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Abstract Aims Achieving optimized guideline‐directed medical therapy (GDMT) is recommended prior to transcatheter mitral valve edge‐to‐edge repair (M‐TEER) for secondary mitral regurgitation (SMR). We aimed to propose and validate an easy‐to‐use score for assessing the quality of GDMT in patients with heart failure with reduced ejection fraction (HFrEF) undergoing M‐TEER. Methods and results Among the 1641 EuroSMR patients enrolled in the EuroSMR Registry who underwent M‐TEER, a total of 1072 patients [median age 74, interquartile range (IQR) 67–79 years, 29% female] had complete data on GDMT and a left ventricular ejection fraction ≤ 40% and were included in the current study. We proposed a GDMT score that considers the dosage levels of three medication classes (angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor‐neprilysin inhibitors, beta‐blockers, and mineralocorticoid receptor antagonists), with a maximum score of 12 points indicating optimal GDMT. The primary outcome was all‐cause mortality. The median GDMT score was 4 points (IQR 3–6). All three domains of the scoring system were associated with all‐cause mortality (P

Abstract Aims We aimed to conduct a clinical process cost analysis to evaluate all upcoming costs of mitral valve transcatheter edge-to-edge repair (M-TEER) treatment using the MitraClip and the PASCAL repair system. Methods First, we prospectively enrolled 107 M-TEER patients treated with either the PASCAL or MitraClip system and compared all upcoming costs during the M-TEER procedure and the associated in-hospital stay. Second, we retrospectively analysed 716 M-TEER procedures with regard to the occurrence of complications and their associated costs. All materials used in the catheterization laboratory for the procedures were evaluated. The cost analysis considered various expenses, such as general in-hospital costs, device costs, catheter laboratory and material costs. Results In the prospective study, 51 patients were treated using the PASCAL system, and 56 were treated using the MitraClip system. The two groups had comparable baseline characteristics and comorbidities. The total in-hospital costs were 25 414 (Interquartile range (IQR) 24 631, 27 697) € in the PASCAL group and 25 633 (IQR 24 752, 28 256) € in the MitraClip group (p = 0.515). The major cost driver was initial material expenditure, mostly triggered by device costs, which were similar to the PASCAL and MitraClip systems. Overall intensive care unit and general ward costs did not differ between the PASCAL and MitraClip groups. In the retrospective analysis, M-TEER-related complications were rare but were associated with higher costs, mainly due to prolonged hospitalisation. Conclusion The major cost driver of M-TEER was the material expenditure, which was mostly triggered by high device costs. The costs of treating patients were similar for the PASCAL and MitraClip systems. M-TEER-related complications are associated with higher costs, mainly due to prolonged hospitalisation. This analysis provides valuable insights into reducing expenses by modifying the process of M-TEER.

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

Background & Aims: PEDFIC 2, an ongoing, open-label, 72-week study, evaluates odevixibat, an ileal bile acid transporter inhibitor, in patients with progressive familial intrahepatic cholestasis. Methods: PEDFIC 2 enrolled and dosed 69 patients across two cohorts; all received odevixibat 120 μg/kg per day. Cohort 1 comprised children from PEDFIC 1, and cohort 2 comprised new patients (any age). We report data through 15 July 2020, with Week 24 of PEDFIC 2 the main time point analysed. This represents up to 48 weeks of cumulative exposure for patients treated with odevixibat from the 24-week PEDFIC 1 study (cohort 1A) and up to 24 weeks of treatment for those who initiated odevixibat in PEDFIC 2 (patients who received placebo in PEDFIC 1 [cohort 1B] or cohort 2 patients). Primary endpoints for this prespecified interim analysis were change from baseline to Weeks 22–24 in serum bile acids (sBAs) and proportion of positive pruritus assessments (≥1-point drop from PEDFIC 2 baseline in pruritus on a 0–4 scale or score ≤1) over the 24-week period. Safety monitoring included evaluating treatment-emergent adverse events (TEAEs). Results: In cohort 1A, mean change from PEDFIC 1 baseline to Weeks 22–24 of PEDFIC 2 in sBAs was -201 μmol/L (p

Background Neurologic events during primary stay in heart transplant (HTx) recipients may be associated with reduced outcome and survival, which we aim to explore with the current study. Methods and Results We screened and included all patients undergoing HTx in our center between September 2010 and December 2022 (n=268) and checked for the occurrence of neurologic events within their index stay. Neurologic events were defined as ischemic stroke, hemorrhage, hypoxic ischemic injury, or acute symptomatic neurologic dysfunction without central nervous system injury. The cohort was then divided into recipients with (n=33) and without (n=235) neurologic events after HTx. Using a multivariable Cox regression model, the association of neurologic events after HTx and survival was assessed. Recipients with neurologic events displayed a longer intensive care unit stay (30 versus 16 days; P=0.009), longer mechanical ventilation (192 versus 48 hours; P

Abstract Aim The quality of the donor heart is known to have a crucial effect on outcome after heart transplantation (HTx). Although leading to brain death in the end, the initial cause of death of the donor and its potential influences on organ quality are heterogeneous. However, it is still controversial to which extent the donor cause of death is associated with outcome or survival post‐HTx. Methods and results We included all patients undergoing HTx in our centre between September 2010 and June 2021 (n = 218). Recipients were divided in five groups related to their donor cause of death: intracerebral bleeding (‘ICB’, n = 95, 44%), traumatic brain injury (‘trauma’, n = 54, 25%), hypoxic brain damage (‘hypoxic’, n = 34, 16%), cerebrovascular (‘vascular’, n = 15, 7%), or other cause (n = 20, 9%). Baseline characteristics, perioperative parameters, and survival after 30 and 90 days as well as 5 years after transplantation were collected. Results Intracerebral bleeding in donors compared with traumatic brain injury is associated with higher probability of need for ECLS post‐HTx (35% vs. 19%, P = 0.04) and significantly reduced survival up to 5 years post‐HTx (i.e. 1 year survival: 61% vs. 95%, P

Abstract Aims Donor heart shortage leads to increasing use of left ventricular assist device (LVAD) as bridge‐to‐transplant or destination therapy. Prolonged LVAD support is associated with aortic valve insufficiency, representing a relevant clinical problem in LVAD patients. Nevertheless, the impact of LVAD support on inflammation, remodelling, and chondro‐osteogenic differentiation of the aortic valve is still not clearly understood. The aim of the study is to evaluate the impact of LVAD support on structural and molecular alterations of the aortic valve. Methods and results During heart transplantation, aortic valves of 63 heart failure patients without (n = 22) and with LVAD support (n = 41) were collected and used for analysis. Data on clinical course as well as echocardiographic data were analysed. Calcification and markers of remodelling, chondro‐osteogenic differentiation, and inflammation were evaluated by computed tomography, by mRNA analysis and by histology and immunohistochemistry. Expression of inflammation markers of the LVAD group was analysed with regard to levels of C‐reactive protein and driveline infections. Calcium accumulation and mRNA expression of determined markers were correlated with duration of LVAD support. Data were also analysed relating to aortic valve opening and aortic valve insufficiency. There was no difference in the frequency of cardiovascular risk factors or comorbidities between the patient groups. Expression of matrix metalloproteinase‐9 (P = 0.007), alpha‐smooth muscle actin (P = 0.045), and osteopontin (P = 0.003) were up‐regulated in aortic valves of LVAD patients. Histological appearance of the aortic valve was similar in patients with or without LVAD, and computed tomography‐based analysis not yet revealed significant difference in tissue calcification. Expression of interferon gamma (P = 0.004), interleukin‐1 beta (P

Abstract Aims Acute cellular rejection (ACR) following heart transplantation (HTX) is associated with long‐term graft loss and increased mortality. Disturbed mitochondrial bioenergetics have been identified as pathophysiological drivers in heart failure, but their role in ACR remains unclear. We aimed to prove functional disturbances of myocardial bioenergetics in human heart transplant recipients with mild ACR by assessing myocardial mitochondrial respiration using high‐resolution respirometry, digital image analysis of myocardial inflammatory cell infiltration, and clinical assessment of HTX patients. We hypothesized that (i) mild ACR is associated with impaired myocardial mitochondrial respiration and (ii) myocardial inflammation, systemic oxidative stress, and myocardial oedema relate to impaired mitochondrial respiration and myocardial dysfunction. Methods and results We classified 35 HTX recipients undergoing endomyocardial biopsy according International Society for Heart and Lung Transplantation criteria to have no (0R) or mild (1R) ACR. Additionally, we quantified immune cell infiltration by immunohistochemistry and digital image analysis. We analysed mitochondrial substrate utilization in myocardial fibres by high‐resolution respirometry and performed cardiovascular magnetic resonance (CMR). ACR (1R) was diagnosed in 12 patients (34%), while the remaining 23 patients revealed no signs of ACR (0R). Underlying cardiomyopathies (dilated cardiomyopathy 50% vs. 65%; P = 0.77), comorbidities (type 2 diabetes mellitus: 50% vs. 35%, P = 0.57; chronic kidney disease stage 5: 8% vs. 9%, P > 0.99; arterial hypertension: 59% vs. 30%, P = 0.35), medications (tacrolimus: 100% vs. 91%, P = 0.54; mycophenolate mofetil: 92% vs. 91%, P > 0.99; prednisolone: 92% vs. 96%, P > 0.99) and time post‐transplantation (21.5 ± 26.0 months vs. 29.4 ± 26.4 months, P = 0.40) were similar between groups. Mitochondrial respiration was reduced by 40% in ACR (1R) compared with ACR (0R) (77.8 ± 23.0 vs. 128.0 ± 33.0; P 14 CD3+‐lymphocytes/mm2 (100% sensitivity, 82% specificity; P

Abstract Aims This multicentre study investigated the association of periprocedural changes in the levels of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) with clinical outcomes after transcatheter edge‐to‐edge mitral valve repair (TMVR). Methods and results Patients were retrospectively analysed who underwent TMVR with the MitraClip system (Abbott Vascular, Santa Clara, CA, USA) and had available sequential NT‐proBNP testing at baseline and 2 months after TMVR. Periprocedural changes in NT‐proBNP following TMVR were assessed as the percent change in NT‐proBNP between baseline and the 2 month follow‐up, and the significant reduction in NT‐proBNP was defined as a decrease of >30% in the follow‐up NT‐proBNP compared with the pre‐procedural NT‐proBNP level. Primary outcome was defined as a composite outcome consisting of all‐cause mortality and hospitalization due to heart failure from 2 months to 2 years after TMVR. Additionally, we identified the cut‐off value of pre‐procedural NT‐proBNP to predict the composite outcome using a receiver operating characteristic analysis (cut‐off: 2485 pg/mL). Of 485 patients undergoing TMVR (age: 76.2 ± 9.2 years, female: 42.1%, secondary mitral regurgitation: 67.2%), 150 patients (30.9%) had the significant reduction in NT‐proBNP (>30%) following the procedure. Patients with the NT‐proBNP reduction had a lower incidence of the composite outcome, compared with those without the reduction in NT‐proBNP (31.4% vs. 40.2%; log‐rank P = 0.03). The significant reduction in NT‐proBNP was also associated with a lower risk of the composite outcome [adjusted hazard ratio (HR): 0.67; 95% confidence interval (CI): 0.45–0.97; P = 0.04], independently of pre‐procedural NT‐proBNP levels and other clinical parameters. The percent change in NT‐proBNP was associated with a linear trend of the incidence of the composite outcome (adjusted HR per 10% decrease: 0.96; 95% CI: 0.94–0.98; P 2485 pg/mL) was associated with the increased risk of the composite outcome (adjusted HR: 1.50; 95% CI: 1.03–2.17; P = 0.03); however, patients with a higher pre‐procedural NT‐proBNP who achieved the significant reduction in NT‐proBNP had a similar risk of the composite outcome to those with a lower pre‐procedural NT‐proBNP. Conclusions Changes in sequential NT‐proBNP measurements were associated with clinical outcomes within 2 years after TMVR. The assessment of NT‐proBNP dynamics may be valuable to assess the residual risk for patients undergoing TMVR and could assist with post‐procedural management after TMVR.

BackgroundThe deployment process of the largest self-expandable device (STHV-34) during transcatheter aortic valve implantation (TAVI) might be challenging due to stabilization issues. Whether the use of different TAVI-guidewires impact the procedural success and outcome is not well-known. Therefore, we sought to evaluate the impact of non-Lunderquist (NLu) vs. the Lunderquist (Lu) guidewires during TAVI using the STHV-34 on the procedural and 30-day outcomes.MethodsThe primary study endpoint was defined as the final implantation depth (ID) depending on the selected guidewire strategy. Key secondary endpoints included VARC-3-defined complications.ResultsThe study cohort included 398 patients of four tertiary care institutions, of whom 79.6% (317/398) had undergone TAVI using NLu and 20.4% (81/398) using Lu guidewires. Baseline characteristics did not substantially differ between NLu and Lu patients. The average ID was higher in the Lu cohort (NLu vs. Lu: −5.2 [−7.0–(−3.5)] vs. −4.5 [−6.0–(−3.0)]; p = 0.022*). The optimal ID was reached in 45.0% of patients according to former and only in 20.1% according to nowadays best practice recommendations. There was no impact of the guidewire use on the 30-day outcomes, including conduction disturbances and pacemaker need (NLu vs. Lu: 15.1 vs. 18.5%; p = 0.706).ConclusionThe use of the LunderquistTM guidewire was associated with a higher ID during TAVI with the STHV-34 without measurable benefits in the 30-day course concerning conduction disturbances and associated pacemaker need. Whether using different guidewires might impact the outcome in challenging anatomies should be further investigated in randomized studies under standardized conditions.

Abstract In-hospital cardiac arrest (IHCA) is associated with poor outcomes. There are currently no standards for cardiac arrest teams in terms of member composition and task allocation. Here we aimed to compare two different cardiac arrest team concepts to cover IHCA management in terms of survival and neurological outcomes. This prospective study enrolled 412 patients with IHCA from general medical wards. From May 2014 to April 2016, 228 patients were directly transferred to the intensive care unit (ICU) for ongoing resuscitation. In the ICU, resuscitation was extended to advanced cardiac life support (ACLS) (Load-and-Go [LaG] group). By May 2016, a dedicated cardiac arrest team provided by the ICU provided ACLS in the ward. After return of spontaneous circulation (ROSC), the patients (n = 184) were transferred to the ICU (Stay-and-Treat [SaT] group). Overall, baseline characteristics, aetiologies, and characteristics of cardiac arrest were similar between groups. The time to endotracheal intubation was longer in the LaG group than in the SaT group (6 [5, 8] min versus 4 [2, 5] min, p = 0.001). In the LaG group, 96% of the patients were transferred to the ICU regardless of ROSC achievement. In the SaT group, 83% of patients were transferred to the ICU (p = 0.001). Survival to discharge did not differ between the LaG (33%) and the SaT (35%) groups (p = 0.758). Ultimately, 22% of patients in the LaG group versus 21% in the SaT group were discharged with good neurological outcomes (p = 0.857). In conclusion, we demonstrated that the cardiac arrest team concepts for the management of IHCA did not differ in terms of survival and neurological outcomes. However, a dedicated (intensive care) cardiac arrest team could take some load off the ICU.

Abstract Aims Percutaneous left ventricular assist devices (pVADs) are used to haemodynamically stabilize patients with cardiogenic shock (CS) caused by acute myocardial infarction (AMI). One out of every two patients has a non‐ischaemic cause of CS, and these patients differ profoundly from patients with AMI‐related CS. We assessed the usefulness of pVAD support for patients with non‐ischaemic CS. Methods and results We analysed 106 patients with CS and Impella® support between 2015 and 2018. CS was non‐ischaemic in 36 patients and AMI‐related in 70 patients. Compared with the AMI group, those in the non‐ischaemic group were significantly younger [median age 62 (50.8, 70.8) years vs. 68 (58.0, 75.5) years, P = 0.007] and had more patients with severely reduced left ventricular function (94% vs. 79%, P = 0.035) and worse glomerular filtration rate [45 (27, 57) mL/min vs. 60 (44, 78) mL/min]. Propensity score matching yielded 31 patients with non‐ischaemic CS and 31 patients with AMI‐related CS, without a difference in baseline laboratory values or comorbidities. In both groups, pVAD support was performed along with haemodynamic stabilization, reduction of catecholamines and normalization of lactate levels. In 7 days, systolic blood pressure increased from 91 (80, 101) mmHg at baseline to 100 (100, 120) mmHg in the non‐ischaemic CS group (P = 0.001) and 89 (80, 100) mmHg at baseline to 112 (100, 128) mmHg in the AMI‐related CS group (P = 0.001). Moreover, in 7 days, the need of catecholamines (calculated as vasoactive‐inotropic score) decreased from 32.0 (11.1, 47.0) at baseline to 5.3 (0, 16.1) in the non‐ischaemic group (P = 0.001) and from 35.2 (18.11, 67.0) to zero (0, 0) in the AMI‐related CS group (P = 0.001). Lactate level decreased from 3.8 (2.8, 5.9) mmol/L at baseline to 1.0 (0.8, 2.1) mmol/L (P = 0.001) in the non‐ischaemic CS group and from 3.8 (2.6, 6.5) mmol/L to 1.2 (1.0, 2.0) mmol/L in the AMI‐related group (P = 0.001). In the non‐ischaemic CS group, eight patients (25.8%) were upgraded to veno‐arterial extracorporeal membrane oxygenation (VA‐ECMO) or long‐term mechanical circulatory support. Two of these upgraded patients received heart transplantation. In the AMI group, eight patients (25.8%) were upgraded to VA‐ECMO or long‐term mechanical circulatory support. Ninety‐day survival did not significantly differ between the groups (non‐ischaemic CS group 48.4%, AMI‐related CS group 45.2%, P = 0.799). Conclusions pVAD support is useful for haemodynamic stabilization of patients with non‐ischaemic CS and is valuable as a bridge to patients' recovery or long‐term left ventricular support and heart transplantation.

Residual and recurrent tricuspid regurgitation may occur frequently after surgical tricuspid valve repair. However, reoperation for tricuspid regurgitation is rare, although many patients are again highly symptomatic. Tricuspid transcatheter edge-to-edge repair (TEER) is a promising therapy for severe tricuspid regurgitation. Herein, we report a 77-year-old woman with recurrent symptomatic massive tricuspid regurgitation 2 years after sutured annuloplasty of the tricuspid valve. TEER was successfully performed using the TriClip® device and tricuspid regurgitation was reduced to a mild degree. In conclusion, tricuspid TEER is feasible following surgical suture annuloplasty. TEER is an alternative option for patients with a failed previous annuloplasty repair for tricuspid regurgitation to undergo a less invasive treatment rather than a potentially higher-risk reoperation.

Myat Soe Thet et al. published a letter [...]

BackgroundTranscatheter tricuspid valve repair (TTVr) is routinely performed under general anesthesia (GA). This study aimed to investigate whether TTVr procedures can be performed effectively and safely without GA but using deep sedation (DS).MethodsWe performed a retrospective analysis of 104 patients from three centers who underwent TTVr between 2020 and 2021. The primary performance endpoints were technical success and severity of TR assessed at the time of discharge. The safety outcome was a composite of in-hospital complications, including occurrence of death, conversion to surgery, major adverse cardiac and cerebrovascular events, major vascular complications, or occurrence of pneumonia.ResultsSixty-four procedures were performed in GA and 40 procedures were performed in DS. The groups did not differ in age, EuroScore II, TR severity, ventricular function, or hemodynamic parameters. Technical success was achieved in 92.5% of the patients in the DS group and in 93.6% of the patients in the GA group (p = 0.805). In none of the patients intraprocedural conversion from DS to GA was required. There was no difference in total duration of the procedure, and number of devices implanted. The degree of TR was ≤2+ in 77.5% of the patients in the DS group and in 74.2% of the patients in the GA group (p = 0.705). The composite safety endpoint did not differ between the groups (2.5 vs. 6.3%, p = 0.384). The total duration of hospital stay was shorter in patients who underwent TTVr in DS compared to those who underwent TTVr in GA (6 [5, 9] days vs. 8 [6, 11] days; p = 0.011).ConclusionPerforming TTVr in DS was effective with similar procedural results, and was safe with similar low complication rates compared to GA.

BackgroundThe implantation depth (ID) is a critical condition for optimal hemodynamic and clinical outcomes in transcatheter aortic valve replacement (TAVR). The recently recommended cusp-overlap technique (COT) offers optimized fluoroscopic projections facilitating a precise ID. This single-center observational study aimed to investigate short-term clinical performance, safety, and efficacy outcomes in patients undergoing TAVR with self-expandable prostheses and application of COT in a real-world setting.Materials and methodsFrom September 2020 to April 2021, a total of 170 patients underwent TAVR with self-expandable devices and the application of COT, while 589 patients were treated from January 2016 to August 2020 with a conventional three-cusp coplanar view approach. The final ID and 30-day outcomes were compared after 1:1 propensity score matching, resulting in 150 patients in both cohorts.ResultsThe mean ID was significantly reduced in the COT cohort (−4.2 ± 2.7 vs. −4.9 ± 2.3 mm; p = 0.007) with an improvement of ID symmetry of less than 2 mm difference below the annular plane (47.3 vs. 57.3%; p = 0.083). The rate of new permanent pacemaker implantation (PPI) following TAVR was effectively reduced (8.0 vs. 16.8%; p = 0.028). While the fluoroscopy time decreased (18.4 ± 7.6 vs. 19.8 ± 7.6 min; p = 0.023), the dose area product increased in the COT group (4951 ± 3662 vs. 3875 ± 2775 Gy × cm2; p = 0.005). Patients implanted with COT had a shorter length of in-hospital stay (8.4 ± 4.0 vs. 10.3 ± 6.7 days; p = 0.007).ConclusionTranscatheter aortic valve replacement using the cusp-overlap deployment technique is associated with an optimized implantation depth, leading to fewer permanent conduction disturbances. However, our in-depth analysis showed for the first time an increase of radiation dose due to extreme angulations of the gantry to obtain the cusp-overlap view.

Abstract Aims Percutaneous mitral valve repair (PMVR) has emerged as standard treatment in selected patients with clinically relevant mitral regurgitation (MR) and increased surgical risk. We aimed to evaluate the safety and clinical outcomes in nonagenarians undergoing PMVR. Methods and results Altogether, 493 patients with severe MR who were treated with PMVR were included in this open‐label prospective study and followed up for 2 years. We treated 25 patients with PMVR aged 90 years or above, 185 patients aged 80–89 years, and 283 patients aged

Aims: Identifying patients who may benefit from mechanical circulatory support (MCS) after out-of-hospital cardiac arrest (OHCA) and return of spontaneous circulation (ROSC) remains challenging; thus, a search for helpful biomarkers is warranted. We aimed to evaluate phosphate and lactate levels on admission regarding their associations with survival with and without MCS. Methods: In 224 OHCA patients who achieved ROSC, the initial phosphate and lactate levels were investigated to discriminate in-hospital mortality by receiver operating characteristic (ROC) curves. According to the Youden Index (YI) from the respective ROC, the groups were risk stratified by both biomarkers, and 30-day mortality was analyzed in patients with and without MCS. Results: Within the entire collective, MCS was not associated with a better chance of survival. Both phosphate and lactate level elevations showed good yet comparable discriminations to predict mortality (areas under the curve: 0.80 vs. 0.79, p = 0.74). In patients with initial phosphate values > 2.2 mmol/L (>YI), 30-day mortality within the MCS cohort was lower (HR 2.3, 95% CI: 1.4–3.7; p = 0.0037). In patients with lower phosphate levels and groups stratified by lactate, 30-day mortality was similar in patients with and without MCS. Conclusions: We found a significant association between survival and MCS therapy in patients with phosphate levels above 2.2 mmol/L (Youden Index), and a similar discrimination of patient overall survival by lactate and phosphate. Prospective studies should assess the possible independent prognostic value of phosphate and its clearance for MCS efficiency.

Purpose: Although a moderate proportion of cardiac arrest (CA) patients achieve a return of spontaneous circulation (ROSC), few survive to discharge, mostly with poor neurological development. As serum phosphate levels were described as elevated after cardiopulmonary resuscitation (CPR), we asked whether these elevations would predict a higher risk of mortality and impaired neurological outcome in CA patients following ROSC. Methods: Initial serum phosphate levels, survival, and neurologic status at discharge of 488 non-traumatic CA patients treated at a single German hospital after achieving ROSC were analyzed. The cut-off value of phosphate for mortality prediction was determined using the receiver operator characteristic (ROC) curve, and patients were divided accordingly for comparison. Results were validated by analyzing phosphate levels in a multi-centric cohort containing 3299 CA patients from the eICU database of the United States. Results: In the German cohort, ROC analysis showed a 90% specificity for phosphate levels >2.7 mmol/L to predict mortality (AUC: 0.76, p < 0.0001), and phosphate level elevations were associated with higher in-hospital mortality (crude odds ratio 3.04, 95% CI 2.32 to 4.08). Patients with initial phosphate levels >2.7 mmol/L had significantly higher mortality in both analyzed collectives (p < 0.0001). Similarly, patients from the German cohort who initially had higher phosphate levels also showed a higher proportion of impaired neurological status at discharge and morphological signs of brain injury. Conclusions: In CA patients following ROSC, initial serum phosphate levels >2.7 mmol/L predict higher mortality and impaired neurological outcome. Our data suggests that phosphate determination might improve the preciseness of the overall and neurologic prognostication in patients after CPR following ROSC.

Background Optimizing risk stratification in patients undergoing transcatheter mitral valve repair is an ongoing challenge. The Mitral Regurgitation International Database (MIDA) score represents a user‐friendly mortality risk stratification tool that is validated on a large‐scale registry of patients with degenerative mitral regurgitation (MR). We here assessed the potential benefit of the MIDA risk score for patients with functional or degenerative MR undergoing transcatheter mitral valve repair. Methods and Results In total, 680 patients undergoing MitraClip implantation were stratified according to MIDA score tertiles into a low (0–7), intermediate (8–9), and a high (10–12) MIDA score group. MR was assessed in follow‐up echocardiograms in 416 patients at 323±169 days after transcatheter mitral valve repair. During 2‐year follow‐up, 8.2% (15/182) of patients with low, 21.3% (64/300) with intermediate, and 26.3% (52/198) with high MIDA score died (log‐rank test P

Background: In secondary MR, data on left ventricular (LV) remodeling after MitraClip procedure are rare, even this information may impact patient selection. This study investigated changes in LV structure and function by cardiovascular magnetic resonance (CMR) following MitraClip implantation for secondary mitral regurgitation (MR) in order to assess extent and predictors of LV reverse remodeling (LVRR). Methods and Results: Twenty-nine patients underwent CMR imaging prior to and six months after MitraClip procedure. LVRR was defined by a decrease of LV end-diastolic volume index (LVEDVi) > 15% compared to baseline. According to the definition of LVRR, 34% of patients displayed LVRR at follow-up CMR. Baseline LV stroke volume index (LVSVi), LV ejection fraction (LVEF), LV circumferential strain and MR volume at baseline were predictors of LVRR at follow-up. At second CMR, we detected an improvement in hemodynamic status as illustrated by an increase in effective LVSVi (28 ± 8 ml/m2 vs. 33 ± 8 ml/m2; p = 0.053) and cardiac index (2.0 ± 0.5 vs. 2.3 ± 0.5 l/min; p = 0.016), while LVEF and LV strain parameters did not change (p > 0.05). Improvements in effective LVSVi were associated with the decrease of MR volume (r = 0.509; p = 0.018) and MR fraction (r = 0.629; p = 0.002) by MitraClip. Conclusions: Together, MitraClip implantation is associated with LVRR in one third of patients. Baseline LV function and magnitude of MR are important predictors of LVRR. Improvement of hemodynamic status may be assessed by effective stroke volume index and correlates with the reduction of MR by MitraClip implantation, rather than an increase in LV contractility.

Prolonged treatment of organ donors in the intensive care unit (ICU) may be associated with complications influencing the outcome after heart transplantation (HTx). We therefore aim to explore the potential impact of the donor length of stay (LOS) in the ICU on outcomes in our cohort. We included all patients undergoing HTx in our center between September 2010 and April 2022 (n = 241). Recipients were divided around the median into three groups regarding their donor LOS in the ICU: 0 to 3 days (≤50th percentile, n = 92), 4 to 7 days (50th–75th percentile, n = 80), and ≥8 days (≥75th percentile, n = 69). Donor LOS in the ICU ranged between 0 and 155 days (median 4, IQR 3–8 days). No association between the LOS in the ICU and survival after HTx was observed (AUC for overall survival 0.514). Neither the Kaplan–Meier survival analysis up to 5 years after HTx (Log-Rank p = 0.789) nor group comparisons showed significant differences. Baseline recipient characteristics were comparable between the groups, while the donor baselines differed in some parameters, such as less cardiopulmonary resuscitation prior to HTx in those with a prolonged LOS. However, regarding the recipients’ peri- and postoperative parameters, the groups did not differ in all of the assessed parameters. Thus, in this retrospective analysis, although the donors differed in baseline parameters, the donor LOS in the ICU was not associated with altered recipient survival or outcome after HTx.

Due to shortages of medical resources during the Coronavirus Disease 2019 (COVID-19) pandemic, an allocation algorithm for Transcatheter Aortic Valve Replacement (TAVR) was established. We investigated the impact on patient selection and procedural results. In total, 456 TAVR patients before (pre-COVID-19 group) and 456 TAVR patients after (COVID-19 group) the implementation of our allocation algorithm were compared. Concerning patient characteristics, the COVID-19 group revealed a higher rate of cardiac decompensations/cardiogenic shocks (10.5% vs. 1.3%; p < 0.001), severe angina pectoris (Canadian Cardiovascular Society (CCS) II, III and IV: 18.7% vs. 11.8%; p = 0.004), troponin elevation (>14 ng/L: 84.9% vs. 77%; p = 0.003) and reduced left ventricular ejection fraction (LVEF) (p = 0.006). Referring to procedural characteristics, more predilatations (46.3% vs. 35.1%; p = 0.001) and a longer procedural time (80.2 min (+/−29.4) vs. 66.9 min (+/−17.5); p < 0.001) were observed. The success rate was evenly high; no differences in safety parameters were reported. Examining the utilization of hospital resources, the COVID-19 group showed a shorter in-hospital stay (8.4 days (+/−5.9) vs. 9.5 days (+/−9.33); p = 0.041) and fewer TAVR patients were treated per month (39 (+/−4.55) vs. 46.11 (+/−7.57); p = 0.03). Our allocation algorithm supported prioritization of sicker patients with similar efficient and safe TAVR procedures. In-hospital stay could be shortened.

AimsTo evaluate whether CMR-derived RV assessment can facilitate risk stratification among patients undergoing transcatheter mitral valve repair (TMVR).BackgroundIn patients undergoing TMVR, only limited data exist regarding the role of RV function. Previous studies assessed the impact of pre-procedural RV dysfunction stating that RV failure may be associated with increased cardiovascular mortality after the procedure.MethodsSixty-one patients underwent CMR, echocardiography and right heart catheterization prior TMVR. All-cause mortality and heart failure hospitalizations were assessed during 2-year follow-up.ResultsAccording to RV ejection fraction (RVEF) ConclusionIn patients undergoing TMVR, pre-existing RV dysfunction and RV dilatation are associated with reduced survival, in progressive additive fashion. The assessment of RV volumes and function by CMR may aid in risk stratification prior TMVR in these high-risk patients.

Objectives The aim of this study was to investigate the impact of acute left ventricular unloading by percutaneous left ventricular assist device on pulmonary congestion and pneumonia in patients with cardiogenic shock (CS).Methods In this retrospective study, we analysed patients with CS who received the Impella percutaneous left ventricular assist device (n=50) compared with those who received intra-aortic balloon pump (IABP) support (n=50). Pulmonary congestion was longitudinally assessed while on support by calculating characteristic findings on the chest X-ray using the Halperin score. The rate of pneumonia and early mortality were assessed as a secondary endpoint.Results The groups (Impella vs IABP) did not differ in terms of age, Sequential Organ Failure Assessment (SOFA) score, Acute Physiology, Chronic Health Evaluation (APACHE) II score or serum lactate levels. Pulmonary congestion decreased in patient treated with Impella at each time point postimplantation. No change in congestion status was observed in patients supported with IABP. Multivariate analysis indicated Impella support as an independent predictor for pulmonary decongestion (OR 4.06, 95% CI 1.15 to 14.35, p=0.030). The rate of early pneumonia was lower in the Impella group compared with the IABP group (54% vs 74%, p=0.037). Failure of pulmonary decongestion during mechanical circulatory support independently predicted early pneumonia (OR 0.28, 95% CI 0.12 to 0.70, p=0.006).Conclusion Pulmonary decongestion may facilitate treatment of pneumonia in patients with CS. Left ventricular unloading by Impella device might support pulmonary decongestion, although a larger prospective trial in this patient population is required.

Heart failure: Energy metabolism reflects cardiac function The capacity of mitochondria in heart muscle cells to use oxygen to produce energy correlates with cardiac function. Julia Szendroedi at Heinrich-Heine University, Düsseldorf, Germany, and colleagues have established a technique to reliably evaluate mitochondrial energy metabolism in patients with or recovering from heart failure. They showed that the mitochondrial oxidative capacity of cells in the lower heart chambers (ventricles) was significantly higher than in the upper heart chambers (atria). Moreover, they found that mitochondrial oxidative capacity was reduced by 44% in heart muscle biopsies from patients with heart failure compared with biopsies from heart transplant recipients with normal ventricular function. Stimulating the respiration rate of mitochondria in ventricular heart cells could be a promising strategy for improving cardiac function.

Ageing causes an inability to replace damaged tissue. Here, the authors perform proteomics analyses of human haematopoietic stem cells and other cells in the bone marrow niche at different ages and show changes in central carbon metabolism, reduced bone marrow niche function, and enhanced myeloid differentiation.

Endothelial microparticles (EMPs) are markers of endothelial injury and activation. The role of EMPs in arterial hypertension is not well understood and EMPs are increased both in arterial hypertension and coronary artery disease (CAD). The data presented here show EMPs as defined by CD31+/41−, CD62e+, and CD144+ surface markers and vascular hemodynamic parameters including office and central blood pressure, heart rate, aortic augmentation index, pulse wave velocity, flow-mediated dilation, nitroglycerin-mediated dilation, brachial artery diameter, hyperemic wall shear stress, and laser Doppler perfusion of the cutaneous microcirculation of normotensives and hypertensives with and without CAD.

Abstract Background While most patients recover from suspected acute myocarditis (sAMC) some develop progressive disease with 5-year mortality up to 20%. Recently, parametric Cardiovascular Magnetic Resonance (CMR) approaches, quantifying native T1 and T2 relaxation time, have demonstrated the ability to increase diagnostic accuracy. However, prognostic implications of T2 values in this cohort are unknown. The purpose of the study was to investigate the prognostic relevance of elevated CMR T2 values in patients with sAMC. Methods and Results We carried out a prospective study in 46 patients with sAMC defined by current ESC recommendations. A combined endpoint was defined by the occurrence of at least one major adverse cardiac event (MACE) and hospitalisation for heart failure. Event rate was 24% (n = 11) for 1-year-MACE and hospitalisation. A follow-up after 11 ± 7 months was performed in 98% of the patients. Global T2 values were significantly increased at acute stage of disease compared to controls and decreased over time. During acute disease, elevated global T2 time (odds ratio 6.3, p 80 ms (odds ratio 4.9, p

The safety and efficacy of deep sedation (DS) in MitraClip® procedures have been shown previously. However, clinical experience demonstrates that in some patients DS is difficult to achieve. We hypothesize that some patient characteristics can predict difficult DS.We prospectively analysed 69 patients undergoing MitraClip® procedures using DS. Application of DS was graded as simple (group 1) or difficult (group 2) depending on a cumulative score based on one point for each of the following criteria: decrease in oxygen saturation, retention of carbon dioxide, disruptive body movements, and the need for catecholamines. Patients with one point or less were classified as group 1, and patients with two or more points were classified as group 2.In 58 of 69 patients (84.1%), the performance of DS was simple, while in 11 patients (15.9%), DS was difficult to achieve. Patients with difficult DS were characterized by a higher body mass index (33.7 ± 6.0 kg/m2 vs. 26.1 ± 4.1; p = 0.001), younger age (67 ± 13 years vs. 75 ± 13 years; p = 0.044), and reduced left ventricular ejection fraction (36% ± 10 vs. 45% ± 14; p = 0.051) and presented more often with an obstructive sleep apnoea syndrome (6.9% vs. 45.5%; p = 0.003). In the multivariate analysis, body mass index was an independent predictor of difficult DS. Using a body mass index of 31 kg/m2 as a cut-off value, the sensitivity of predicting difficult DS was 73%, and the specificity was 88%. Using a body mass index of 35 kg/m2 as a cut-off value, the specificity increased to 97%, with a sensitivity of 36%.In patients with a higher body mass index who undergo MitraClip® procedures, DS might be difficult to perform.

This essay traces a movement in New York State in the late 19th and early 20th centuries to protect depositors in small, private banks. These depositors were often located in immigrant communities that did not possess the local level of capital to support a national or state-chartered bank. Small private banks, the only entities that often served certain poor areas, were less regulated than state-chartered or national banks, especially with regard to capital levels and quality of assets. The fact that bank managers possessed the ability and incentives to assume additional risk exposed depositors in these small private banks to an increased danger of moral hazard. implicitly recognizing this risk, state officials in New York after the Panic of 1893 began a movement that spanned three decades to reduce the incentives for moral hazard and increase the protection for depositors in these immigrant communities.

Circulating microparticles (MPs) derived from endothelial cells and blood cells bear procoagulant activity and promote thrombin generation. Thrombin exerts proinflammatory effects mediating the progression of atherosclerosis. Aortic valve stenosis may represent an atherosclerosis-like process involving both the aortic valve and the vascular system. The aim of this study was to investigate whether MP-induced thrombin generation is related to coronary atherosclerosis and aortic valve calcification.In a cross-sectional study of 55 patients with severe aortic valve stenosis, we assessed the coronary calcification score (CAC) as indicator of total coronary atherosclerosis burden, and aortic valve calcification (AVC) by computed tomography. Thrombin-antithrombin complex (TATc) levels were measured as a marker for thrombin formation. Circulating MPs were characterized by flow cytometry according to the expression of established surface antigens and by measuring MP-induced thrombin generation.Patients with CAC score below the median were classified as patients with low CAC, patients with CAC Score above the median as high CAC. In patients with high CAC compared to patients with low CAC we detected higher levels of TATc, platelet-derived MPs (PMPs), endothelial-derived MPs (EMPs) and MP-induced thrombin generation. Increased level of PMPs and MP-induced thrombin generation were independent predictors for the severity of CAC. In contrast, AVC Score did not differ between patients with high and low CAC and did neither correlate with MPs levels nor with MP-induced thrombin generation.In patients with severe aortic valve stenosis MP-induced thrombin generation was independently associated with the severity of CAC but not AVC indicating different pathomechanisms involved in coronary artery and aortic valve calcification.

Preprocedural manual multi-slice-CT-segmentation tools (MSCT-ST) define the gold standard for planning transcatheter aortic valve replacement (TAVR). They are able to predict the perpendicular line of the aortic annulus (PPL) and to indicate the corresponding C-arm angulation (CAA). Fully automated planning-tools and their clinical relevance have not been systematically evaluated in a real world setting so far.The study population consists of an all-comers cohort of 160 consecutive TAVR patients with a drop out of 35 patients for technical and anatomical reasons. 125 TAVR patients underwent preprocedural analysis by manual (M-MSCT) and fully automated MSCT-ST (A-MSCT). Method-comparison was performed for 105 patients (Cohort A). In Cohort A, CAA was defined for each patient, and accordance within 10° between M-MSCT and A-MSCT was considered adequate for concept-proof (95% in LAO/RAO; 94% in CRAN/CAUD). Intraprocedural CAA was defined by repetitive angiograms without utilizing the preprocedural measurements. In Cohort B, intraprocedural CAA was established with the use of A-MSCT (20 patients). Using preprocedural A-MSCT to indicate the corresponding CAA, the levels of contrast medium (ml) and radiation exposure (cine runs) were reduced in Cohort B compared to Cohort A significantly (23.3±10.3 vs. 35.3 ±21.1 ml, p = 0.02; 1.6±0.7 vs. 2.4±1.4 cine runs; p = 0.02) and trends towards more safety in valve-positioning could be demonstrated.A-MSCT-analysis provides precise preprocedural information on CAA for optimal visualization of the aortic annulus compared to the M-MSCT gold standard. Intraprocedural application of this information during TAVR significantly reduces the levels of contrast and radiation exposure.ClinicalTrials.gov NCT01805739.

Stent implantation into atherosclerotic coronary vessels impacts on downstream microvascular function and induces the release of particulate debris and soluble substances, which differs qualitatively and quantitatively between native right coronary arteries (RCAs) and saphenous vein grafts on right coronary arteries (SVG-RCAs). We have now quantified the release of microparticles (MPs) during stent implantation into stable atherosclerotic lesions and compared the release between RCAs and SVG-RCAs.In symptomatic, male patients with stable angina and a stenosis in their RCA or SVG-RCA, respectively (n = 14/14), plaque volume and composition were analyzed using intravascular ultrasound before stent implantation. Coronary aspirate was retrieved during stent implantation with a distal occlusion/aspiration device and divided into particulate debris and plasma. Particulate debris was weighed. Platelet-derived MPs (PMPs) were distinguished by flow cytometry as CD41+, endothelium-derived MPs (EMPs) as CD144+, CD62E+ and CD31+/CD41-, leukocyte-derived MPs as CD45+, and erythrocyte-derived MPs as CD235+.In patients with comparable plaque volume and composition in RCAs and SVG-RCAs, intracoronary PMPs and EMPs were increased after stent implantation into their RCAs and SVG-RCAs (CD41+: 2729.6 ± 645.6 vs. 4208.7 ± 679.4 and 2355.9 ± 503.9 vs. 3285.8 ± 733.2 nr/µL; CD144+: 451.5 ± 87.9 vs. 861.7 ± 147.0 and 444.6 ± 74.8 vs. 726.5 ± 136.4 nr/µL; CD62E+: 1404.1 ± 247.7 vs. 1844.3 ± 378.6 and 1084.6 ± 211.0 vs. 1783.8 ± 384.3 nr/µL, P < 0.05), but not different between RCAs and SVG-RCAs.Stenting in stable atherosclerotic lesions is associated with a substantial release not only of PMPs, but also of EMPs in RCAs and SVG-RCAs. Their release does not differ between RCAs and SVG-RCAs.ClinicalTrials.gov NCT01430884.

Background Research on mesenchymal stromal cells has created high expectations for a variety of therapeutic applications. Extensive propagation to yield enough mesenchymal stromal cells for therapy may result in replicative senescence and thus hamper long-term functionality in vivo. Highly variable proliferation rates of mesenchymal stromal cells in the course of long-term expansions under varying culture conditions may already indicate different propensity for cellular senescence. We hypothesized that senescence-associated regulated genes differ in mesenchymal stromal cells propagated under different culture conditions.Design and Methods Human bone marrow-derived mesenchymal stromal cells were cultured either by serial passaging or by a two-step protocol in three different growth conditions. Culture media were supplemented with either fetal bovine serum in varying concentrations or pooled human platelet lysate.Results All mesenchymal stromal cell preparations revealed significant gene expression changes upon long-term culture. Especially genes involved in cell differentiation, apoptosis and cell death were up-regulated, whereas genes involved in mitosis and proliferation were down-regulated. Furthermore, overlapping senescence-associated gene expression changes were found in all mesenchymal stromal cell preparations.Conclusions Long-term cell growth induced similar gene expression changes in mesenchymal stromal cells independently of isolation and expansion conditions. In advance of therapeutic application, this panel of genes might offer a feasible approach to assessing mesenchymal stromal cell quality with regard to the state of replicative senescence.

The regenerative potential diminishes with age and this has been ascribed to functional impairments of adult stem cells. Cells in culture undergo senescence after a certain number of cell divisions whereby the cells enlarge and finally stop proliferation. This observation of replicative senescence has been extrapolated to somatic stem cells in vivo and might reflect the aging process of the whole organism. In this study we have analyzed the effect of aging on gene expression profiles of human mesenchymal stromal cells (MSC) and human hematopoietic progenitor cells (HPC). MSC were isolated from bone marrow of donors between 21 and 92 years old. 67 genes were age-induced and 60 were age-repressed. HPC were isolated from cord blood or from mobilized peripheral blood of donors between 27 and 73 years and 432 genes were age-induced and 495 were age-repressed. The overlap of age-associated differential gene expression in HPC and MSC was moderate. However, it was striking that several age-related gene expression changes in both MSC and HPC were also differentially expressed upon replicative senescence of MSC in vitro. Especially genes involved in genomic integrity and regulation of transcription were age-repressed. Although telomerase activity and telomere length varied in HPC particularly from older donors, an age-dependent decline was not significant arguing against telomere exhaustion as being causal for the aging phenotype. These studies have demonstrated that aging causes gene expression changes in human MSC and HPC that vary between the two different cell types. Changes upon aging of MSC and HPC are related to those of replicative senescence of MSC in vitro and this indicates that our stem and progenitor cells undergo a similar process also in vivo.

Mesenchymal stem cells (MSC) comprise a promising tool for cellular therapy. These cells are usually culture expanded prior to their application. However, a precise molecular definition of MSC and the sequel of long-term in vitro culture are yet unknown. In this study, we have addressed the impact of replicative senescence on human MSC preparations. Within 43 to 77 days of cultivation (7 to 12 passages), MSC demonstrated morphological abnormalities, enlargement, attenuated expression of specific surface markers, and ultimately proliferation arrest. Adipogenic differentiation potential decreased whereas the propensity for osteogenic differentiation increased. mRNA expression profiling revealed a consistent pattern of alterations in the global gene expression signature of MSC at different passages. These changes are not restricted to later passages, but are continuously acquired with increasing passages. Genes involved in cell cycle, DNA replication and DNA repair are significantly down-regulated in late passages. Genes from chromosome 4q21 were over-represented among differentially regulated transcripts. Differential expression of 10 genes has been verified in independent donor samples as well as in MSC that were isolated under different culture conditions. Furthermore, miRNA expression profiling revealed an up-regulation of hsa-mir-371, hsa-mir-369-5P, hsa-mir-29c, hsa-mir-499 and hsa-let-7f upon in vitro propagation. Our studies indicate that replicative senescence of MSC preparations is a continuous process starting from the first passage onwards. This process includes far reaching alterations in phenotype, differentiation potential, global gene expression patterns, and miRNA profiles that need to be considered for therapeutic application of MSC preparations.