Association of HbA1c and utilization of internal mammary arteries with wound infections in CABG.

Background: Deep sternal wound infection (DSWI) remains a serious complication after coronary artery bypass grafting (CABG). We herein aimed to stratify diabetic patients who underwent CABG using bilateral internal mammary artery (BIMA) for levels of glycated hemoglobin A1C (HbA1c) and compare postoperative outcomes. Methods: Between January 2010 and August 2020, 4,186 consecutive patients underwent isolated CABG at our center. In 3,229 patients, preoperative HbA1c levels were available. Primary endpoints were wound healing disorder (WHD), DSWI, and 30-day mortality. Patients were stratified according to preoperative HbA1c levels. Patients were further divided into subgroups according to utilization of BIMA. Results: After adjustment, no differences in mortality and stroke rates were seen between group 1 (HbA1c < 6.5%) vs. group 2 (HbA1c ≥ 6.5%). WHD was more frequent in group 2 [2.8 vs. 5.6%; adjusted p = 0.002; adjusted odds ratio (OR), 1.853 (1.243-2.711)] but not DSWI [1.0 vs. 1.5%; adjusted p = 0.543; adjusted OR, 1.247 (0.612-2.5409)]. BIMA use showed a higher rate of WHD [no BIMA: 3.0%; BIMA: 7.7%; adjusted p = 0.002; adjusted OR, 4.766 (1.747-13.002)] but not DSWI [no BIMA: 1.1%; BIMA: 1.8%; adjusted p = 0.615; adjusted OR, 1.591 (0.260-9.749)] in patients with HbA1c ≥ 6.5%. Conclusions: Intraoperative utilization of BIMA is not connected with an increase of DSWI but higher rates of WHD in patients with poor diabetic status and HbA1c ≥ 6.5%. Therefore, application of BIMA should be taken into consideration even in patients with poor diabetic status, while identification of special subsets of patients who are at particular high risk for DSWI is of paramount importance to prevent this serious complication.

Balloon-expandable transcatheter heart valves for treatment of aortic valve stenosis in patients with large aortic annuli: Evaluation of deployment balloon overfilling strategies.

OBJECTIVES: Transcatheter aortic valve implantation (TAVI) using balloon-expandable (BE) transcatheter heart valves (THV) in aortic annuli above 29 mm includes particular procedural steps, mainly involving overfilling of the deployment balloon. Data on overfilling strategies in clinical daily practice is scarce. We herein aimed for a retrospective description of utilized overfilling strategies in those patients. METHODS: Between January 2016 and December 2022, 45 patients (100% male, 76.9 ± 6.1 years) received TAVI in aortic annuli above 29 mm using a BE THV. Overfilling volumina of the deployment balloon were left to operators' discretion. Clinical and multislice computed tomography data were retrospectively collected. Clinical endpoints were adjudicated in accordance with the updated standardized VARC-3 definitions. RESULTS: Profound overfilling (+4/5 mL) was used in patients with a mild calcium burden (˂750 mm³) even in aortic annuli of 29.0-30.0 mm. Nominal/slight overfilling (+1 mL) was used in aortic annuli up to 32.5 mm but an intermediate to severe calcific burden (>750-3200 mm³). Accordingly, a low calcification group (˂750 mm³, n = 17) compared to a significant calcification group (≥750 mm³, n = 28), presented with higher overfilling volumina (2.1 ± 1.4 vs. 0.8 ± 1.0; p ˂ 0.001), although aortic annulus diameter was not different (29.8 ± 0.8 vs. 29.9 ± 0.9 mm; p = 0.7). All-cause 30-day mortality was 0%. Device success was 97.8%. Transvalvular mean pressure gradient at discharge was 9.5 ± 3.6 mmHg. No case of PVL >mild was documented. CONCLUSION: Extent of overfilling of the deployment balloon largely depends on calcification burden in addition to aortic annulus diameter with significant and profound overfilling particularly in patients with a calcification burden of the aortic valve complex ˂750 mm³.

Valve-in-valve procedures for degenerated surgical and transcatheter aortic valve bioprostheses using a latest-generation self-expanding intra-annular transcatheter heart valve.

Background: Valve-in-valve (ViV) transfemoral transcatheter aortic valve implantation (TAVI) for failing aortic surgical bioprostheses or transcatheter heart valves (THV) has demonstrated a reasonable clinical and hemodynamic efficacy. Traditionally, self-expanding (SE) supra-annular THV are considered to result in superior hemodynamics compared with balloon-expandable intra-annular THV after ViV. However, so far no data are found on latest-generation intra-annular SE THV for aortic ViV procedures which might be superior with regard to coronary access or subsequent valve reintervention. Aim: We herein aim to evaluate a latest-generation SE intra-annular THV for aortic ViV procedures. Materials and methods: Between May 2022 and November 2022, five consecutive patients (4/5 female with mean age of 76.2 years and mean Society of Thoracic Surgeons predicted risk of mortality score of 2.9%) received ViV TAVI using the Navitor system (Abbott, Chicago, IL, USA) for treatment of failing surgical bioprostheses or THV. Data were retrospectively analyzed according to updated Valve Academic Research Consortium 3 (VARC-3) definitions. Results: At 30 days, absence of mortality and VARC-3 adjudicated clinical endpoints were documented. Echocardiography at 30 days revealed complete absence of paravalvular leakage and single-digit mean transvalvular gradients (mean of 6.0 mmHg) in all patients. Conclusion: The investigated intra-annular SE THV results in excellent 30-day outcomes for aortic ViV procedures for failing surgical bioprostheses or THV. Despite the intra-annular design, hemodynamic results were excellent, even in small bioprostheses. Ease of use of this valve platform is reflected by only two cycles of resheathing in five ViV procedures with hemodynamic stability during all steps of valve deployment.

Fully Endoscopic Mitral Valve Repair with Percutaneous Cannulation of Groin Vessels.

Endoscopic mitral valve surgery (EMS) has become a standard of care at specialized heart centers, further reducing surgical trauma compared to a traditional minimally invasive, thoracotomy-based approach. Exposure of the groin vessels for the establishment of cardiopulmonary bypass (CPB) via surgical cutdown in minimally invasive surgery (MIS) may result in wound healing disorders or seroma formation. The avoidance of surgical exposure of the groin vessels by using fully percutaneous techniques for the insertion of a CPB cannula with the implementation of vascular pre-closure devices has the potential to reduce these complications and improve clinical results. Herein, we present the utilization of a novel plug based vacsular closure device with a resobable collagen plug and the absence of suture material for closure of the arterial access for CPB in MIS. While this device was initially predominantly used in transcatheter aortic valve implantation (TAVI) procedures, with its safety and feasibility shown, we herein show that it can be used in CPB cannulation, since it is capable of closing arterial access sites up to 25 French (Fr.) in size. This device may be suitable to significantly reduce groin complications in MIS and simplify the establishment of CPB. Here, we describe the fundamental steps of EMS, including percutaneous groin cannulation and decannulation using a vascular closure device.

Effect of periprocedural furosemide-induced diuresis with matched isotonic intravenous hydration in patients with chronic kidney disease undergoing transcatheter aortic valve implantation.

BACKGROUND: Acute kidney injury (AKI) after transcatheter aortic valve implantation (TAVI) is a serious complication which is associated with increased mortality. The RenalGuard system was developed to reduce the risk of AKI after contrast media exposition by furosemide-induced diuresis with matched isotonic intravenous hydration. The aim of this study was to examine the effect of the RenalGuard system on the occurrence of AKI after TAVI in patients with chronic kidney disease. METHODS: The present study is a single-center randomized trial including patients with severe aortic valve stenosis undergoing TAVI. Overall, a total of 100 patients treated by TAVI between January 2017 and August 2018 were randomly assigned to a periprocedural treatment with the RenalGuard system or standard treatment by pre- and postprocedural intravenous hydration. Primary endpoint was the occurrence of AKI after TAVI, and secondary endpoints were assessed according to valve academic research consortium 2 criteria. RESULTS: Overall, the prevalence of AKI was 18.4% (n = 18). The majority of these patients developed mild AKI according to stage 1. Comparing RenalGuard to standard therapy, no significant differences were observed in the occurrence of AKI (RenalGuard: 21.3%; control group: 15.7%; p = 0.651). In addition, there were no differences between the groups with regard to 30-day and 12-month mortality and procedure-associated complication rates. CONCLUSION: In this randomized trial, we did not detect a reduction in AKI after TAVI by using the RenalGuard system. A substantial number of patients with chronic kidney disease developed AKI after TAVI, whereas the majority presented with mild AKI according to stage 1 (ClinicalTrials.gov number NCT04537325).

Early commercial experience with a newly designed balloon-expandable transcatheter heart valve: 30-day outcomes and implications of preprocedural computed tomography.

OBJECTIVES: We herein report a single-centre experience with the SAPIEN 3 Ultra balloon-expandable transcatheter aortic valve implantation (TAVI) system. METHODS: Between March 2019 and January 2020, a total of 79 consecutive patients received transfemoral TAVI using the SAPIEN 3 Ultra device. Data were retrospectively analysed according to updated Valve Academic Research Consortium-2 definitions. Detailed analysis of multislice computed tomography data was conducted to identify potential predictors for permanent pacemaker (PPM) implantation and residual paravalvular leakage (PVL) post TAVI. RESULTS: Device success and early safety were 97.5% (77/79) and 94.9% (75/79) with resulting transvalvular peak/mean pressure gradients of 21.1 ± 8.2/10.9 ± 4.4 and PVL >mild in 0/79 patients (0%). Mild PVL was seen in 18.9% (15/79) of cases. Thirty-day mortality was 2.5% (2/79). The Valve Academic Research Consortium-2 adjudicated clinical end points disabling stroke, acute kidney injury and myocardial infarction occurred in 1.3% (1/79), 5.1% (4/79) and 0% (0/79) of patients. Postprocedural PPM implantation was necessary in 7.6% (6/79) of patients. Multislice computed tomography analysis revealed significantly higher calcium amounts of the right coronary cusp in patients in need for postprocedural PPM implantation and a higher eccentricity index in patients with postinterventional mild PVL. CONCLUSIONS: First experience with this newly designed balloon-expandable-transcatheter heart valve demonstrates adequate 30-day outcomes and haemodynamic results with low mortality, low rates of PPM implantation and no residual PVL >mild. The herein-presented multislice computed tomography values with an elevated risk for PPM implantation and residual mild PVL may help to further improve outcomes with this particular transcatheter heart valve in TAVI procedures.

TAVI in Patients with Mitral Annular Calcification and/or Mitral Stenosis.

BACKGROUND: We herein aimed for analysis of influence of mitral annular calcification (MAC) and mitral stenosis (MS) on outcomes in transcatheter aortic valve implantation (TAVI). METHODS: Between 11/2009 and 06/2017, 1,058 patients underwent TAVI in the presence of concomitant MAC or MS at our center. Subgroups were built and multivariate logistic regression, COX regression, Kaplan-Meier survival analyses, and receiver operating characteristics method were performed. RESULTS: Thirty-day mortality was 7.5% (79/1,058) with highest mortality in patients severe MS (MAC: 3.4% vs. mild MS: 5.9% vs. moderate MS: 15.0% vs. severe MS: 72.7%; p < 0.001). Moderate-to-severe MS (odds ratio [OR]: 7.75, confidence interval [CI]: 3.94-16.26, p < 0.001), impaired left ventricular ejection fraction (OR: 1.38, CI: 1.10-1.72, p < 0.01), and coronary artery disease (OR: 1.36, CI: 1.11-1.67, p < 0.01) were predictive of 30-day survival. Left ventricular systolic/end-diastolic pressure drop of <59.5 mm Hg / <19.5 mm Hg was associated with increased mortality. CONCLUSIONS: TAVI in the presence of MAC and mild MS is associated with acceptable acute outcomes but should be considered high-risk procedures in patients with moderate and especially those with severe MS. Our results suggest adverse hemodynamics after TAVI with concomitant MS, which may be caused by underfilling of the left ventricle leading to low-cardiac output.

Spontaneous echo contrast, left atrial appendage thrombus and stroke in patients undergoing transcatheter aortic valve implantation.

AIMS: The relevance of spontaneous echo contrast (SEC) and left atrial appendage thrombus (LAAT) in patients undergoing transcatheter aortic valve implantation (TAVI) remains unclear. In this study, we aimed to assess the prevalence of SEC and LAAT and evaluate the impact on periprocedural outcome after TAVI. METHODS AND RESULTS: A total of 2,549 consecutive patients underwent TAVI between 2008 and 2017. After exclusion of cases with insufficient imaging, concomitant procedures or severe intraprocedural complications, 1,558 cases were analysed. Three groups were defined according to (pre)thrombotic formations - moderate or severe SEC (n=89), LAAT (n=53), and reference (n=1,416). The primary outcome was disabling ischaemic stroke within 24 hours. The prevalence was 4.4% for LAAT and 5.4% for moderate/severe SEC. The primary outcome occurred more frequently in patients with moderate/severe SEC (6.8%) compared to the reference (2.1%) and LAAT (1.9%) groups (p=0.020). SEC was identified as an independent risk factor for the primary outcome (OR 3.54 [95% CI: 1.30-9.61], p=0.013). LAAT was associated with an impaired unadjusted one-year survival (43.4%) compared to the SEC (27.3%) and reference groups (18.7%, p<0.001). CONCLUSIONS: SEC and LAAT were detected in a relevant number of patients undergoing TAVI. SEC may represent an important risk factor for intraprocedural stroke; increased mortality was observed in patients with LAAT.

TAVI for Pure Non-calcified Aortic Regurgitation Using a Self-Expandable Transcatheter Heart Valve.

Objectives: Transcatheter aortic valve implantation (TAVI) is routinely performed in patients with severe aortic stenosis (AS). For patients with pure non-calcified aortic regurgitation (AR) who are not suitable for open heart surgery no clear recommendations exist and use of TAVI has been largely off-label. We herein report a series of patients treated with the self-expandable AcurateNeo and Neo2 (Boston Scientific Co., Marlborough, MS, USA) transcatheter heart valve (THV) for pure AR. Methods: Between 05/2017 and 03/2021, 9 patients (88.8% female, 74.4 ± 7.1 years, logEuroSCORE II 5.5 ± 3.6%, STS PROM 6.2 ± 3.0%) received transfemoral (TF) TAVI for pure non-calcified AR following an adjusted valve sizing algorithm. Data were retrospectively analyzed according to updated Valve Academic Research Consortium (VARC-2) definitions. Results: Device success was 100%. Early safety was 77.7% (7/10), due to two (22.2%) cases of acute kidney injury. Thirty-day mortality was 0%, in seven (77.7%) patients no or trace paravalvular leakage (PVL) was seen and mild PVL in two (22.2%) patients at 30-day follow-up. No permanent pacemaker (PPM) was required during 30-day follow-up. Conclusion: In this series of selected patients using the Acurate neo THV for pure non-calcified AR, safety and efficacy were demonstrated. Thirty-day mortality as well as PPM implantation and PVL rates showed excellent results in this high-risk patient cohort. These results will have to be confirmed in larger patient cohorts.

Clinical outcomes of complete versus incomplete revascularization in patients treated with coronary artery bypass grafting: insights from the TiCAB trial.

OBJECTIVES: In this post hoc analysis of the Ticagrelor in coronary artery bypass grafting (CABG) trial, we aimed to analyse patients treated with CABG receiving either complete revascularization (CR) or incomplete revascularization (ICR) independent from random allocation to either ticagrelor or aspirin. METHODS: Of 1859 patients enrolled in the Ticagrelor in CABG trial, 1550 patients (83.4%) received CR and 309 patients (16.6%) ICR. Outcomes were evaluated regarding all-cause mortality, cardiovascular death, myocardial infarction (MI), repeat revascularization, stroke and bleeding within 12 months after CABG. RESULTS: Baseline parameters revealed significant differences regarding clinical presentation (stable angina pectoris: CR 68.9% vs ICR 71.2%, instable angina pectoris: 14.1% vs 7.8%, non-ST elevation MI: 17.0% vs 21.0%, P ˂ 0.01), lesion characteristics (chronic total occlusion: CR 91.3% vs ICR 96.8%, P ˂ 0.01), operative technique [off-pump coronary artery bypass surgery (OPCAB): CR 3.0% vs ICR 6.1%, P ˂ 0.01] and number of utilized grafts (total number of grafts: 2.69/patient vs 2.49/patient, P ˂ 0.001). ICR patients displayed a significantly increased risk of repeat revascularization [hazard ratio (HR) 1.91, 95% confidence interval (CI) 1.16-3.16; P < 0.01] and percutaneous coronary intervention (HR 1.95, 95% CI 1.13-3.35; P < 0.05) within 12 months after CABG. Higher risk for repeat revascularization in ICR patients was independent from random allocation to either ticagrelor or aspirin and persisted after adjustment for baseline imbalances. CONCLUSIONS: Patients with ICR presented more stable at the time of admission, but received less grafts, highly likely due to a higher rate of chronic total occlusion lesions and performed OPCAB. Although mortality presented no difference between groups, our results suggest that patients benefit from CR with regard to prevention of repeat revascularization.

Left Ventricular Assist Device Implantation and Concomitant Dor Procedure: a Single Center Experience.

OBJECTIVE: Left ventricular assist device (LVAD) implantation with concomitant Dor plasty is only reported anecdotally. We herein aimed to describe our experience with LVAD and concomitant Dor procedures and describe long-term outcomes of this special subset of heart failure patients. METHODS: Between January/2010 and December/2018, 144 patients received LVAD therapy at our institution. Of those, five patients (80% male, 60.4±7.2 years) presented with an apical aneurysm and received concomitant Dor plasty. Apical aneurysms presented diameter between 75 and 98 mm, with one impending rupture. RESULTS: Procedural success was achieved in all patients. No unplanned right ventricular assist device implantation occurred. Furthermore, no acute 30-day mortality was seen. In follow-up, one patient was lost due to intentional disconnection of the driveline. One patient underwent heart transplantation on postoperative day 630. The remaining three patients are still on device with sufficient flow; pump thromboses were successfully managed by lysis therapy in one patient. CONCLUSION: LVAD implantation with concomitant Dor procedure is feasible, safe, and occasionally performed in patients with ischemic cardiomyopathy. Major advantages are prevention of thromboembolism and facilitation of LVAD placement by improving pump stability and warranting midventricular, coaxial alignment of the inflow cannula. In long-term follow-up, no adverse event associated with Dor plasty was observed.

Left ventricular assist device implantation and concomitant dor procedure: a single center experience

Abstract Objective: Left ventricular assist device (LVAD) implantation with concomitant Dor plasty is only reported anecdotally. We herein aimed to describe our experience with LVAD and concomitant Dor procedures and describe long-term outcomes of this special subset of heart failure patients. Methods: Between January/2010 and December/2018, 144 patients received LVAD therapy at our institution. Of those, five patients (80% male, 60.4±7.2 years) presented with an apical aneurysm and received concomitant Dor plasty. Apical aneurysms presented diameter between 75 and 98 mm, with one impending rupture. Results: Procedural success was achieved in all patients. No unplanned right ventricular assist device implantation occurred. Furthermore, no acute 30-day mortality was seen. In follow-up, one patient was lost due to intentional disconnection of the driveline. One patient underwent heart transplantation on postoperative day 630. The remaining three patients are still on device with sufficient flow; pump thromboses were successfully managed by lysis therapy in one patient. Conclusion: LVAD implantation with concomitant Dor procedure is feasible, safe, and occasionally performed in patients with ischemic cardiomyopathy. Major advantages are prevention of thromboembolism and facilitation of LVAD placement by improving pump stability and warranting midventricular, coaxial alignment of the inflow cannula. In long-term follow-up, no adverse event associated with Dor plasty was observed.

Transcatheter aortic valve implantation versus surgical aortic valve replacement in low-risk patients: a propensity score-matched analysis.

OBJECTIVES: The aim of the study was to determine the differences in outcomes of surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI) in low-risk patients. METHODS: All patients with a logistic EuroSCORE II <4% who underwent transfemoral TAVI between 2008 and 2016 (n = 955) or SAVR between 2009 and 2014 (n = 886) at our centre were included. One hundred and nine patients per group were available for propensity score matching. RESULTS: Mortality during the 30-day follow-up showed no differences (SAVR vs TAVI: 1.1% vs 1.8%, P = 1.0) but the rates of permanent pacemaker implantation (0.0 vs 14.8%, P < 0.001) and paravalvular leakage ≥ moderate (0.0 vs 7.0%, P = 0.017) were higher in TAVI patients. No difference was found regarding postoperative effective orifice area and transvalvular pressure gradients. Although, the 1-year survival was similar between both groups; 3- and 5-year survival was significantly inferior in the TAVI patient cohort. CONCLUSIONS: TAVI yielded similar short-term outcomes compared with SAVR despite higher rates of permanent pacemaker implantation and paravalvular leakage ≥ moderate, but inferior long-term survival. Poorer long-term outcomes of the TAVI patient cohort were attributable to a more comorbid TAVI population. This emphasizes the need for long-term results from randomized controlled trials before TAVI can be broadly expanded to younger low-risk patients.

Analysis of fibrosis in control or pressure overloaded rat hearts after mechanical unloading by heterotopic heart transplantation.

Mechanical unloading (MU) by implantation of left ventricular assist devices (LVAD) has become clinical routine. This procedure has been shown to reverse cardiac pathological remodeling, with the underlying molecular mechanisms incompletely understood. Most studies thus far were performed in non-standardized human specimens or MU of healthy animal hearts. Our study investigates cardiac remodeling processes in sham-operated healthy rat hearts and in hearts subjected to standardized pathological pressure overload by transverse aortic constriction (TAC) prior to MU by heterotopic heart transplantation (hHTx/MU). Rats underwent sham or TAC surgery. Disease progression was monitored by echocardiography prior to MU by hHTx/MU. Hearts after TAC or TAC combined with hHTx/MU were removed and analyzed by histology, western immunoblot and gene expression analysis. TAC surgery resulted in cardiac hypertrophy and impaired cardiac function. TAC hearts revealed significantly increased cardiac myocyte diameter and mild fibrosis. Expression of hypertrophy associated genes after TAC was higher compared to hearts after hHTx/MU. While cardiac myocyte cell diameter regressed to the level of sham-operated controls in all hearts subjected to hHTx/MU, fibrotic remodeling was significantly exacerbated. Transcription of pro-fibrotic and apoptosis-related genes was markedly augmented in all hearts after hHTx/MU. Sarcomeric proteins involved in excitation-contraction coupling displayed significantly lower phosphorylation levels after TAC and significantly reduced total protein levels after hHTx/MU. Development of myocardial fibrosis, cardiac myocyte atrophy and loss of sarcomeric proteins was observed in all hearts that underwent hHTX/MU regardless of the disease state. These results may help to explain the clinical experience with low rates of LVAD removal due to lack of myocardial recovery.

Prosthesis-patient mismatch after transcatheter aortic valve implantation: prevalence and prognostic impact with respect to baseline left ventricular function.

AIMS: We aimed to assess the prevalence and features of prosthesis-patient mismatch (PPM) following transcatheter aortic valve implantation (TAVI) and its prognostic impact considering baseline left ventricular ejection fraction (LVEF). METHODS AND RESULTS: Data from 1,309 patients undergoing TAVI for severe aortic stenosis were derived from a single-centre dedicated TAVI registry. PPM was assessed according to echocardiography at discharge and was defined in accordance with VARC-2. Median follow-up time was 2.03 years. Moderate and severe PPM was detected in 22.9% and 12.9%, respectively. Patients with severe PPM had smaller annuli and more often received transcatheter heart valve (THV) sizes ≤23 mm. Supra-annular THV design showed the lowest rate of PPM. In patients with LVEF <40%, but not in those with LVEF ≥40%, severe PPM was associated with an increased three-year mortality rate (no vs. severe PPM for LVEF ≥40%: 34.6% vs. 29.5%, p=0.96; LVEF <40%: 45.1% vs. 68.0%, p=0.041) and was independently predictive of all-cause mortality according to multivariate analysis in these patients (HR 2.97; 95% CI: 1.58-5.59, p<0.001). CONCLUSIONS: The presence of severe PPM depends on annular dimensions and THV size and design and is an independent predictor of mortality in patients with reduced LVEF. Hence, the risk of PPM should be considered within the process of THV selection.

Transcatheter aortic valve implantation utilizing a non-occlusive balloon for predilatation.

BACKGROUND: Balloon aortic valvuloplasty (BAV) is routinely performed preceding transcatheter aortic valve implantation (TAVI). Among risks inherent in BAV is low cardiac output due to rapid ventricular pacing (RVP), especially in patients with severely impaired left ventricular function. We herein report early experience utilizing a non-occlusive balloon for BAV (TrueFlow™, BARD, Peripheral Vascular, Tempe, AZ, US), which does not require RVP. METHODS: Between 11/2016 and 10/2017, 27 consecutive patients received TAVI using a non-occlusive balloon valvuloplasty catheter for predilatation and a self-expandable transcatheter heart valve (77.8% female, 81.7 ±â€¯6.6 years, logEuroSCORE I 15.8 ±â€¯10.3%, STS Prom Score 2.5 ±â€¯0.5%). Hemodynamic measurements and acute outcome data were analyzed according to updated Valve Academic Research Consortium definitions. RESULTS: Procedure time, fluoroscopy time and amount of contrast agent were 74.5 ±â€¯17.4 min, 16.7 ±â€¯6.9 min and 156.9 ±â€¯92.7 ml. Device success and early combined safety were 100% and 92.6% (25/27). Effective BAV without RVP after the first inflation was achieved in 92.6% of the patients (25/27). Continuous recording of hemodynamics documented no relevant systemic pressure drop during BAV. Postdilatation with a regular balloon was required in 10/27 patients. No death was observed during 30-day follow-up. Resultant mean transvalvular gradient was 6.0 ±â€¯3.5 mm Hg. In one patient a moderate paravalvular leakage was seen. CONCLUSIONS: In this series of TAVI utilizing a novel non-occlusive balloon, safety and efficacy were demonstrated. Adequate predilatation was achieved in all cases without need for RVP and with stable hemodynamics. These results will have to be confirmed in larger patient cohorts.

Transaxillary transcatheter aortic valve implantation utilizing a novel vascular closure device with resorbable collagen material: a feasibility study.

OBJECTIVES: We herein aimed to evaluate technical feasibility of transaxillary (Tax) transcatheter aortic valve implantation (TAVI) utilizing a novel vascular closure device with a resorbable collagen plug and absence of suture material. METHODS: Between 05/2018 and 8/2018, eight patients (76.0 ± 5.9 years, 62.5% male, logEuroSCORE I 23.6 ± 4.7) received Tax-TAVI using the MANTA™ vascular closure device. Implanted transcatheter heart valves consisted of Edwards Sapien 3, NVT Allegra, Medtronic CoreValve EvolutR and SJM Portico. RESULTS: Puncture location depth was variable (3.5-7.5 cm). The left subclavian artery was used in five cases, the right subclavian artery in three cases. Low-pressure balloon-angioplasty for vessel closure was performed in 5/8 patients. VARC-2 defined device success was met in all patients. Major access site complication occurred in one patient with aneurysma spurium of the subclavian artery and consecutive stent implantation on postoperative day 5. CONCLUSION: The MANTA™ device is applicable in Tax-TAVI, with potential particular advantages regarding easiness of use and marked access for subsequent interventions in case of vascular complications. Before conclusions regarding clinical efficacy and safety can be made, the device has to be evaluated in larger patient cohorts.

Pharmacological inhibition of DNA methylation attenuates pressure overload-induced cardiac hypertrophy in rats.

BACKGROUND: Heart failure is associated with altered gene expression and DNA methylation. De novo DNA methylation is associated with gene silencing, but its role in cardiac pathology remains incompletely understood. We hypothesized that inhibition of DNA methyltransferases (DNMT) might prevent the deregulation of gene expression and the deterioration of cardiac function under pressure overload (PO). To test this hypothesis, we evaluated a DNMT inhibitor in PO in rats and analysed DNA methylation in cardiomyocytes. METHODS AND RESULTS: Young male Wistar rats were subjected to PO by transverse aortic constriction (TAC) or to sham surgery. Rats from both groups received solvent or 12.5 mg/kg body weight of the non-nucleosidic DNMT inhibitor RG108, initiated on the day of the intervention. After 4 weeks, we analysed cardiac function by MRI, fibrosis with Sirius Red staining, gene expression by RNA sequencing and qPCR, and DNA methylation by reduced representation bisulphite sequencing (RRBS). RG108 attenuated the ~70% increase in heart weight/body weight ratio of TAC over sham to 47% over sham, partially rescued reduced contractility, diminished the fibrotic response and the downregulation of a set of genes including Atp2a2 (SERCA2a) and Adrb1 (beta1-adrenoceptor). RG108 was associated with significantly lower global DNA methylation in cardiomyocytes by ~2%. The differentially methylated pathways were "cardiac hypertrophy", "cell death" and "xenobiotic metabolism signalling". Among these, "cardiac hypertrophy" was associated with significant methylation differences in the group comparison sham vs. TAC, but not significant between sham+RG108 and TAC+RG108 treatment, suggesting that RG108 partially prevented differential methylation. However, when comparing TAC and TAC+RG108, the pathway cardiac hypertrophy was not significantly differentially methylated. CONCLUSIONS: DNMT inhibitor treatment is associated with attenuation of cardiac hypertrophy and moderate changes in cardiomyocyte DNA methylation. The potential mechanistic link between these two effects and the role of non-myocytes need further clarification.

Outcomes with a latest generation self-expandable, intra-annular, re-sheathable transcatheter heart valve system: analysis of patients with impaired left ventricular function and determinants for pacemaker implantation.

OBJECTIVES: We herein report a single-center experience with the Portico TAVI system. Main focus was set on outcomes in patients with impaired left ventricular (LV) function and predictors for permanent pacemaker (PPM) implantation. METHODS: Between 05/2014 and 10/2017, 106 consecutive patients received TAVI using the Portico device. For comparison of patients with/without impaired LV function, and determination of multi-slice computed tomography and electrocardiogram correlates for PPM implantation subgroups were built (Subgroup I: LVEF ≥ 50%, n = 69, Subgroup II: LVEF < 50%, n = 37; Subgroup A: no PPM implantation, n = 89; Subgroup B: PPM implantation, n = 17). Data were retrospectively analyzed. RESULTS: Device success was 95.3% (101/106) with resulting transvalvular peak/mean pressure gradients of 10.6 ± 5.6/5.4 ± 3.1 and PVL ≥ moderate in 5/106 patients (4.7%). 30-day mortality was 4.7% (5/106; subgroup I 3/69, 4.3%; subgroup II 2/37, 5.4%; p = 1.0). Regarding VARC-2 adjudicated clinical endpoints stroke (3/106, 2.8%; subgroups I/II: 2/69 vs. 1/37, p = 1.0) and acute kidney injury (9/106, 8.5%; subgroups I/II: 6/69 vs. 3/37, p = 1.0), no significant differences were found. Postprocedural PPM implantation occurred in 17.9% (19/106) of the patients. Logistic regression for PPM implantation demonstrated predictive character of left coronary cusp (LCC) calcium load in zone 1 (annular plane to coronary ostia) (p = 0.05, threshold 193 mm3) and total calcium load of zone 1 (p = 0.05, threshold 751.2 mm3). CONCLUSIONS: The Portico valve demonstrates a satisfying safety outcome, especially for patients with impaired LV function. Results of the CE-mark trial were confirmed, except for higher PPM rates. PPM rates are in accordance with other reports on this TAVI platform.

AkrinorTM, a Cafedrine/ Theodrenaline Mixture (20:1), Increases Force of Contraction of Human Atrial Myocardium But Does Not Constrict Internal Mammary Artery In Vitro.

Background: Intraoperative hypotension is a common problem and direct or indirect sympathomimetic drugs are frequently needed to stabilize blood pressure. AkrinorTM consists of the direct and the indirect sympathomimetic noradrenaline and norephedrine. Both substances are covalently bound to the phosphodiesterase (PDE) inhibitor theophylline, yielding theodrenaline and cafedrine, respectively. We investigated pharmacodynamic effects of AkrinorTM and its constituents on contractile force and tension in human atrial trabeculae and internal A. mammaria rings. Methods: Isometric contractions were measured in human atrial trabeculae at 1 Hz and 37°C. CGP 20712A and ICI 118,551 were used to elaborate ß1- and ß2-adrenoceptor (AR) subtypes involved and phenoxybenzamine to estimate indirect sympathomimetic action. PDE-inhibition was measured as a potentiation of force increase upon direct activation of adenylyl cyclase by forskolin. Human A. mammaria preparations were used to estimate intrinsic vasoconstriction and impact on the noradrenaline-induced vasoconstriction. Results: Clinically relevant concentrations of AkrinorTM (4.2-420 mg/l) robustly increased force in human atrial trabeculae (EC50 41 ± 3 mg/l). This direct sympathomimetic action was mediated via ß1-AR and the effect size was as large as with high concentrations of calcium. Only the highest and clinically irrelevant concentration of AkrinorTM increased the potency of forskolin to a minor extent. Norephedrine has lost its indirect sympathomimetic effect when bound to theophylline. Increasing concentrations of AkrinorTM (4.2-168 mg/l) alone did not affect the tension of human A. mammaria interna rings, but shifted the noradrenaline curve rightward from -logEC50 6.18 ± 0.08 to 5.23 ± 0.05 M. Conclusion: AkrinorTM increased cardiac contractile force by direct sympathomimetic actions and PDE inhibition, did not constrict A. mammaria preparations, but shifted the concentration-response curve to the right, compatible with an α-AR antagonistic effect or PDE inhibition. The pharmacodynamic profile and potency of AkrinorTM differs from noradrenaline and norephedrine in vitro. We anticipate metabolism of theodrenaline and cafedrine resulting in a different pharmacodynamic profile of AkrinorTMin vivo.