortic valve replacement (TAVR). There is controversy whether the extent of the aortic angle (AA) has an impact on procedural outcomes. Matched comparative outcome data of new generation transcatheter heart valves (THVs) in horizontal aorta (HA) are scarce. METHODS: A total of 1582 patients with severe native aortic stenosis (AS) treated with the SAPIEN3 Ultra (Ultra; n = 526) or ACURATE Neo2 (Neo2; n = 1056) THVs from January 2017 to January 2023 were analyzed. Patients with non-horizontal aortas (AA < 51.7°, n = 841) were excluded. The population was matched by 1-to-1 nearest-neighbor matching (Ultra, n = 246; Neo2, n = 246). Clinical and procedural outcome were evaluated according to VARC-3 recommendations. RESULTS: Technical success (93.1% vs. 94.7%, p = 0.572) was high after Ultra and Neo2. Device success (80.5% vs. 89.8%, p = 0.05) was inferior with Ultra. Neo2 reveals superior hemodynamic properties with lower rate of severe prosthesis patient mismatch (12.0% vs. 3.7%, p = 0.001) and elevated gradients ( ≥ $\ge $ 20 mmHg: 11.9% vs. 1.7%, p < 0.001). Ultra showed a lower rate of relevant paravalvular regurgitation ( > $\gt $ mild paravalvular regurgitation or Valve-in-Valve due to paravalvular regurgitation: 0.0% vs. 3.7%, p = 0.004). The rate of procedural bailout maneuvers (0.8% vs. 0.4%, p = 1.000) and thirty-day all-cause mortality (1.3% vs. 2.2%, p = 0.496) was similar. CONCLUSION: Transfemoral TAVR in patients with severe aortic stenosis and HA, using the balloon expandable Sapien3 Ultra and self-expanding ACURATE Neo2 prosthesis, is feasible and safe. Therefore, valve selection between these platforms should be made irrespective of the aortic angle by a team experienced with both valves based on their specific advantages. Large, randomized trials in this sub-group of patients would be necessary to compare long term outcomes.

Impact of Diabetes in Patients With Acute Myocardial Infarction Undergoing Coronary Artery Bypass Surgery Within 48 Hours.

BACKGROUND: Diabetic patients with coronary artery disease may benefit from elective coronary artery bypass graft (CABG) surgery. It is unknown whether this merit is transferable to patients with acute myocardial infarction (AMI) undergoing surgery. METHOD: A total of 1,427 patients underwent CABG within 48 hours of being diagnosed with AMI at the current institution between 2001 and 2019. Of these patients, 206 (14.4%) had insulin-dependent diabetes mellitus (IDDM) and 148 (10.4%) had non-insulin dependent diabetes mellitus (NIDDM). Retrospective data analysis was performed. RESULTS: Patients with NIDDM showed the highest perioperative risk profile, with a EuroScore II of 11.6 (±10.3) compared with 7.8 (±8.0) in non-diabetic patients and 8.4 (±7.8) in patients with IDDM (p<0.001). Sub-analysis demonstrated a higher proportion of non-ST-elevation myocardial infarction patients in the NIDDM cohort compared with the IDDM cohort (70.9% vs 56.8%; p=0.005). Postoperatively, NIDDM patients had more sepsis (p<0.01) and longer ventilation times (p<0.001) compared with non-DM and IDDM patients (p<0.01). Wound healing complications were rare, but almost twice as high in NIDDM patients compared with non-DM and IDDM patients (4.7% vs 0.9% vs 2.4%, respectively). The 30-day mortality was highest in the NIDDM cohort (18.3% vs 11.3% vs 7.8%; p=0.012). Analysis of survival for up to 15 years revealed a significantly reduced survival of diabetic patients compared with non-diabetic patients, with lowest survival rates in NIDDM patients (p<0.001). CONCLUSIONS: Non-insulin dependent diabetes mellitus patients undergoing CABG within 48 hours of being diagnosed with AMI are at increased risk of short-term and long-term complications. Therefore, this particular group should undergo a careful evaluation concerning the expected risks and benefits of CABG in this setting.

Latest Advances in Transcatheter Aortic Valve Implantation (2022).

Since the last decade, transcatheter aortic valve implantation (TAVI) has become the treatment of choice in patients with symptomatic severe aortic stenosis (AS) who are ineligible or at higher risk for surgery. Due to the high safety profile of current device generation, TAVI has emerged as a qualified alternative to surgical aortic valve replacement (SAVR) in patients with classic aortic stenosis and intermediate surgical risk, severe bicuspid aortic valve stenosis, and isolated pure aortic regurgitation. Moderate aortic stenosis, with and without concomitant heart failure with reduced ejection fraction, are under investigation in randomized controlled clinical trials from which we will gain exciting insights on the best timing of TAVI to protect the left ventricle from further functional deterioration due to increasing AS. In these cases, a meticulous diagnostic approach including advanced imaging is becoming more and more important. Current evidence on antithrombotic strategies after TAVI is weak, contributing to poor levels of standardization and high variability in daily clinical practice. This review will provide a short overview of recent clinical trials including best timing for TAVI with moderate AS and antithrombotic strategies after TAVI with current and future TAVI generations.

Minimally Invasive Direct Coronary Artery Bypass in High-Risk Patients with Multivessel Disease.

BACKGROUND: High-risk patients with multivessel disease (MVD) including a complex stenosis of the left anterior descending coronary may not be ideal candidates for guideline compliant therapy by coronary artery bypass grafting (CABG) regarding invasiveness and perioperative complications. However, they may benefit from minimally invasive direct coronary artery bypass (MIDCAB) grafting and hybrid revascularization (HCR). METHODS: A logistic European system for cardiac operative risk evaluation score (logES) >10% defined high risk. In high-risk patients with MVD undergoing MIDCAB or HCR, the incidence of major adverse cardiac and cerebrovascular events (MACCEs) after 30 days and during midterm follow-up was evaluated. RESULTS: Out of 1,250 patients undergoing MIDCAB at our institution between 1998 and 2015, 78 patients (logES: 18.5%; age, 76.7 ± 8.6 years) met the inclusion criteria. During the first 30 days, mortality and rate of MACCE were 9.0%; early mortality was two-fold overestimated by logES. Complete revascularization as scheduled was finally achieved in 64 patients (82.1%). Median follow-up time reached 3.4 (1.2-6.5) years with a median survival time of 4.7 years. Survival after 1, 3, and 5 years was 77, 62, and 48%. CONCLUSION: In high-risk patients with MVD, MIDCAB is associated with acceptable early outcome which is better than predicted by logES. Taking the high-risk profile into consideration, midterm follow-up showed satisfying results, although scheduled HCR was not realized in a relevant proportion. In selected cases of MVD, MIDCAB presents an acceptable alternative for high-risk patients.

Randomized trial of ticagrelor vs. aspirin in patients after coronary artery bypass grafting: the TiCAB trial.

AIMS: The antiplatelet treatment strategy providing optimal balance between thrombotic and bleeding risks in patients undergoing coronary artery bypass grafting (CABG) is unclear. We prospectively compared the efficacy of ticagrelor and aspirin after CABG. METHODS AND RESULTS: We randomly assigned in double-blind fashion patients scheduled for CABG to either ticagrelor 90 mg twice daily or 100 mg aspirin (1:1) once daily. The primary outcome was the composite of cardiovascular death, myocardial infarction (MI), repeat revascularization, and stroke 12 months after CABG. The main safety endpoint was based on the Bleeding Academic Research Consortium classification, defined as BARC ≥4 for periprocedural and hospital stay-related bleedings and BARC ≥3 for post-discharge bleedings. The study was prematurely halted after recruitment of 1859 out of 3850 planned patients. Twelve months after CABG, the primary endpoint occurred in 86 out of 931 patients (9.7%) in the ticagrelor group and in 73 out of 928 patients (8.2%) in the aspirin group [hazard ratio 1.19; 95% confidence interval (CI) 0.87-1.62; P = 0.28]. All-cause mortality (ticagrelor 2.5% vs. aspirin 2.6%, hazard ratio 0.96, CI 0.53-1.72; P = 0.89), cardiovascular death (ticagrelor 1.2% vs. aspirin 1.4%, hazard ratio 0.85, CI 0.38-1.89; P = 0.68), MI (ticagrelor 2.1% vs. aspirin 3.4%, hazard ratio 0.63, CI 0.36-1.12, P = 0.12), and stroke (ticagrelor 3.1% vs. 2.6%, hazard ratio 1.21, CI 0.70-2.08; P = 0.49), showed no significant difference between the ticagrelor and aspirin group. The main safety endpoint was also not significantly different (ticagrelor 3.7% vs. aspirin 3.2%, hazard ratio 1.17, CI 0.71-1.92; P = 0.53). CONCLUSION: In this prematurely terminated and thus underpowered randomized trial of ticagrelor vs. aspirin in patients after CABG no significant differences in major cardiovascular events or major bleeding could be demonstrated. CLINICALTRIALS.GOV IDENTIFIER: NCT01755520.

Iatrogenic Catheter-Induced Acute Aortic Dissection Type A after Coronary Angiography-A Retrospective Consecutive Case Series.

Background Acute aortic dissection type A (AADA) is one of the most life-threatening situations and surgical demanding procedures even today. Usually AADA develops spontaneously, but it can be related also to interventional procedures. Methods We analyzed the data of 14 patients surgically treated in our institution with catheter-induced AADA (ciAADA) during coronary angiography between January 2004 and December 2014. Data were compared with overall AADA patients in this time period (n = 288). Results Nine of the 14 patients were female. Subjects were significantly older compared to the AADA patients (69 ± 11 vs. 62 ± 11; p = 0.021). At admission, ciAADA patients were more often hemodynamically instable and mechanically ventilated. Twelve patients underwent replacement of the ascending aorta and two patients received a modified Bentall operation. Cardiopulmonary bypass time (210 ± 92 vs. 172 ± 51 min) and cross-clamp time (122 ± 63 vs. 92 ± 40 min) were significantly longer due to additional coronary artery bypass grafts in 71.4 versus 3.1% due to myocardial ischemia. Operative mortality (7.1 vs. 2.1%, p = 0.29) and 30-day mortality (50.0 vs. 10.7%, p < 0.001) were higher in the ciAADA group. Conclusion Coronary angiography-induced AADA is a rare but severe complication. Due to additional myocardial ischemia and preoperative hemodynamic instability, patients with ciAADA have adverse outcome compared to overall AADA patients.

Toll-like receptor 2/6 agonist macrophage-activating lipopeptide-2 promotes reendothelialization and inhibits neointima formation after vascular injury.

OBJECTIVE: Reendothelialization after vascular injury (ie, balloon angioplasty or stent implantation) is clinically extremely relevant to promote vascular healing. We here investigated the therapeutic potential of the toll-like receptor 2/6 agonist macrophage-activating lipopeptide (MALP)-2 on reendothelialization and neointima formation in a murine model of vascular injury. APPROACH AND RESULTS: The left common carotid artery was electrically injured, and reendothelialization was quantified by Evans blue staining after 3 days. A single injection of MALP-2 (1 or 10 µg, IV) after vascular injury accelerated reendothelialization (P<0.001). Proliferation of endothelial cells at the wound margins determined by 5-ethynyl-2'-deoxyuridine incorporation was significantly higher in MALP-2-treated animals (P<0.05). Furthermore, wire injury-induced neointima formation of the left common carotid artery was completely prevented by a single injection of MALP-2 (10 µg, IV). In vitro, MALP-2 induced proliferation (BrdU incorporation) and closure of an artificial wound of endothelial cells (P<0.05) but not of smooth muscle cells. Protein array and ELISA analysis of isolated primary endothelial cells and ex vivo stimulated carotid segments revealed that MALP-2 stimulated the release of multiple growth factors and cytokines predominantly from endothelial cells. MALP-2 induced a strong activation of the mitogen-activated protein kinase cascade in endothelial cells, which was attenuated in smooth muscle cells. Furthermore, MALP-2 significantly enhanced circulating monocytes and hematopoietic progenitor cells. CONCLUSIONS: The toll-like receptor 2/6 agonist MALP-2 promotes reendothelialization and inhibits neointima formation after experimental vascular injury via enhanced proliferation and migration of endothelial cells. Thus, MALP-2 represents a novel therapeutic option to accelerate reendothelialization after vascular injury.

Case Report: The woman with the big heart-an imaging-guided attempt of surgical reduction.

In a female patient with acute cardiac decompensation, an auxiliary finding of a giant left atrium emerged. The surgical therapy of the atrial reduction, in addition to a mitral valve replacement and a coronary artery bypass grafting, is hereby presented.

ACURATE neo2 Versus SAPIEN 3 Ultra Transcatheter Heart Valve in Severe Aortic Valve Calcification: A Propensity-Matched Analysis.

BACKGROUND: Comparative data on transcatheter self-expanding ACURATE neo2 (NEO2) and balloon-expandable SAPIEN 3 Ultra prostheses in technically challenging anatomy of severe aortic valve calcified aortic annuli are scarce. METHODS: A total of 1987 patients with severe native aortic stenosis treated with the self-expanding NEO2 (n=1457) or balloon-expandable SAPIEN 3 Ultra (n=530) from January 2017 to April 2023 were evaluated. The primary end point was procedural outcome according to the Valve Academic Research Consortium 3 definitions. Propensity matching defined 219 pairs with severe calcification (calcium density cutoff, 758 AU/cm2) of the native aortic valve. RESULTS: Technical success (90.4% versus 91.8%; risk difference, 1.4% [95% CI, -4.4 to -7.2]; P=0.737) and device success at 30 days (80.8% versus 75.8%; risk difference, -5.0% [95% CI, -13.2 to 3.1]; P=0.246) were comparable between NEO2 and SAPIEN 3 Ultra. The rate of severe prosthesis-patient mismatch (1.1% versus 10.1%; risk difference, 10.0% [95% CI, 4.0-13.9]; P<0.001) and mean transvalvular gradient ≥20 mm Hg (2.8% versus 14.3%; risk difference, 11.5% [95% CI, 5.8-17.1]; P<0.001) was lower with NEO2. The rate of more-than-mild paravalvular leakage or valve-in-valve due to paravalvular leakage was significantly higher (6.2% versus 0.0%; risk difference, 6.2% [95% CI, -10.1 to -2.7]; P=0.002), and there was a tendency for a higher rate of device embolization or migration (1.8% versus 0.0%; risk difference, -1.8% [95% CI, -4.1 to 0.4]; P=0.123) with NEO2. Multivarate regression revealed no independent impact of transcatheter heart valve selection on device success (odds ratio, 0.93 [95% CI, 0.48-1.77]; P=0.817). CONCLUSIONS: In patients with severely calcified annuli, supraannular implantation of NEO2 showed hemodynamic advantages. Nevertheless, NEO2 was associated with a higher incidence of relevant paravalvular leakage and a numerically higher rate of device embolization than SAPIEN 3 Ultra in this particular patient group.

Signal transducer of inflammation gp130 modulates atherosclerosis in mice and man.

Liver-derived acute phase proteins (APPs) emerged as powerful predictors of cardiovascular disease and cardiovascular events, but their functional role in atherosclerosis remains enigmatic. We report that the gp130 receptor, which is a key component of the inflammatory signaling pathway within hepatocytes, influences the risk of atherosclerosis in a hepatocyte-specific gp130 knockout. Mice on an atherosclerosis-prone genetic background exhibit less aortic atherosclerosis (P < 0.05) with decreased plaque macrophages (P < 0.01). Translating these findings into humans, we show that genetic variation within the human gp130 homologue, interleukin 6 signal transducer (IL6ST), is significantly associated with coronary artery disease (CAD; P < 0.05). We further show a significant association of atherosclerotic disease at the ostium of the coronary arteries (P < 0.005) as a clinically important and heritable subphenotype in a large sample of families with myocardial infarction (MI) and a second independent population-based cohort. Our results reveal a central role of a hepatocyte-specific, gp130-dependent acute phase reaction for plaque development in a murine model of atherosclerosis, and further implicate IL6ST as a genetic susceptibility factor for CAD and MI in humans. Thus, the acute phase reaction should be considered an important target for future drug development in the management of CAD.

Prognostic Impact of the Get-with-the-Guidelines Heart-Failure Risk Score (GWTG-HF) after Transcatheter Aortic Valve Replacement in Patients with Low-Flow-Low-Gradient Aortic Valve Stenosis.

OBJECTIVES: This study examined the prognostic value of the get-with-the-guidelines heart-failure risk score (GWTG-HF) on mortality in patients with low-flow-low-gradient aortic valve stenosis (LFLG-AS) after transcatheter aortic valve implantation (TAVI). BACKGROUND: Data on feasibility of TAVI and mortality prediction in the LFLG-AS population are scarce. Clinical risk assessment in this particular population is difficult, and a score has not yet been established for this purpose. METHODS: A total of 212 heart failure (HF) patients with real LFLG-AS were enrolled. Patients were classified into low-risk (n = 108), intermediate-risk (n = 90) and high-risk (n = 14) groups calculated by the GWTG-HF score. Clinical outcomes of cardiovascular events according to Valve Academic Research Consortium (VARC-2) recommendations and composite endpoint of death and hospitalization for heart failure (HHF) were assessed at discharge and 1 year of follow-up. RESULTS: Baseline parameters of the groups showed a median age of 81.0 years [77.0; 84.0] (79.0 vs. 82.0 vs. 86.0, respectively p < 0.001), median EuroSCORE II of 6.6 [4.3; 10.7] (5.5 vs. 7.2 vs. 9.1, p = 0.004) and median indexed stroke volume of 26.7 mL/m2 [22.0; 31.0] (28.2 vs. 25.8 vs. 25.0, p = 0.004). The groups significantly differed at follow-up in terms of all-cause mortality (10.2 vs. 21.1 vs. 28.6%; p < 0.035). There was no difference in intrahospital event rate (VARC). Postprocedural mean gradients were lower in high-risk group (7.0 vs. 7.0 vs. 5.0 mmHg, p = 0.011). No differences in postprocedural aortic valve area (1.9 vs. 1.7 vs. 1.9 cm2, p = 0.518) or rate of device failure (5.6 vs. 6.8 vs. 7.7%, p = 0.731) could be observed. After adjustment for known predictors, the GWTG score (HR 1.07 [1.01-1.14], p = 0.030) as well as pacemaker implantation (HR 3.97 [1.34-11.75], p = 0.013) turned out to be possible predictors for mortality. An increase in stroke volume index (SVI) was, in contrast, protective (HR 0.90 [0.83-0.97]; p = 0.006). CONCLUSIONS: The GWTG score may predict mortality after TAVI in LFLG-AS HF patients. Interestingly, all groups showed similar intrahospital event and mortality rates, independent of calculated mortality risk. Low SVI and new conduction disturbances associated with PPI after THV implantation had negative impact on mid-term outcome in post-TAVI HF-patients.

Procedural Outcomes of a Self-Expanding Transcatheter Heart Valve in Patients with Porcelain Aorta.

BACKGROUND: Severe calcification of the ascending aorta increases the peri-operative risk for neurological complications in patients with severe aortic stenosis. Transcatheter aortic valve implantation (TAVI) seems to be an optimal treatment option in these patients. However, the impact of the extent of aortic calcification on procedural and neurological outcomes during TAVI is unclear. METHODS: Data from 3010 patients with severe native aortic valve stenosis treated with ACURATE neo/neo2 from May 2012 to July 2022 were evaluated and matched by 2-to-1 nearest-neighbor matching to identify one patient with porcelain aorta (PA) (n = 492) compared with two patients without PA (n = 984). PA was additionally subdivided into circumferential (classic PA) (n = 89; 3.0%) and non-circumferential (partial PA) (n = 403; 13.4%) calcification. We compared outcomes according to VARC-3 criteria among patients with and without PA and identified predictors for occurrence of stroke in the overall population. RESULTS: Technical success (88.5% vs. 87.4%, p = 0.589) and device success at 30 days (82.3% vs. 81.5%, p = 0.755) after transcatheter ACURATE neo/neo2 implantation according to VARC-3 definition was high and did not differ between non-calcified aortas or PA. The rate of in-hospital complications according to VARC-3-definitions was low in both groups. Rates of all stroke (3.2% (n = 31) vs. 2.6% (n = 13), p = 0.705) or transitory ischemic attacks (1.1% vs. 1.2%, p = 1.000) did not differ significantly. Thirty-day all-cause mortality did not differ (3.0% vs. 3.2%, RR 1.1; p = 0.775). Overall device migration/embolization (OR 5.0 [2.10;11.87]), severe bleeding (OR 1.79 [1.11;2.89]), and major structural cardiac complications (OR 3.37 [1.32;8.57]) were identified as independent predictors for in-hospital stroke in a multivariate analysis after implantation of ACURATE neo/neo2. CONCLUSION: A porcelain aorta does not increase the risk of neurological complications after transfemoral ACURATE neo/neo2 implantation. Based on these findings, transfemoral ACURATE neo/neo2 implantation is safe in these particularly vulnerable patients.

Comparison of the New-Generation Self-Expanding NAVITOR Transcatheter Heart Valve with Its Predecessor, the PORTICO, in Severe Native Aortic Valve Stenosis.

BACKGROUND: Third-generation transcatheter heart valves (THVs) are designed to improve outcomes. Data on the new intra-annular self-expanding NAVITOR are scarce. AIMS: The aim of this analysis was to compare outcomes between the PORTICO and the NAVITOR systems. METHODS: Data from 782 patients with severe native aortic stenosis treated with PORTICO (n = 645) or NAVITOR (n = 137) from 05/2012 to 09/2022 were evaluated. The clinical and hemodynamic outcomes of 276 patients (PORTICO, n = 139; NAVITOR, n = 137) were evaluated according to VARC-3 recommendations. RESULTS: Rates of postprocedural more-than-mild paravalvular leakage (PVL) were significantly lower for NAVITOR than for PORTICO (7.2% vs. 1.5%, p = 0.041). In addition, severe bleeding rates (27.3% vs. 13.1%, p = 0.005) and major vascular complications (5.8% vs. 0.7%, p = 0.036) were lower in the NAVITOR group. The mean gradients (7 vs. 8 mmHg, p = 0.121) and calculated aortic valve areas (1.90 cm2 vs. 1.99 cm2, p = 0.235) were comparable. Rates of PPI were similarly high in both groups (15.3 vs. 21.6, p = 0.299). CONCLUSIONS: The NAVITOR demonstrated favorable in-hospital procedural outcome data, with lower rates of relevant PVL, major vascular complications, and severe bleeding than its predecessor the PORTICO and preserved favorable hemodynamic outcomes.

Long-term follow-up of patients with complex coronary artery disease treated with minimally invasive direct coronary artery bypass.

BACKGROUND: Patients with complex coronary artery disease (CAD) may benefit from surgical myocardial revascularization but weighing the risk of peri-operative complications against the expected merit is difficult. Minimally invasive direct artery bypass (MIDCAB) procedures are less invasive, provide the prognostic advantage of operative revascularization of the left anterior descending artery and may be integrated in hybrid strategies. Herein, the outcomes between patients with coronary 1-vessel disease (1-VD) and patients with 2-VD and 3-VD after MIDCAB procedures were compared in this single-center study. METHODS: Between 1998 and 2018, 1363 patients underwent MIDCAB at the documented institution. 628 (46.1%) patients had 1-VD, 434 (31.9%) patients 2-VD and 300 (22.0%) patients suffered from 3-VD. Data of patients with 2-VD, and 3-VD were pooled as multi-VD (MVD). RESULTS: Patients with MVD were older (66.2 ± 10.9 vs. 62.9 ± 11.2 years; p < 0.001) and presented with a higher EuroScore II (2.10 [0.4; 34.2] vs. 1.2 [0.4; 12.1]; p < 0.001). Procedure time was longer in MVD patients (131.1 ± 50.3 min vs. 122.2 ± 34.5 min; p < 0.001). Post-operatively, MVD patients had a higher stroke rate (17 [2.3%] vs. 4 [0.6%]; p = 0.014). No difference in 30-day mortality was observed (12 [1.6%] vs. 4 [0.6%]; p = 0.128). Survival after 15 years was significantly lower in MVD patients (p < 0.01). Hybrid procedures were planned in 295 (40.2%) patients with MVD and realized in 183 (61.2%) cases. MVD patients with incomplete hybrid procedures had a significantly decreased long-term survival compared to cases with complete revascularization (p < 0.01). CONCLUSIONS: Minimally invasive direct coronary artery bypass procedures are low-risk surgical procedures. If hybrid procedures have been planned, completion of revascularization should be a major goal.

One-Year Outcomes According to Mitral Regurgitation Etiology Following Transcatheter Edge-to-Edge Repair With the PASCAL System: Results From a Multicenter Registry.

BACKGROUND: We previously reported procedural and 30-day outcomes of a German early multicenter experience with the PASCAL system for severe mitral regurgitation (MR). This study reports 1-year outcomes of mitral valve transcatheter edge-to-edge repair with the PASCAL system according to MR etiology in a large all-comer cohort. METHODS AND RESULTS: Clinical and echocardiographic outcomes up to 1-year were investigated according to MR etiology (degenerative [DMR], functional [FMR], or mixed [MMR]) in the first 282 patients with symptomatic MR 3+/4+ treated with the PASCAL implant at 9 centers in 2019. A total of 282 patients were included (33% DMR, 50% FMR, 17% MMR). At discharge, MR reduction to ≤1+/2+ was achieved in 58%/87% of DMR, in 75%/97% of FMR, and in 78%/98% of patients with MMR (P=0.004). MR reduction to ≤1+/2+ was sustained at 30 days (50%/83% DMR, 67%/97% FMR, 74%/100% MMR) and at 1 year (53%/78% DMR, 75%/97% FMR, 67%/91% MMR) with significant differences between etiologies. DMR patients with residual MR 3+/4+ at 1-year had at least complex valve morphology in 91.7%. Valve-related reintervention was performed in 7.4% DMR, 0.7% FMR, and 0.0% MMR (P=0.010). At 1-year, New York Heart Association Functional Class was significantly improved irrespective of MR etiology (P<0.001). CONCLUSIONS: In this large all-comer cohort, mitral valve transcatheter edge-to-edge repair with the PASCAL system was associated with an acute and sustained MR reduction at 1-year in all causes. However, in patients with DMR, MR reduction was less pronounced, reflecting the high incidence of complex or very complex anatomies being referred for mitral valve transcatheter edge-to-edge repair.

Toll-like receptor 2/6 stimulation promotes angiogenesis via GM-CSF as a potential strategy for immune defense and tissue regeneration.

Toll-like receptors (TLRs) are known primarily as pathogen recognition receptors of the innate immunity, initiating inflammatory pathways to organize the immune defense. More recently, an involvement of TLRs in various physiologic and pathologic processes has been reported. Because many of these processes implicate angiogenesis, we here elucidated the role of a TLR2/6-dependent pathway on angiogenesis using the TLR2/6 agonist macrophage-activating lipopeptide of 2 kDa (MALP-2), a common bacterial lipopeptide. In vivo and in vitro Matrigel assays demonstrated that MALP-2 promoted angiogenesis in a TLR2/6-dependent manner. Moreover, MALP-2 induced endothelial cell proliferation and migration and a strong secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF release in response to MALP-2 from isolated vascular segments was completely prevented when the endothelium was removed. MALP-2 containing Matrigel implants exhibited vascular structures as well as CD45(+) cells. MALP-2 induced migration of leukocytes and likewise GM-CSF release, particularly from the monocyte population. Inhibition of GM-CSF by siRNA or antibodies suppressed MALP-2-induced angiogenesis in vitro and in vivo. These results clearly identified a TLR2/6-dependent induction of angiogenesis by the bacterial lipopeptide MALP-2, which is mediated by GM-CSF. This might represent a general mechanism to enhance or restore blood flow and recruit immune cells for pathogen defense and tissue regeneration.

Impact of an interleukin-1 receptor antagonist and erythropoietin on experimental myocardial ischemia/reperfusion injury.

BACKGROUND: Revascularization of infarcted myocardium results in release of inflammatory cytokines mediating myocardial reperfusion injury and heart failure. Blockage of inflammatory pathways dampens myocardial injury and reduces infarct size. We compared the impact of the interleukin-1 receptor antagonist Anakinra and erythropoietin on myocardial ischemia/reperfusion injury. In contrast to others, we hypothesized that drug administration prior to reperfusion reduces myocardial damage. METHODS AND RESULTS: 12-15 week-old Lewis rats were subjected to myocardial ischemia by a 1 hr occlusion of the left anterior descending coronary artery. After 15 min of ischemia, a single shot of Anakinra (2 mg/kg body weight (bw)) or erythropoietin (5000 IE/kg bw) was administered intravenously. In contrast to erythropoietin, Anakinra decreased infarct size (P < 0.05, N = 4/group) and troponin T levels (P < 0.05, N = 4/group). CONCLUSION: One-time intravenous administration of Anakinra prior to myocardial reperfusion reduces infarct size in experimental ischemia/reperfusion injury. Thus, Anakinra may represent a treatment option in myocardial infarction prior to revascularization.

Transcatheter-based aortic valve replacement vs. isolated surgical aortic valve replacement in 2020.

BACKGROUND: Based on the results of several recent randomized trials, European and American guidelines on valvular heart disease management have substantially expanded the indications for transcatheter aortic valve implantation (TAVI). We present an all-comer data on peri-operative risk profile and in-hospital outcomes from Germany for patients treated by TAVI or isolated surgical aortic valve replacement (iSAVR) in 2020, providing an opportunity to compare study data with data from daily clinical practice. METHODS: Data concerning all isolated aortic valve procedures performed in Germany in 2020 were retrieved from the mandatory nationwide quality control program. Expected mortality was calculated with the annually revised German Aortic valve score (AKL-score) based on the data of either catheter-based (AKL-CATH) or isolated surgical (AKL-CHIR) aortic valve replacement in Germany from the previous year (2019). RESULTS: In 2020 21,903 TAVI procedures (20,810 transvascular (TV; vs. 2019: 22.973; - 9.4%), 1093 transapical (TA; vs. 2019: 1413; - 22.6%)) and 6144 (vs. 2019 7905; - 22.5%) iSAVR were performed in Germany. Patients who received TAVI showed a significantly higher perioperative risk profile than patients undergoing iSAVR based on older age and more severe co-morbidities. While in-hospital mortality after TAVI (2.3%) was numerically lower than in 2019 (2.5%), this difference was not significant (p = 0.11). In-hospital mortality after iSAVR was identical in 2020 and 2019 (2.8%) and thus higher than after TAVI (p = 0.003), resulting in an observed expected mortality ratio of 1.02 after TAVI and 1.05 after iSAVR. After exclusion of the emergency procedures, in-hospital mortality did not differ significantly between the groups (TAVI 2.2% vs. iSAVR 1.9%, p = 0.26). CONCLUSION: Total numbers of both iSAVR and TAVI in Germany were lower in 2020 than in 2019, most likely due to the COVID-19 pandemic. However, the relative number of patients treated by TAVI as compared to iSAVR continues to increase. Despite older age and more severe comorbidities compared to patients undergoing iSAVR the in-hospital mortality after TAVI continued to decrease in 2020 and remains significantly lower than after iSAVR.

Outcome after surgical embolectomy for acute pulmonary embolism.

AIMS: Patients with pulmonary embolism (PE) and contraindications for or failed thrombolysis are at the highest risk for PE-related fatal events. These patients may benefit from surgical embolectomy, but data concerning this approach are still limited. METHODS: The method used here was retrospective data analysis of 103 patients who underwent surgical embolectomy from 2002 to 2020 at our department. RESULTS: Mean age was 58.4 (±15.1) years. Fifty-eight (56.3%) patients had undergone recent surgery; the surgery was tumor associated in 32 (31.1%) cases. Thirty (29.1%) patients had to be resuscitated due to PE, and 13 (12.6%) patients underwent thrombolysis prior to pulmonary embolectomy. Fifteen (14.5%) patients were placed on extra corporeal membrane oxygenation (ECMO) peri-operatively. Five patients (4.9%) died intra-operatively. Neurological symptoms occurred in four patients (3.9%). Thirty-day mortality was 23.3% ( n  = 24). Re-thoracotomy due to bleeding was necessary in 12 (11.6%) patients. This parameter was also identified as an independent risk factor for mortality. CONCLUSION: Surgical pulmonary embolectomy resulted in survival of the majority of patients with PE and contraindications for or failed thrombolysis. Given the excessive mortality when left untreated, an operative approach should become a routine part of discussions concerning alternative treatment options for these patients.

Multi-Center Comparison of Two Self-Expanding Transcatheter Heart Valves: A Propensity Matched Analysis.

BACKGROUND: During the last years, several transcatheter aortic heart valves entered the clinical market and are commercially available. The prostheses differ regarding several technical and functional aspects. However, little is known regarding head-to-head comparative data of the ACURATE neo and the PORTICO valve prostheses. OBJECTIVES: The aim of this study was to compare two self-expanding transcatheter aortic heart valves (THV), the ACURATE neo and the PORTICO, with regard to in-hospital and 30-day outcomes, as well as early device failures. METHODS: A total of 1591 consecutive patients with severe native aortic valve stenosis from two centers were included in the analyses and matched by 1:1 nearest neighbor matching to identify one patient treated with PORTICO (n = 344) for each patient treated with ACURATE neo (n = 344). RESULTS: In-hospital complications were comparable between both valves, including any kind of stroke (ACURATE neo = 3.5% vs. PORTICO = 3.8%; p = 1.0), major vascular complications (ACURATE neo = 4.5% vs. PORTICO = 5.4%; p = 0.99) or life-threatening bleeding (ACURATE neo = 1% vs. PORTICO = 2%; p = 0.68). The rate of device failure defined by the VARC-2 criteria were comparable, including elevated gradients and moderate-to-severe paravalvular leakage (ACURATE neo = 7.3% vs. PORTICO = 7.6%; p = 1.0). However, the need for permanent pacemaker implantation (PPI) was significantly more frequent after the use of PORTICO THV (9.5% vs. 18.7%; p = 0.002). CONCLUSIONS: In this two-center case-matched comparison, short-term clinical and hemodynamic outcomes showed comparable results between PORTICO and ACURATE neo prostheses. However, PORTICO was associated with a significant higher incidence of PPI.