Not to Rush-Laboratory Parameters and Procedural Complications in Patients Undergoing Left Atrial Appendage Closure.

Background: As a preventive procedure, minimizing periprocedural risk is crucially important during left atrial appendage closure (LAAC). Methods: We included consecutive patients receiving LAAC at nine centres and assessed the relationship between baseline characteristics and the acute procedural outcome. Major procedural complications were defined as all complications requiring immediate invasive intervention or causing irreversible damage. Logistic regression was performed and included age and left-ventricular function. Furthermore, the association between acute complications and long-term outcomes was evaluated. Results: A total of 405 consecutive patients with a median age of 75 years (37% female) were included. 47% had a history of stroke. Median CHA2DS2-VASc score was 4 (interquartile range, 3−5) and the median HAS-BLED score was 3 (2−4). Major procedural complications occurred in 7% of cases. Low haemoglobin (OR 0.8, 95% CI 0.65−0.99 per g/dL, p = 0.040) and end-stage kidney disease (OR 13.0, CI 2.5−68.5, p = 0.002) remained significant in multivariate analysis. Anaemia (haemoglobin < 12 and < 13 g/dL in female and male patients) increased the risk of complications 2.2-fold. Conclusions: The major complication rate was low in this high-risk patient population undergoing LAAC. End-stage kidney disease and low baseline haemoglobin were independently associated with a higher major complication rate.

Indications and Outcome in Patients Undergoing Left Atrial Appendage Closure-The Austrian LAAC Registry.

BACKGROUND: Complete real-world data on the indications and outcomes of left atrial appendage closure (LAAC) outside of clinical trials are rare. In this study, we stratified patients undergoing LAAC by indication groups. METHODS: This analysis of the national multicentre Austrian LAAC Registry comprised all patients that underwent LAAC up until 2018 at the currently active centres in Austria. The baseline characteristics, procedural details and outcomes between the following indication groups were compared: bleeding as an indication for LAAC ("bleeding" group) vs. thromboembolism despite oral anticoagulation (OAC; "thromboembolism" group) vs. an intolerance to OAC for reasons other than the above ("other" group). RESULTS: The analysis included 186 patients, with 59.7% in the "bleeding" group, 8.1% in the "thromboembolism" group and 32.2% in the "other" group. The CHADS2 score was the highest in the "thromboembolism" group and the HAS-BLED score was the highest in the "bleeding" group. The procedural outcomes were similar between groups (implantation success, 97.3%), with major complications occurring in 7.0% of patients. One-year survival free from stroke, bleeding or LAAC-associated hospitalisation was 83.9%, 90.0% and 81.4% in the "bleeding", "thromboembolism" and "other" groups, respectively (p = 0.891). CONCLUSIONS: In routine clinical practice, LAAC was used in a heterogeneous patient population with atrial fibrillation (AF) and contraindication, inefficacy or intolerance to OAC. The long-term outcome was favourable in all groups.

In-stent restenosis in bare metal stents versus sirolimus-eluting stents after primary coronary intervention for acute myocardial infarction and subsequent transcoronary transplantation of autologous stem cells.

BACKGROUND: Following stenting for acute myocardial infarction, transcoronary transplantation of granulocyte-colony stimulating factor (G-CSF) mobilized autologous stem cells (ASC) has been shown to result in an increased in-stent restenosis rate of bare metal stents (BMS). HYPOTHESIS: This study sought to compare the extent of neointimal growth in BMS and sirolimus-eluting stents (SES) after primary implantation, and subsequent transcoronary transplantation of G-CSF mobilized stem cells. METHODS: Patients with stenting of the left anterior descending coronary artery for acute anterior myocardial infarction were randomly assigned to receive a BMS or SES. Intracoronary stem cell injection was performed after G-CSF application for at least 4 d and cell apheresis. The angiograms obtained after cell transplantation and after 6 mo were analyzed by quantitative coronary angiography. RESULTS: We performed primary stenting and stem cell transplantion in 16 patients who received a BMS (n = 8) or an SES (n = 8). In 2 patients with a BMS, late stent thrombosis occurred after 58 d and 177 d, respectively. In the remaining patients, control angiography after 6 mo revealed in-stent restenosis of >50% in no patients with SES but in 4 patients with BMS (67%). Late lumen loss and in-stent plaque volume were significantly higher in patients with BMS compared with patients with SES. CONCLUSIONS: Compared with BMS, SES impair in-stent intima hyperplasia after stenting for acute myocardial infarction and transcoronary transplantation of G-CSF mobilized ASC.

Cardiotoxicity with rituximab, cyclophosphamide, non-pegylated liposomal doxorubicin, vincristine and prednisolone compared to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone in frontline treatment of patients with diffuse large B-cell lymphoma: A randomised phase-III study from the Austrian Cancer Drug Therapy Working Group [Arbeitsgemeinschaft Medikamentöse Tumortherapie AGMT](NHL-14).

BACKGROUND: Chemoimmunotherapy containing rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) is the standard treatment for diffuse large B-cell lymphoma (DLBCL). Doxorubicin may induce early and late cardiotoxicity. Non-pegylated liposomal (NPL) doxorubicin may reduce cardiotoxicity. PATIENTS AND METHODS: Patients with untreated CD20+ DLBCL were randomised to conventional R-CHOP chemoimmunotherapy or rituximab, cyclophosphamide, non-pegylated liposomal doxorubicin, vincristine and prednisolone (R-COMP) with doxorubicin substituted by NPL-doxorubicin. Left ventricular ejection fraction (LVEF) and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels were measured before each treatment cycle and after the end of treatment. RESULTS: The mean LVEF of 178 and 158 measurements in the R-COMP and R-CHOP arms was 63.31% and 62.25%, respectively (P = 0.167). During treatment the LVEF measurements were below 50% in 10/218 (4.6%) in the R-COMP arm and 31/196 (15.8%) in the R-CHOP arm (P<0.001). Thirty-six of 40 (90%) patients in the R-COMP arm, but only 24/36 (66.7%) in the R-CHOP arm had all NT-proBNP levels below 400 pg/ml during and at the end of treatment (P = 0.013). There were more serious adverse events in the R-CHOP arm (26 versus 40, P = 0.029). Infections were more common (15 versus 28) in the R-CHOP arm. INTERPRETATION: In patients with normal cardiac function, six cycles of R-CHOP resulted in a low rate of early cardiotoxicity. NPL-doxorubicin did not reduce cardiotoxicity, although cardiac safety signals were elevated in R-CHOP compared to R-COMP. FUNDING: Cephalon provided the Arbeitsgemeinschaft Medikamentöse Tumortherapie with NPL-doxorubicin and an unrestricted grant, but was not involved in the study protocol, data acquisition, data analysis or the writing of the paper.

Individual-patient visit-by-visit office and ambulatory blood pressure measurements over 24months in patients undergoing renal denervation for hypertension.

BACKGROUND: Renal denervation (RDN) is a promising treatment option in addition to medical antihypertensive treatment in patients suffering from resistant hypertension. Despite the growing interest in RDN, only few long-term results are published so far. METHODS: We systematically investigated the effects of RDN on ABPM in a consecutive series of patients with resistant hypertension out to 24 months. Office BP measurements and ABPM assessment were offered at 3, 6, 12 and 24 months. The patients with an average systolic BP reduction of more than 10 mmHg in office BP 6months after RDN were classified as responders. Additional to this classical responder concept, we categorized response to RDN by an individual-patient visit-by-visit evaluation of office BP and 24-hour-BP, separately. RESULTS: We included 32 patients. In 21 patients (65.6%) we found a mean systolic BP reduction >10 mmHg in office BP six months after RDN. These patients were classified as responders. In responders, mean office BP dropped from 175.3 ± 15.9/96 ± 14.2 mmHg to 164.8 ± 24.4/93.2 ± 10.4 mmHg (p=0.040/p=0.323) and mean 24-h BP in ABPM decreased from 146.8 ± 17.0/89.1 ± 11 mmHg to 136.8 ± 15.0/83.2 ± 10.7 mmHg after 24 months (p=0.034/p=0.014). Additionally, we performed a visit-by-visit evaluation of all patients and results were divided in larger-than-median and smaller-than-median response. By this evaluation, we found a high variation of office BP reductions and the 24-hour BP results demonstrated a significant BP reduction in patients with larger-than-median response, which sustained over the 24 months of follow-up. CONCLUSIONS: In contrast to the observed variation of office BP measurements, ABPM demonstrated a reproducible and sustained significant BP reduction in patients with larger-than-median response to RDN.

Efficacy and safety of the pulsed infusions of levosimendan in outpatients with advanced heart failure (LevoRep) study: a multicentre randomized trial.

AIMS: The aim of this study was to determine whether intermittent ambulatory treatment with levosimendan would improve functional capacity, quality of life, and event-free survival in patients with advanced heart failure. METHODS AND RESULTS: This was a prospective, randomized, double-blind, placebo-controlled, multicentre, parallel-group trial of pulsed infusions of levosimendan in 120 outpatients with advanced heart failure (EF ≤35%, NYHA class III or IV). The study was conducted at 11 centres in Austria, Greece, and Germany. Levosimendan (0.2 µg/kg/min) or placebo was administered for 6 h at 2-week intervals over 6 weeks, in addition to standard care therapy. The primary outcome was the proportion of patients with a ≥20% improvement in the 6 min walk test and a ≥15% score increase on the Kansas City Cardiomyopathy Questionnaire at the end of the 24-week study period. Secondary outcomes included event-free survival after 24 weeks. Analyses were performed on an intention-to-treat basis. The primary endpoint was reached in 19% of patients receiving levosimendan and 15.8% of patients receiving placebo (odds ratio 1.25; 95% confidence interval 0.44-3.59; P = 0.810). Cardiac death (four vs. one), heart transplants (two vs. one), and acute heart failure (14 vs. nine) were more frequent with placebo as compared with levosimendan. The incidence of side effects was comparable between groups. CONCLUSION: Intermittent ambulatory treatment with levosimendan in patients with advanced heart failure did not improve significantly functional capacity or quality of life as compared with placebo. An adequately powered, event-driven trial is warranted to enlarge on our findings. TRIAL REGISTRATION: NCT01065194.

TIMI 3 flow after primary angioplasty is an important predictor for outcome in patients with acute myocardial infarction.

BACKGROUND: Growing evidence suggests that poor coronary blood flow after primary percutaneous coronary intervention (PCI) is associated with unfavorable clinical out-come. We retrospectively evaluated data from our single center "real world patients" database of patients undergoing primary PCI to determine differences in clinical and angiographic patterns in patients with or without restoring thrombolysis in myocardial infarction (TIMI) flow 3. METHODS AND RESULTS: Between 2001 and 2006, 500 patients underwent primary PCI for STEMI. In 430 patients, post-interventional TIMI flow 3 could be established. In this group, in-hospital mortality was significant lower (6.4% Vs. 32.9%; P < 0.0001), left ventricular ejection fraction was better (51.3 Vs. 44.2%; P < 0.0001), and prehospital fibrinolytic therapy (6.3% Vs. 14.3%; P = 0.015), cardiogenic shock (10.9% Vs. 24.3%; P = 0.002) and use of intra-aortic balloon pump were all more unlikely (5.8% Vs. 11.4%; P = 0.045) compared to patients with TIMI flow < or = 2. In patients with post-interventional TIMI flow < or = 2 the left anterior descending coronary artery (LAD) was significantly more often seen as the target vessel (54.3% Vs. 44.6%; P = 0.039). A regressions analysis showed that predictors leading to such flow patterns are diabetes (P = 0.013), pre-hospital fibrinolytic therapy (P = 0.017), cardiogenic shock (P = 0.002) and a 3-vessel disease (P = 0.003). After 6 months, patients without restored normal TIMI flow had worse New York Heart Association functional class (NYHA), and had to undergo repeat coronary angiography more often. CONCLUSION: Post-interventional TIMI flow < or = 2 is strongly associated with adverse out-come during hospitalization and after 6 months following hospitalization.