Florian Krackhardt’s research while affiliated with Charité Universitätsmedizin Berlin and other places

Background: Drug eluting stents (DES) are associated with a 2% to 4% annual rate of target lesion failure through 5-to-10-year follow-up. The presence of a metallic protheses is a trigger for neo-atherosclerosis and very late stent thrombosis. A "leave nothing behind" strategy using Drug Coated Balloons has been suggested; however, paclitaxel coated balloons are only recommended in selected indications. Recently a novel sirolimus eluting balloon, the SELUTION SLR TM 014 PTCA balloon (SEB) (M.A. MedAlliance SA, Nyon, Switzerland) has been developed. Hypothesis: A strategy of percutaneous coronary intervention (PCI) with SEB and provisional DES is non-inferior to a strategy of systematic DES on target vessel failure (TVF) at one and five years. If non-inferiority is met at 5 years, superiority will be tested. Design: SELUTION DeNovo is a multi-center international open-label randomized trial. Subjects meeting eligibility criteria are randomized 1:1 to treatment of all lesions with either SEB and provisional DES or systematic DES. Major inclusion criteria are PCI indicated for ≥1 lesion considered suitable for treatment by either SEB or DES and clinical presentation with chronic coronary syndrome, unstable angina or non-ST segment elevation (NSTEMI). There is no limitation in the number of lesions to be treated. Target lesions diameters are between 2 and 5 mm. Major exclusion criteria are lesions in the left main artery, chronic total occlusions, ST segment elevation myocardial infarction and unstable NSTEMI. 3326 patients will be included in 50 sites in Europe and Asia. TVF rates and their components will be determined at 30 days, 6 months and annually up to 5 years post-intervention. Among secondary endpoints, bleeding events, cost-effectiveness data and net clinical benefits will be assessed. Summary: SELUTION DeNovo trial is an open-label, multi-center international randomized trial comparing a strategy of PCI with SEB and provisional DES to a strategy of PCI with systematic DES on TVF at one and five years. Non-inferiority will be tested at one and five years. If non-inferiority is met at five years, superiority will be tested.

Background In most cases of transcatheter valve embolization and migration (TVEM), the embolized valve remains in the aorta after implantation of a second valve into the aortic root. There is little data on potential late complications such as valve thrombosis or aortic wall alterations by embolized valves. Aims The aim of this study was to analyze the incidence of TVEM in a large cohort of patients undergoing transcatheter aortic valve implantation (TAVI) and to examine embolized valves by computed tomography (CT) late after TAVI. Methods The patient database of our center was screened for cases of TVEM between July 2009 and July 2021. To identify risk factors, TVEM cases were compared to a cohort of 200 consecutive TAVI cases. Out of 35 surviving TVEM patients, ten patients underwent follow-up by echocardiography and CT. Results 54 TVEM occurred in 3757 TAVI procedures, 46 cases were managed percutaneously. Horizontal aorta (odds ratio [OR] 7.51, 95% confidence interval [CI] 3.4–16.6, p < 0.001), implantation of a self-expanding valve (OR 4.63, 95% CI 2.2–9.7, p < 0.01) and a left ventricular ejection fraction < 40% (OR 2.94, 95% CI 1.1–7.3, p = 0.016) were identified as risk factors for TVEM. CT scans were performed on average 26.3 months after TAVI (range 2–84 months) and detected hypoattenuated leaflet thickening (HALT) in two patients as well as parts of the stent frame protruding into the aortic wall in three patients. Conclusion TVEM represents a rare complication of TAVI. Follow up-CT detected no pathological findings requiring intervention.

Importance There is limited evidence on the benefits of sacubitril/valsartan vs broader renin angiotensin system inhibitor background therapy on surrogate outcome markers, 6-minute walk distance, and quality of life in patients with heart failure and mildly reduced or preserved left ventricular ejection fraction (LVEF >40%). Objective To evaluate the effect of sacubitril/valsartan on N-terminal pro–brain natriuretic peptide (NT-proBNP) levels, 6-minute walk distance, and quality of life vs background medication–based individualized comparators in patients with chronic heart failure and LVEF of more than 40%. Design, Setting, and Participants A 24-week, randomized, double-blind, parallel group clinical trial (August 2017-October 2019). Of 4632 patients screened at 396 centers in 32 countries, 2572 patients with heart failure, LVEF of more than 40%, elevated NT-proBNP levels, structural heart disease, and reduced quality of life were enrolled (last follow-up, October 28, 2019). Interventions Patients were randomized 1:1 either to sacubitril/valsartan (n = 1286) or to background medication–based individualized comparator (n = 1286), ie, enalapril, valsartan, or placebo stratified by prior use of a renin angiotensin system inhibitor. Main Outcomes and Measures Primary end points were change from baseline in plasma NT-proBNP level at week 12 and in the 6-minute walk distance at week 24. Secondary end points were change from baseline in quality of life measures and New York Heart Association (NYHA) class at 24 weeks. Results Among 2572 randomized patients (mean age, 72.6 years [SD, 8.5 years]; 1301 women [50.7%]), 2240 (87.1%) completed the trial. At baseline, the median NT-proBNP levels were 786 pg/mL in the sacubitril/valsartan group and 760 pg/mL in the comparator group. After 12 weeks, patients in the sacubitril/valsartan group (adjusted geometric mean ratio to baseline, 0.82 pg/mL) had a significantly greater reduction in NT-proBNP levels than did those in the comparator group (adjusted geometric mean ratio to baseline, 0.98 pg/mL) with an adjusted geometric mean ratio of 0.84 (95% CI, 0.80 to 0.88; P < .001). At week 24, there was no significant between-group difference in median change from baseline in the 6-minute walk distance with an increase of 9.7 m vs 12.2 m (adjusted mean difference, −2.5 m; 95% CI, −8.5 to 3.5; P = .42). There was no significant between-group difference in the mean change in the Kansas City Cardiomyopathy Questionnaire clinical summary score (12.3 vs 11.8; mean difference, 0.52; 95% CI, −0.93 to 1.97) or improvement in NYHA class (23.6% vs 24.0% of patients; adjusted odds ratio, 0.98; 95% CI, 0.81 to 1.18). The most frequent adverse events in the sacubitril/valsartan group vs the comparator group were hypotension (14.1% vs 5.5%), albuminuria (12.3% vs 7.6%), and hyperkalemia (11.6% vs 10.9%). Conclusions and Relevance Among patients with heart failure and left ventricular ejection factor of higher than 40%, sacubitril/valsartan treatment compared with standard renin angiotensin system inhibitor treatment or placebo resulted in a significantly greater decrease in plasma N-terminal pro–brain natriuretic peptide levels at 12 weeks but did not significantly improve 6-minute walk distance at 24 weeks. Further research is warranted to evaluate potential clinical benefits of sacubitril/valsartan in these patients. Trial Registration ClinicalTrials.gov Identifier: NCT03066804

Background Transcatheter valve embolization and migration (TVEM) is a potential complication of transcatheter aortic valve implantation (TAVI) (1). Registries suggest low incidence but clinical relevance due to increased acute and mid-term mortality with the majority embolizing in the aorta. However, there is little data on potential late complications such as leaflet and stent thrombosis or aortic wall alterations by migrated valves. Purpose The aim of our study was to analyze the incidence and clinical characteristics of TVEM in a large single center cohort of TAVI patients and to examine dislocated valves by ECG-gated computed tomography (CT). Methods and results Between July 2009 and May 2020, 40 TVEM occurred in 3387 TAVI procedures performed in our center (1.18%). TVEM was defined according to Valve Academic Research Consortium-2 (VARC-2) criteria (3). Majority of TVEM were left in the ascending aorta (31 ascending, 3 arch, 1 descending aorta). 90% of TVEM occurred with a self-expanding valve (SEV), with no difference between older and newer valve generations, 10% with a ballon-expandable valve. Analyzing a TAVI sample cohort (n=200), horizontal aorta (p<0.001, OR 11.7, 95% CI: [3.9:34.8]), defined as aortic angulation >48°(4), as well as the use of SEV (p<0.001, OR 12.8, 95% CI: [3.1:53.9]) were identified as a predisposing risk factor for TVEM. OR in SEV was severely increased when isolating the analysis for patients with horizontal aorta only (p=0.003, OR 23.75, 95% CI: [2.8:129]). No other predisposing risk factors were identified in this cohort. Out of 35 patients still alive, 6 patients were willing to participate in our imaging sub-study. CT exams were performed on average 47 months after TAVI (IQR 50 months [25%Q: 16.8, 75%Q: 72.8]). We detected no leaflet or stent thrombosis, yet CT identified pin protrusions in the aorta in 3 out of 6 patients. Conclusions TVEM is a rare complication of TAVI. TVEM was significantly associated to the use of self-expanding valves and the presence of horizontal aorta. CT did detect pin protrusions in several cases which could bear the possible risk of perforation but showed no signs of long-term damage. Funding Acknowledgement Type of funding sources: None. Representative CT images after TVEM

Background and methods Microaxial left ventricular assist devices are used increasingly for treating cardiogenic shock. We compared the short-term outcome of patients supported with different microaxial devices for cardiogenic shock. A retrospective propensity score-adjusted analysis was performed in cardiogenic shock patients treated with either the Impella CP (n = 64) or the Impella 5.0/5.5 (n = 62) at two tertiary cardiac care centers between 1/14 and 12/19. Results Patients in the Impella CP group were significantly older (69.6 ± 10.7 vs. 58.7 ± 11.9 years, p = .001), more likely in INTERMACS profile 1 (76.6% vs. 50%, p = .003) and post-C-reactive protein (CPR) (36% vs. 13%, p = .006). The median support time was 2.0 days [0.0, 5.3] in the CP group vs. 8.5 days [4.3, 15.8] in the 5.0/5.5 group (p < .001). The unadjusted 30-day survival was significantly higher in the Impella 5.0/5.5 group (58% vs. 36%, p = .021, odds ratio [OR] for 30-day survival on Impella 5.0/5.5 was 3.68 [95% confidence interval [CI]: [1.46–9.90]], p = .0072). After adjustment, the 30-day survival was similar for both devices (OR: 1.23, 95% CI: [0.34–4.18], p = .744). Lactate levels above 8 mmol/L and preoperative CPR were associated with a significant mortality increase in both cohorts (OR: 10.7, 95% CI: [3.45–47.34], p < .001; OR: 13.2, 95% CI: [4.28–57.89], p < .001, respectively). Conclusion Both Impella devices offer a similar effect with regard to survival in cardiogenic shock patients. Preoperative CPR or lactate levels exceeding 8 mmol/L immediately before implantation have a poor prognosis on Impella CP and Impella 5.0/5.5.

Microaxial LVADs are increasingly used for cardiogenic shock treatment. We compared the short-term outcome of patients supported with different microaxial devices for cardiogenic shock. A retrospective propensity score-adjusted analysis was performed in cardiogenic shock patients treated with either the Impella CP (n=64) or the Impella 5.0/5.5 (n=62) at two tertiary cardiac care centers between 1/14 and 12/19. Patients in the Impella CP group were significantly older (69.6±10.7 vs 58.7±11.9 years, p=0.001), more likely in an INTERMACS level 1 (76.6% vs 50%, p=0.003) and post CPR (36% vs 13%, p=0.006). The unadjusted 30-day survival was significantly higher in Impella 5.0/5.5 group (58% vs 36%, p=0.021, odds ratio (OR) for 30-day survival on Impella 5.0/5.5 was 3.68 (95% CI [1.46-9.90], p=0.0072). After adjustment, the 30-day survival was similar for both devices (OR 1.23, 95% CI [0.34-4.18], p=0.744). Lactate levels above 8 mmol/L and preoperative CPR were associated with a significant mortality increase in both cohorts (OR=10.7, 95% CI [3.45-47.34], p<0.001; OR=13.2, 95% CI [4.28-57.89], p<0.001, respectively). Both Impella devices offer a similar effect with regards to survival in cardiogenic shock patients. Preoperative CPR or lactate levels exceeding 8 mmol/L immediately before implantation have a poor prognosis on Impella CP and Impella 5.0/5.5.

AimsTo compare the outcomes of patients undergoing non-cardiac surgery (NCS) after PCI with either a drug-coated stent (DCS) or a bare-metal stent (BMS), followed by 1-month dual antiplatelet therapy and to explore the impact of the timing of NCS.Methods This is a subgroup analysis of the LEADERS FREE trial. The primary safety end point was a composite of cardiac death, myocardial infarction, or stent thrombosis, and the primary efficacy end point was clinically driven target lesion revascularization (TLR).ResultsOut of 2432 patients included in the LEADERS FREE trial, 278 (11.4%) underwent NCS within 1 year after PCI. Among NCS patients, the 1-year safety end point was numerically lower with DCS; however, this difference was not significant as compared to BMS (4.7% vs. 10.1%, HR: 0.459 [0.178–1.183], p = 0.099), clinically driven TLR was significantly lower after DCS (2.4% vs. 8.3%, HR: 0.281 [0.079—0.996], p = 0.036), and BARC 3–5 bleeding was similar with DCS vs. BMS (10.2% vs. 7.5%, p = 0.438). In patients treated with BMS, NCS within 3 months after PCI was associated with higher incidence of the safety end point than NCSs performed later: 14.9% vs. 4.4%, HR: 3.586 [1.012–12.709], p = 0.034. The timing of surgery had no impact on patients treated with DCS (4.7% vs. 4.7%, p = 0.947).Conclusions Among patients undergoing NCS after PCI, DCS-treated patients had a lower probability of clinically driven TLR compared with BMS. However, there was no significant difference in the occurrence of the primary composite safety end point or bleeding complications. Early NCS after BMS-PCI was associated with impaired safety, while the timing of NCS had no such influence after DCS implantation.Graphic abstract

COVID-19 pandemic is causing an unprecedented burden on healthcare resources and this includes treatment of heart failure and valvular heart diseases (VHD). Percutaneous procedures have broadened the number of patients with VHD who could be treated. However, COVID-19 pandemic has challenged their implementation. The risk of in-hospital infection, resources reallocation, reduced access to hospital caused a substantial delay of VHD treatment with an increased risk of clinical worsening and mortality. Now, the pandemic is not ended and subsequent waves are likely. Reorganization of our healthcare resources is needed, including a proper algorithm for patients’ prioritization, based on the severity of their valve disease, their life expectancy, complexity of the intervention, and the resources available. A wider use of telemedicine for patients’ selection and follow-up and any measurement that can shorten the duration of the hospital stay must be adopted. Patients’ and healthcare staff screening for COVID-19 and all needed procedures to prevent infection will continue to be mandatory. Percutaneous procedures, compared to surgery, are associated with a lower risk of infection and a lower need for in-hospital resources, including a shorter duration of hospital stay. This may favour their adoption when the risk of viral infection is high.