Fully magnetically centrifugal left ventricular assist device and long-term outcomes: the ELEVATE registry.

BACKGROUND AND AIMS: HeartMate 3 (HM3) is a fully magnetically levitated continuous flow left ventricular assist device, which received CE marking in 2015. The ELEVATE Registry was initiated to collect real-world outcomes in patients treated with HM3 post-CE Mark approval. METHODS: A total of 540 subjects implanted at 26 centres between March 2015 and February 2017 were included in this registry. Of these, 463 received the device as a primary implant (primary implant cohort, PIC), 19 as a pump exchange (pump exchange cohort), and in 58 patients, only anonymized survival data were collected (anonymized cohort, AC). Patients in the PIC contributed to the baseline demographics, survival, adverse events, quality of life (QoL) (EuroQoL-5 Dimensions-5 Levels visual analogue scale), and functional capacity (6 min walk distance) assessments, while patients in the AC contributed only to survival. RESULTS: Primary implant cohort patients had a mean age of 56 years and were predominantly male (89%) with 48% ischaemic aetiology. The majority of subjects was designated bridge to transplant (66%) and had INTERMACS Profiles 1-3 (70%). At baseline, the subjects had poor functional capacity (104 ± 140 m) and impaired QoL (35 ± 19 points). The overall survival rate of the PIC was 63.3% and survival free of stroke was 58.1% at 5 years. Significant improvements in functional capacity and QoL were observed and maintained for 5 years (301 ± 131 m and 64 ± 20 points, respectively). CONCLUSIONS: Real-world data from the ELEVATE registry demonstrate an overall survival rate for primary implants of 63.3%. In the PIC, reductions in adverse events for patients in the extended follow-up and improved QoL and functional capacity were observed at 5 years in this patient population with advanced heart failure.

Molecular Mechanisms of Diaphragm Myopathy in Humans With Severe Heart Failure.

[Figure: see text].

Secondary analysis of potential associations between oral health and infection-related parameters in patients with severe heart failure-results of a German cohort.

OBJECTIVES: Aim of this retrospective cohort study was to evaluate whether oral health parameters would be associated with infection-related parameters and overall survival of patients with severe heart failure (HF). METHODS: Patients with severe HF, heart transplantation (HTx) and left-ventricular assist device (LVAD), which underwent a full oral examination between 2017 and 2018 were included. Infection-related and survival data were assessed from the patient´s medical records. The oral examination included: remaining teeth, caries and periodontal condition, including periodontal probing depth (PPD), clinical attachment loss (CAL), bleeding on probing (BOP), and diagnosis (staging/grading). In addition, the periodontal inflamed surface area (PISA) was determined. Statistical analysis included Chi-square, Fisher´s exact and Mann-Whitney-U test, as well as a logistic regression, considering age, gender, body-mass-index (BMI), diabetes and several oral health parameters with regard to overall survival and infections at heart/driveline. RESULTS: 329 patients (HTx: 34%, LVAD: 38.9%, HF: 27.1%), were included. Patients had on average 18.96 ± 8.90 remaining teeth, whereby the majority had a periodontitis stage III or IV (88.7%) and a grade B (80.5%). Higher BOP was associated with infections at heart/driveline (p = 0.04) and outside the heart (p < 0.01) during follow-up. Increased PISA was significantly associated with bacterial infections outside the heart (p < 0.01) and sepsis (p = 0.02). Only BMI of 25 or higher correlated with an increased risk of infections at heart/driveline in regression analysis (OR 3.063, CI95 1.158-8.101, p = 0.02), while no associations between oral health parameters and infections at heart/driveline or overall survival were confirmed. CONCLUSIONS: In patients with severe HF, periodontal inflammation might be associated with infection-related parameters. Improved dental care, especially including periodontal therapy and maintenance might be favourable to support prevention of infections in patients with severe HF.

Is implantable cardioverter defibrillator surgery in patients with an implanted left ventricular assist device safe under uninterrupted oral anticoagulation?

BACKGROUND: Implantable cardioverter-defibrillator (ICD) surgery in patients with implanted left ventricular assist devices (LVAD) is associated with an increased risk of bleeding complications because of the need to ensure that these patients are adequately anticoagulated. Our study aimed to evaluate the safety of our new strategy of uninterrupted oral anticoagulation compared to heparin-bridging during the surgical interval. METHODS: Between January 2009 and January 2020, 116 patients with LVAD underwent ICD surgery. Since January 2015, 60 patients were operated under continued sufficient oral anticoagulation with a vitamin k antagonist (VKA group). Fifty-six patients underwent a heparin-bridging regimen (heparin group). Demographics, perioperative data, complications, and mortality were analyzed. RESULTS: Bleeding complications attributable to the surgical intervention occurred more often (19.6% vs. 10.0%, p = 0.142) and at a higher rate of re-exploratory surgery (14.3% vs. 5.0%, p = 0.088) in the heparin group without reaching statistical significance. Moreover, the heparin group patients' postoperative total length of stay was 10 days longer (17.8 ± 23.8 days vs. 8.3 ± 9.5 days, p = 0.007). There were no procedure-related deaths, no thromboembolic events, and no LVAD-related thrombosis. CONCLUSION: Our strategy of uninterrupted oral anticoagulation is safe and results in a reduction by more than half the number of days in hospital without an increase in adverse events.

Validation of mitral regurgitation reversibility in patients with HeartMate 3 LVAD implantation.

The resolution of functional mitral valve regurgitation (MR) in patients awaiting left ventricular assist device (LVAD) implantation is discussed controversially. The present study analyzed MR and echocardiographic parameters of the third-generation LVAD HeartMate 3 (HM3) over 3 years. Of 135 LVAD patients (with severe MR, n = 33; with none, mild, or moderate MR, n = 102), data of transthoracic echocardiography were included preoperatively to LVAD implantation, up to 1 month postoperatively, and at 1, 2, and 3 years after LVAD implantation. Demographic data and clinical characteristics were collected. Severe MR was reduced immediately after LVAD implantation in all patients. The echocardiographic parameters left ventricular end-diastolic diameter (P < .001), right ventricular end-diastolic diameter (P < .001), tricuspid annular plane systolic excursion (P < .001), and estimated pulmonary artery pressure (P < .001) decreased after HM3 implantation independently from the grade of MR prior to implantation and remained low during the 2 years follow-up period. Following LVAD implantation, right heart failure, ventricular arrhythmias, ischemic stroke as well as pump thrombosis and bleeding events were comparable between the groups. The incidences of death and cardiac death did not differ between the patient groups. Furthermore, the Kaplan-Meier analysis showed that survival was comparable between the groups (P = .073). HM3 implantation decreases preoperative severe MR immediately after LVAD implantation. This effect is long-lasting in most patients and reinforces the LVAD implantation without MR surgery. The complication rates and survival were comparable between patients with and without severe MR.

Comparison of periodontal parameters between patients with ischemic and dilative cardiomyopathy.

BACKGROUND: This cross-sectional study aimed in the comparison of periodontal parameters, number of remaining teeth and oral behaviour between patients with ischemic- (ICM) and non-ischemic dilative cardiomyopathy (DCM). METHODS: Patients with HF from the Department for Cardiac Surgery at the Heart Center Leipzig were included. The two groups (ICM and DCM) were composed by matching according to age, gender and smoking habits. All participants received a comprehensive periodontal examination, including a periodontal probing on six measurement points of each tooth. RESULTS: A total of 226 patients (n = 113 each group) was included. Patients in DCM group used interdental cleaning significantly more often than ICM (23.9% vs. 12.5%, p = 0.04). The majority of patients in both groups (ICM: 83.6%, DCM: 84.6%, p = 0.23) were diagnosed with stage III-IV periodontitis. Periodontal parameters were comparable between groups (p > 0.05). Variance analysis revealed no influence of the group (ICM vs. DCM) on the number of remaining teeth (p = 0.16), periodontitis stage (p = 0.27) or the periodontal inflamed surface area (p = 0.62). CONCLUSIONS: Patients with severe HF show high periodontal burden, without any differences between ICM and DCM group. Therefore, increased attention should be payed to periodontal health of patients with severe heart disease, irrespective of their underlying disease.

Benefit of Self-Managed Anticoagulation in Patients with Left Ventricular Assist Device.

BACKGROUND: The exact monitoring of the therapeutic-range international normalized ratio (INR) after left ventricular assist device (LVAD) implantation is an important aim to reduce the risk of thrombosis or bleeding complications. Service providers offer a telemedical anticoagulation service (CS). METHODS: We compared LVAD patients using the CS (n = 15) to those who received regular medical care (RMC; n = 15) to investigate if telemedicine supervision increased the INR-specific time in the therapeutic range (TTR) during anticoagulation. All patients received self-management training for phenprocoumon medication according to their INR value. INR values were documented for 12 months. A survey (scale: 1 = not satisfied and 10 = very satisfied) was used to determine patient's satisfaction and psychological well-being. RESULTS: A total of 1,798 INR measurements were analyzed. The TTRRosendaal was higher in patients undergoing RMC (78.1 ± 14.3%) compared with that in patients using the CS (58.3 ± 28.0%, p = 0.03). The patient's satisfaction with the coagulation setting at the beginning of the study (RMC: 6.7 ± 3.1, CS: 7.2 ± 3.0, p = 0.74) and psychological wellbeing (RMC: 6.5 ± 1.9, CS: 6.5 ± 2.7, p = 0.97) were comparable between both groups. CONCLUSION: We found that INR self-management is superior regarding the efficiency of post-LVAD anticoagulation therapy when compared with telemedical (CS)-based INR management in a small study cohort. Intensive training by experienced staff was able to replace CS.

Two-year outcome after implantation of a full magnetically levitated left ventricular assist device: results from the ELEVATE Registry.

AIMS: The ELEVATE Registry was designed to study long-term outcomes with the Heartmate 3 (HM3), a fully magnetically levitated centrifugal ventricular assist device, in a real-world population following CE-mark approval. METHODS AND RESULTS: A total of 540 patients, implanted in Europe and the Middle East were followed in ELEVATE. The registry included 463 patients receiving the HM3 as primary implant (Primary Implant Cohort), 19 patients underwent a pump upgrade from another device (Pump Exchange Cohort) and 58 patients who had experienced an outcome before having the possibility to sign the Informed Consent, for which only outcome data were collected (Anonymized Cohort). Data collection included demographics, survival, adverse events, EQ-5D Visual Analog Score quality of life (EQ-5D VAS QOL) questionnaire, and 6-min walk distance (6MWD). Mean age was 55.6 ± 11.7 years (89% male, 48% ischaemic cardiomyopathy). Seventy per cent of patients were in INTERMACS Profile 1-3 and 12.7% were on temporary mechanical circulatory support. Primary Implant Cohort survival was 83% after 2 years. In the Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation Primary Implant Cohort, strokes were observed in 10.2%, gastrointestinal bleedings in 9.7%, pump thrombosis in 1.5%, and outflow graft twists in 3.5%. Heartmate 3 implantation resulted in a significant and sustained improvement of functional capacity and QOL. CONCLUSION: In a real-world population, cohort implanted with the HM3 left ventricular assist device we demonstrate good long-term survival, sustained improvement of functional capacity, and low rates of adverse events (including pump thrombosis). CLINICALTRIALS.GOV IDENTIFIER: NCT02497950.

Predictors of Mortality in Primary Surgical Repair of Postinfarction Ventricular Septal Defects: The Leipzig Experience.

BACKGROUND: A postinfarction ventricular septal defect (pVSD) as a complication of acute myocardial infarction (AMI) is associated with high mortality. This retrospective, single-center study aimed to identify predictors of early and long-term outcomes in patients undergoing primary surgical repair of pVSD managed by various surgical techniques. METHODS: We reviewed data from 77 consecutive patients who underwent primary surgical repair after pVSD in our institution. Prospectively collected demographic and perioperative data were analyzed retrospectively. Predictors of 30-day mortality and long-term outcome were assessed. RESULTS: pVSD was anterior in 45 patients (58.4%) and posterior in 32 (41.6%). Buttressed mattress suture (n = 9, 11.7%), simple single septal patch (n = 34, 44.2%), simple double septal patch (n = 2, 2.6%), sandwich double patch (n = 1, 1.3%), and the infarct exclusion technique (n = 31, 40.3%) were performed for surgical closure. Fifty-three patients (68.8%) had preoperative cardiogenic shock. The 30-day mortality was 42.8% (33 patients). Independent risk factors of 30-day mortality were duration between AMI and surgery <7 days (odds ratio [OR] 5.229, P = .011), preoperative absence of diuretics (OR 6.913, P = .005), and preoperative cardiogenic shock (OR 3.558, P = .011). Cumulative survival rates at 1, 5, and 10 years were 57.1%, 57.1%, and 31.2%, respectively. CONCLUSION: In pVSD, the 30-day mortality remains high, and preoperative cardiogenic shock significantly influenced mortality in our study. None of the surgical techniques or materials used in our investigation influenced the outcome.

Oral health-related quality of life in patients with heart failure and left ventricular assist devices-results of a cross-sectional study.

OBJECTIVES: The aim of this cross-sectional study was to compare oral health-related quality of life (OHRQoL) of patients with left ventricular assist device (LVAD) and heart failure (HF). MATERIAL AND METHODS: Seventy-four patients with LVAD were recruited from University Department for Cardiac Surgery, Leipzig Heart Center, Germany. A group of 72 patients with HF was composed by matching (age, gender, smoking). The German short form of oral health impact profile (OHIP G14) was applied. Health-related quality of life (HRQoL) was measured by short form 36 survey (SF-36). Dental conditions (decayed-, missing- and filled-teeth [DMF-T]), remaining teeth and periodontal findings were assessed. STATISTICS: t-test, Mann-Whitney U test, Kruskal-Wallis test, chi-square or Fisher test, linear regression. RESULTS: Age, gender, smoking, underlying disease, co-morbidities and oral findings were comparable between groups (p > 0.05). OHIP G14 sum score was 3.53 ± 6.82 (LVAD) and 2.92 ± 5.35 (HF; p = 0.70), respectively. The scales SF-36 physical functioning (p = 0.05) and SF-36 social functioning (p < 0.01) were worse in LVAD. In the LVAD group, the DMF-T and remaining teeth negatively correlated with OHIP G14 sum score (p < 0.01). In HF patients, positive correlations were found between OHIP G14 and D-T (p < 0.01) and remaining teeth (p = 0.04). Moreover, DMF-T (p = 0.03) and remaining molars/premolars (p = 0.02) were negatively correlated with SF-36 scales in HF. CONCLUSIONS: Oral health and OHRQoL was comparable between LVAD and HF; thereby, OHRQoL reflected the clinical oral status. CLINICAL RELEVANCE: Dental care, with beginning in early stage of HF, should be fostered to preserve teeth and support quality of life before and after LVAD implantation.

Predictors of Physical Capacity 6 Months After Implantation of a Full Magnetically Levitated Left Ventricular Assist Device: An Analysis From the ELEVATE Registry.

BACKGROUND: In patients with a continuous-flow left ventricular assist device, preimplant predictors of poor physical performance are not well-described. We aimed to identify predictors of inability to walk more than 300 m on 6-minute walk test (6MWT) 6 months after HeartMate 3 implantation. METHODS AND RESULTS: Using data from the European Registry of Patients Implanted With a Full Magnetically Levitated LVAD, patients with available 6MWT at 6 months after implantation were included (N = 194) and grouped according to 6MWT distance (6MWD) of >300 m (n = 150) or 6MWD of <300 m (n = 44). Patients walking <300 m were older (60 ± 10 vs 52 ± 12 years; P < .001), more often New York Heart Association functional class IV (63% vs 42%; P = .03), and more often had type 2 diabetes (43% vs 17%; P < .001) at implantation. Atrial fibrillation was seen in 57% in those with a 6MWT of <300 m vs 31% in those walking longer (P < .002). Further, hemoglobin and estimated glomerular filtration rate was lower in those walking <300 m (both P < .01). In multivariable regression analysis, independent predictors of a 6MWD of <300 m were: atrial fibrillation (odds ratio [OR], 3.22; 95% confidence interval [CI], 1.12-8.67), older age (OR for 10-year increment, 2.81; 95% CI, 1.55-5.07), New York Heart Association functional class IV (OR, 3.37; 95% CI, 1.27-8.98), and Interagency Registry for Mechanically Assisted Circulatory Support profile 1 or 2 (OR, 6.53; 95% CI, 1.92-22.19). CONCLUSIONS: Six months after HeartMate 3 implantation, 77% of patients walked >300 meters in 6 minutes. Apart from age and measures of heart failure severity, atrial fibrillation at implantation is an independent predictor of low 6MWD at 6 months after implantation.

Quantitative coronary computed tomography angiography for the detection of cardiac allograft vasculopathy.

OBJECTIVES: To associate coronary wall volume and composition, derived from coronary computed tomography angiography (CTA), with cardiac allograft vasculopathy (CAV) detected on invasive coronary angiography (ICA) in heart-transplanted (HTX) patients. METHODS: We included consecutive adults who received ICA and coronary CTA for evaluation of CAV ≥ 10 months after HTX. In all coronary segments, we assessed lumen and wall volumes and segmental length, calculated volume-length ratio (VLR) (volumes indexed by segmental length; mm3/mm), wall burden (WB) (wall/wall + lumen volumes; %), and assessed proportions of calcified, fibrotic, fibro-fatty, and low-attenuation tissue (%) in coronary wall. We rendered independent CTA measures associated with CAV by ICA, tested their discriminatory capacity, and assessed concordance between CTA and ICA. RESULTS: Among 50 patients (84% men; 53.6 ± 11.9 years), we analyzed 632 coronary segments. Mean interval between HTX and CTA was 6.7 ± 4.7 years and between ICA and CTA 1 (0-1) day. Segmental VLR, WB, and proportion of fibrotic tissue were independently associated with CAV (OR = 1.06-1.27; p ≤ 0.002), reaching a high discriminatory capacity (combination of all three: AUC = 0.84; 95%CI, 0.75-0.90). Concordance between CTA and ICA was higher in advanced CAV (88%) compared with that in none (37%) and mild (19%) CAV. Discordance was primarily driven by a large number of segments with coronary wall changes on CTA but without luminal stenoses on ICA (177/591; 25%). CONCLUSION: CTA-derived coronary wall VLR, WB, and the proportion of fibrotic tissue are independent markers of CAV. Combination of these three parameters may aid the detection of early CAV not detected by ICA, the current standard of care. KEY POINTS: • Coronary CTA detects CAV in HTX patients. • Coronary wall volume-length ratio, wall burden, and proportion of fibrotic tissue are independently associated with CAV. • In contrast to ICA, coronary CTA may identify the early stages of CAV.

Oral health-related quality of life of patients after heart transplantation and those with heart failure is associated with general health-related quality of life: a cross-sectional study.

PURPOSE: The aim of this cross-sectional study was to examine the oral health-related quality of life (OHRQoL) in patients after heart transplantation (HTx) and those with heart failure (HF). METHODS: In total, 186 participants (HTx: 104, HF: 82) were recruited from the University Department for Cardiac Surgery, Leipzig Heart Centre, Germany. OHRQoL was assessed with the German short form of the oral health impact profile (OHIP-G14). Health-related quality of life (HRQoL) was evaluated using the short form 36 survey (SF-36). Furthermore, the dental and periodontal treatment need was recorded. RESULTS: With an OHIP-G14 sum score of 6.58 ± 6.40 [5; 2.5-8] in the HTx group and 5.54 ± 5.47 [5; 2-7] in the HF group, no clinically relevant or statistically significant difference was apparent (p = 0.39). The SF-36 scales for physical functioning, role-physical, general health and vitality were significantly worse in the HF group compared with the HTx group (pi < 0.01). A worse SF-36 physical component summary was significantly associated with a higher OHIP-G14 sum score (HTx: p < 0.01, HF: p = 0.04). In the HTx group, a significant association was also observed for the mental component summary (p < 0.01). Multiple regression analysis revealed physical component summary (p = 0.04) and mental component summary (p < 0.01) in HTx, and physical component summary (p = 0.02), mental component summary (p = 0.02) and smoking (p < 0.01) as significant predictors for OHIP G14 in HF. CONCLUSION: The OHRQoL in HF and HTx patients appears to be mainly associated with general HRQoL. Therefore, multidisciplinary dental care concepts may be recommended to improve oral health conditions in these patients.

Midterm results after St Jude Medical Epic porcine xenograft for aortic, mitral, and double valve replacement.

BACKGROUND: The aim of this study was to evaluate the results after stented porcine xenograft implantation (Epic, SJM, St Paul, MN) with Linx anticalcification treatment in elderly patients at our high-volume tertiary care center. METHODS: A total of 3825 patients undergoing aortic (AVR = 2441), mitral (MVR = 892), or double valve (DVR = 492) replacement between 11/2001 and 12/2017 with Epic xenografts were evaluated. Outcomes were assessed by reviewing the prospectively acquired hospital database results, and regular annual follow-up information was acquired from questionnaires or telephone interviews. RESULTS: For patients undergoing AVR, MVR, DVR, age at surgery were 76.4 ± 6, 71.2 ± 9, 72.9 ± 8 years; active endocarditis was an indication for valve surgery in 4.5%, 20.7%, 19.7%; and the predicted median (interquartile range [IQR]) mortality risk (EuroSCORE II) was 5.2% (3.1%-9.4%), 7.5% (3.9%-16.2%), 9.9% (6.0%-19.6%), respectively. Median follow-up was 3.04 (IQR: 0.18-5.21). Thirty-day survival was 91.2% ± 0.6%, 87.6% ± 0.1.1%, 84.7% ± 1.6%; and 10-year survival was 56.7% ± 1.0%, 59.4% ± 2.5%, 50.45% ± 3.1%, respectively. Patients who underwent MVR versus AVR were at significant increased risk for reoperation for endocarditis (adjusted odds ratio; 2.2, 95% confidence interval; 1.29-3.7; P = .003). There was no significant difference in all-cause mortality at midterm in AVR vs MVR in the matched cohort (P = .85). CONCLUSIONS: Implantation of the Epic stented porcine xenograft is associated with acceptable survival and freedom from valve-related complications or reoperation due to structural valve disease at midterm follow-up.

Does oral health-related quality of life of patients after solid organ transplantation indicate a response shift? Results of a systematic review.

BACKGROUND: The physical oral health and dental behaviour of patients after solid organ transplantation (SOT) has repeatedly been reported as insufficient. The objective of this systematic review was to detect whether the oral health-related quality of life (OHRQoL) of patients after SOT is reduced compared to that of healthy individuals. METHODS: A systematic literature search was performed by two independent individuals based on the PubMed, Web of Science and Scopus databases by using the following search terms: "transplantation" AND "oral health-related quality of life". The findings were checked to determine eligibility, whereby publication prior to 31 October 2020, examination of adult patients (age at least 18 years) with SOT, reporting of an OHRQoL outcome and full text in English language were the prerequisites for inclusion in the qualitative analysis. Quality appraisal of the included studies was performed using the Agency for Healthcare Research and Quality methodology checklist. RESULTS: Seven of 25 studies that examined patients after kidney (3), heart (2), liver (1) and lung transplantation (1) were included. Four studies included healthy controls, and five studies included a cohort of patients before transplantation for comparison. Clinical oral health examinations were heterogeneous between groups. The majority of studies (5/7) applied the short form of the "Oral Health Impact Profile" (OHIP 14) to assess OHRQoL. The OHIP 14 values ranged between 1.7 and 8.9 across studies, indicating an unaffected or just slightly reduced OHRQoL. Only one study found better OHRQoL in patients after SOT compared to a group before SOT, and one study confirmed worse OHRQoL of SOT recipients compared to a healthy control. Only two studies revealed an association between OHRQoL and oral health parameters. Furthermore, two studies each found a relationship between OHRQoL and general health-related quality of life or disease-related parameters. CONCLUSIONS: Patients after SOT show an unaffected or only slightly reduced OHRQoL, which was mainly independent of the insufficient oral status. This might indicate a shift in the perception threshold for oral diseases and conditions caused by the general health burden related to the SOT.

Comparing everolimus-based immunosuppression with reduction or withdrawal of calcineurin inhibitor reduction from six months after heart transplantation: the randomized MANDELA study.

In the 12-month, open-label MANDELA study, patients were randomized at month 6 after heart transplantation to (i) convert to calcineurin inhibitor (CNI)-free immunosuppression with everolimus (EVR), mycophenolic acid and steroids (CNI-free, n=71), or to (ii) continue reduced-exposure CNI, with EVR and steroids (EVR/redCNI, n=74). Tacrolimus was administered in 48.8% of EVR/redCNI patients and 52.6% of CNI-free patients at radomization. Both strategies improved and stabilized renal function based on the primary endpoint (estimated GFR at month 18 post-transplant post-randomization) with superiority of the CNI-free group versus EVR/redCNI : mean 64.1mL/min/1.73m2 versus 52.9mL/min/1.73m2 ; difference +11.3mL/min/1.73m2 (p<0.001). By month 18, estimated GFR had increased by ≥10mL/min/1.732 in 31.8% and 55.2% of EVR/redCNI and CNI-free patients, respectively, and by ≥25 mL/min/1.73m2 in 4.5% and 20.9%. Rates of biopsy-proven acute rejection (BPAR) were 6.8% and 21.1%; all cases were without hemodynamic compromise. BPAR was less frequent with EVR/redCNI versus the CNI-free regimen (p=0.015); 6/15 episodes in CNI-free patients occurred with EVR concentration <5ng/mL. Rates of adverse events and associated discontinuations were comparable EVR/redCNI from month 6 achieved stable renal function with infrequent BPAR. One-year renal function can be improved by early conversion to EVR-based CNI-free therapy but requires close EVR monitoring. This article is protected by copyright. All rights reserved.

Ischemic Cardiomyopathy Affects the Thioredoxin System in the Human Myocardium.

BACKGROUND: Oxidative stress due to reactive oxygen species (ROS) production is a key factor in the development of heart failure (HF). This study investigated the thioredoxin (Trx) system, which plays a major role in antioxidant defense, in patients suffering from ischemic (ICM) or dilated (DCM) cardiomyopathy. METHODS AND RESULTS: Myocardial tissue from ICM (n = 13) and DCM (n = 13) patients, as well as septal tissue of patients with aortic stenosis but without diagnosed hypertrophic cardiomyopathy or subaortic stenosis (control; n = 12), was analyzed for Trx1, Trx-interacting protein (TXNIP) and E3 ligase ITCH (E3 ubiquitin-protein ligase Itchy homolog) expression. Trx-reductase 1 (TXNRD1) amount and activity, cytosolic cytochrome C content, and apoptosis markers were quantified by means of enzyme-linked immunosorbent assay and multiplexing. Compared with control samples, ITCH and Trx1 expression, TXNRD1 amount and activity were reduced and TXNIP expression was increased in ICM (ITCH: P = .013; Trx1: P = .028; TXNRD1 amount: P = .035; TXNRD1 activity: P = .005; TXNIP: P = .014) but not in DCM samples. A higher level of the downstream apoptosis marker caspase-9 (ICM: 582 ± 262 MFI [P = .995]; DCM: 1251 ± 548 MFI [P = .002], control: 561 ± 214 MFI) was detected in DCM tissue. A higher expression of Bcl-2 was found in DCM (P = .011). CONCLUSION: The Trx system was impaired in ICM but not in DCM. ITCH appeared to be responsible for the down-regulation of the Trx system. ROS-induced mitochondrial instability appeared to play a role in DCM.

Six-month outcomes after treatment of advanced heart failure with a full magnetically levitated continuous flow left ventricular assist device: report from the ELEVATE registry.

Aims: The ELEVATE registry was planned to study post-approval outcomes with HeartMate 3™ (HM3), a fully magnetically levitated continuous flow left ventricular assist device (LVAD). Methods and results: A total of 482 patients provided consent to participate in ELEVATE (enrolled cohort). Data collection included baseline demographics, survival, adverse events, quality of life (QOL) [EuroQoL-5 Dimensions visual analogue scale (VAS), and 6-minute walk distance (6MWD)]. An additional 58 patients were implanted with HM3 during the same period but expired or were explanted prior to consent, and only survival data were collected (anonymized cohort). We report the 6-month outcomes of the patients who received HM3 as their primary implant (n = 463) and the survival of the 540 patients in the full cohort (enrolled + anonymized). Baseline characteristics included a mean age of 55.6 ± 11.7 years, 89% male, 48% ischaemic aetiology, and 70% on inotropes. The majority of patients (66%) were bridge-to-transplantation (BTT) and 32% were INTERMACS profile 1-2. Full cohort survival at 6 months was 82 ± 2%. In the enrolled primary implant patients, there was no incidence of pump thrombosis, major bleeding was 25%, major infection 35%, and any stroke type 5%. Functional capacity improved significantly (Δ6MWD 230 ± 191 m) as did QOL (ΔVAS 31 ± 23). Freedom from unplanned rehospitalizations at 6 months was 68 ± 2%. Conclusion: The 6-month outcomes of the HM3 LVAD demonstrate a highly reliable, thrombosis free, device with low incidence of stroke and improved functional capacity, and QOL. ClinicalTrials. gov Identifier: NCT02497950.

Differences of early immunological responses in on-pump versus off-pump cardiac surgery.

INTRODUCTION: Cardiopulmonary bypass surgery is accompanied by an inflammatory response and pulmonary dysfunction that renders patients vulnerable to postoperative complications. The majority of studies investigating the inflammatory response in cardiopulmonary bypass focus on cytokine measurements. This study investigated the early response of peripheral blood cell types and early changes in lung tissue in on-pump versus off-pump cardiopulmonary bypass surgery. METHODS: Landrace pigs were assigned to the following groups (n = 6 per group): 1. off-pump cardiopulmonary bypass, 2. conventional cardiopulmonary bypass, 3. heparin-coated cardiopulmonary bypass, 4. surface-reduced cardiopulmonary bypass, and 5. surface-reduced cardiopulmonary bypass plus lung perfusion. Surgery was performed under mild hyperthermia (32°C), with 90-minute ischemia and 180-minute reperfusion. Histological and flow cytometric analyses were performed. RESULTS: Lung water content increased during reperfusion in heparin-coated (84.63 ± 2.99%) compared to conventional cardiopulmonary bypass (76.33 ± 4.56%, p = 0.04). Alveolar septal thickness increased during ischemia at heparin-coated (p < 0.01) and surface-reduced cardiopulmonary bypass plus lung perfusion (p = 0.05). Tumor necrosis factor expression increased significantly (p < 0.01) in peribronchial, perivascular, and peripheral lung areas in all on-pump groups, but not in off-pump cardiopulmonary bypass. The usage of heparin-coated cardiopulmonary bypass led to increased percentages of CD3+CD4+ (p = 0.03) and CD3+CD8+ (p = 0.01) T cells compared to an uncoated device. Natural killer and mature B lymphocytes decreased at conventional and surface-reduced cardiopulmonary bypass plus lung perfusion. Activated granulocytes and macrophages increased at conventional cardiopulmonary bypass and heparin-coated cardiopulmonary bypass. CONCLUSION: Off-pump cardiopulmonary bypass induces less immunological response and lung injury than on-pump surgery. The reduction of cardiopulmonary bypass surface reduces the inflammatory immune response induced by cardiopulmonary bypass. Lung perfusion of surface-reduced cardiopulmonary bypass diminished the extravasation caused by surface reduction of the cardiopulmonary bypass.

The Ubiquitin Proteasome System in Ischemic and Dilated Cardiomyopathy.

Dilated (DCM) and ischemic cardiomyopathies (ICM) are associated with cardiac remodeling, where the ubiquitin-proteasome system (UPS) holds a central role. Little is known about the UPS and its alterations in patients suffering from DCM or ICM. The aim of this study is to characterize the UPS activity in human heart tissue from cardiomyopathy patients. Myocardial tissue from ICM (n = 23), DCM (n = 28), and control (n = 14) patients were used to quantify ubiquitinylated proteins, E3-ubiquitin-ligases muscle-atrophy-F-box (MAFbx)/atrogin-1, muscle-RING-finger-1 (MuRF1), and eukaryotic-translation-initiation-factor-4E (eIF4E), by Western blot. Furthermore, the proteasomal chymotrypsin-like and trypsin-like peptidase activities were determined fluorometrically. Enzyme activity of NAD(P)H oxidase was assessed as an index of reactive oxygen species production. The chymotrypsin- (p = 0.71) and caspase-like proteasomal activity (p = 0.93) was similar between the groups. Trypsin-like proteasomal activity was lower in ICM (0.78 ± 0.11 µU/mg) compared to DCM (1.06 ± 0.08 µU/mg) and control (1.00 ± 0.06 µU/mg; p = 0.06) samples. Decreased ubiquitin expression in both cardiomyopathy groups (ICM vs. control: p < 0.001; DCM vs. control: p < 0.001), as well as less ubiquitin-positive deposits in ICM-damaged tissue (ICM: 4.19% ± 0.60%, control: 6.28% ± 0.40%, p = 0.022), were detected. E3-ligase MuRF1 protein expression (p = 0.62), NADPH-oxidase activity (p = 0.63), and AIF-positive cells (p = 0.50). Statistical trends were detected for reduced MAFbx protein expression in the DCM-group (p = 0.07). Different levels of UPS components, E3 ligases, and UPS activation markers were observed in myocardial tissue from patients affected by DCM and ICM, suggesting differential involvement of the UPS in the underlying pathologies.