Towards a Precise NMR Quantification of Acute Phase Inflammation Proteins from Human Serum.

Nuclear Magnetic Resonance (NMR) spectra of human serum and plasma show, besides metabolites and lipoproteins, two characteristic signals termed GlycA and B arising from the acetyl groups of glycoprotein glycans from acute phase proteins, which constitute good markers for inflammatory processes. Here, we report a comprehensive assignment of glycoprotein glycan NMR signals observed in human serum, showing that GlycA and GlycB signals originate from Neu5Ac and GlcNAc moieties from N-glycans, respectively. Diffusion-edited NMR experiments demonstrate that signal components can be associated with specific acute phase proteins. Conventionally determined concentrations of acute phase glycoproteins correlate well with distinct features in NMR spectra (R2 up to 0.9422, p-value <0.001), allowing the simultaneous quantification of several acute phase inflammation proteins. Overall, a proteo-metabolomics NMR signature of significant diagnostic potential is obtained within 10-20 min acquisition time. This is exemplified in serum samples from COVID-19 and cardiogenic shock patients showing significant changes in several acute phase proteins compared to healthy controls.

Platelets regulate ischemia-induced revascularization and angiogenesis by secretion of growth factor-modulating factors.

In ischemic tissue, platelets can modulate angiogenesis. The specific factors influencing this function, however, are poorly understood. Here, we characterized the complement anaphylatoxin C5a-mediated activation of C5a receptor 1 (C5aR1) expressed on platelets as a potent regulator of ischemia-driven revascularization. We assessed the relevance of the anaphylatoxin receptor C5aR1 on platelets in patients with coronary artery disease as well as those with peripheral artery disease and used genetic mouse models to characterize its significance for ischemia and growth factor-driven revascularization. The presence of C5aR1-expressing platelets was increased in the hindlimb ischemia model. Ischemia-driven angiogenesis was significantly improved in C5aR1-/- mice but not in C5-/- mice, suggesting a specific role of C5aR1. Experiments using the supernatant of C5a-stimulated platelets suggested a paracrine mechanism of angiogenesis inhibition by platelets by means of antiangiogenic CXC chemokine ligand 4 (CXCL4, PF4). Lineage-specific C5aR1 deletion verified that the secretion of CXCL4 depends on C5aR1 ligation on platelets. Using C5aR1-/-CXCL4-/- mice, we observed no additional effect in the revascularization response, underscoring a strong dependence of CXCL4 secretion on the C5a-C5aR1-axis. We identified a novel mechanism for inhibition of neovascularization via platelet C5aR1, which was mediated by the release of antiangiogenic CXCL4.

Impact of moderate or severe left ventricular outflow tract calcification on clinical outcomes of patients with severe aortic stenosis undergoing transcatheter aortic valve implantation with self- and balloon-expandable valves: a post hoc analysis from the SOLVE-TAVI trial.

BACKGROUND: Left ventricular outflow tract (LVOT) calcification has been associated with worse outcomes in patients undergoing transcatheter aortic valve implantation (TAVI) and may influence the selection of prosthetic valve type. AIMS: We aimed to evaluate the impact of LVOT calcification on outcomes after TAVI with a self-expanding valve (SEV) versus a balloon-expandable valve (BEV). METHODS: Patients of the SOLVE-TAVI trial, randomised to Edwards SAPIEN 3 or Medtronic Evolut R, were divided according to LVOT calcification into no/mild (≤1 calcium nodule extending <5 mm and covering <10% of the LVOT perimeter) and moderate/severe LVOT calcification groups. The primary endpoint was a composite of death, stroke, moderate/severe paravalvular regurgitation, permanent pacemaker implantation and annulus rupture at 30 days. Additional endpoints included all-cause and cardiovascular mortality at 1 year. RESULTS: Out of 416 eligible patients, moderate/severe LVOT calcification was present in 143 (34.4%). Moderate/severe LVOT calcification was associated with significantly longer fluoroscopy time and higher rates of pre- and post-dilation. Regardless of the LVOT calcification group, there was no significant difference in the primary endpoint associated with the valve type (no/mild LVOT calcification group: SEV 25.0% vs BEV 27.0%; hazard ratio [HR] 1.10, 95% confidence interval [95% CI]: 0.68-1.73; p=0.73 and moderate/severe LVOT calcification group: SEV 25.0% vs BEV 19.4%; HR 0.76, 95% CI: 0.38-1.61; p=0.49), no significant interaction between LVOT calcification and valve type (pint=0.29) and no differences between SEV vs BEV within LVOT calcification groups regarding 1-year all-cause and cardiovascular mortality. CONCLUSIONS: Moderate/severe LVOT calcification was associated with longer fluoroscopy time and an increased need for pre- and post-dilation, but not with a higher incidence of early and mid-term adverse clinical outcomes, regardless of valve type. (ClinicalTrials.gov: NCT02737150).

PrEdictive value of coMbined pre-test proBability and blOod gas anaLysis In pulmonary emboliSM-the EMBOLISM study.

In patients with suspected pulmonary embolism (PE), the number of unnecessary computed tomography pulmonary angiography (CTPA) scans remains high, especially in patients with low pre-test probability (PTP). So far, no study showed any additional benefit of capillary blood gas analysis (BGA) in diagnostic algorithms for PE. In this retrospective analysis of patients with suspected PE and subsequent CTPA, clinical data, D-dimer levels and BGA parameters (including standardized PaO2) were analyzed. Logistic regression analyses were performed to identify independent predictors for PE and reduce unnecessary CTPA examinations in patients with low PTP according to Wells score. Of 1538 patients, PE was diagnosed in 433 patients (28.2%). The original Wells score (odds ratio: 1.381 [95% CI 1.300-1.467], p < 0.001) and standardized PaO2 (odds ratio: 0.987 [95% CI 0.978-0.996], p = 0.005) were independent predictors for PE. After cohort adjustment for low PTP a D-dimer cut-off < 1.5 mg/L (278 patients (18.1%) with 18 PE (6.5%)) was identified in which a standardized PaO2 > 65 mmHg reduced the number of unnecessary CTPA by 31.9% with a 100% sensitivity. This approach was further validated in additional 53 patients with low PTP. In this validation group CTPA examinations were reduced by 32.7%. No patient with PE was missed. With our novel algorithm combining BGA testing with low PTP according to Wells score, we were able to increase the D-Dimer threshold to 1.5 mg/L and reduce CTPA examinations by approximately 32%.

Stand-alone Focal Impulse and Rotor Modulation (FIRM) ablation versus second-generation cryoballoon pulmonary vein isolation for paroxysmal atrial fibrillation.

INTRODUCTION: Focal Impulse and Rotor Modulation (FIRM) guided catheter ablation aiming at stable rotors has been investigated as a treatment option in patients with atrial fibrillation (AF). The objective of this study was to compare the safety and efficacy of FIRM-guided ablation with second-generation cryoballoon pulmonary vein isolation (CB2-PVI) in paroxysmal AF. METHODS: Consecutive patients (n = 22, mean age 60 ± 11 years, 59.1% of males) who were treated with a stand-alone FIRM-guided ablation were included in this retrospective single-center study. Procedural data and arrhythmia-free survival at 12 months were compared with n = 86 consecutive patients (mean age 62 ± 13 years, 62.4% of males) who received de-novo CB2-PVI. RESULTS: Median procedure duration was significantly longer in the FIRM group than in the CB2-PVI group (152 [IQR 120-176] minutes vs. 122 [110-145] minutes; p = .031). One patient (1.2%) in the CB2-PVI group and five patients (22.7%) in the FIRM group had vascular access complications. Atrial tachyarrhythmias recurred in 15 patients in the FIRM group and 11 in the CB2-PVI group. Kaplan-Meier estimation of single-procedure arrhythmia-free survival at 12 months was 25% (95% confidence interval [CI] 6%-44%) in the FIRM group and 87% (95% CI 78%-96%) in the CB2-PVI group (p < .001). Repeat ablations were performed in 14/20 (70.0%) patients in the FIRM group and in 12/85 (14.1%) in the CB2-PVI group (p < .001). CONCLUSION: De novo ablation of AF using FIRM-guided AF ablation results in shorter arrhythmia-free survival after 12 months compared to CB2-PVI and a need for repeat ablation in the majority of patients to achieve stable sinus rhythm.

Atrial appendage closure in patients with heart failure and atrial fibrillation: industry-independent single-centre study.

AIMS: To evaluate outcomes of percutaneous left atrial appendage closure (LAAC) in patients with congestive heart failure (CHF) and non-valvular atrial fibrillation (AF) in a consecutive, industry-independent registry associated with periprocedural success and complications during long-term follow-up. METHODS AND RESULTS: For this analysis, we included patients who underwent transcatheter LAAC from January 2014 to December 2019 at the University Heart Center in Lübeck, Germany, and compared patients with presence of CHF defined as patients with a reduced left ventricular ejection fraction (LVEF ≤ 40%), patients with a mid-range LVEF (LVEF 41-49%), patients with diastolic dysfunction and preserved LVEF (LVEF ≥ 50%), and patients with right-sided heart failure and impaired right ventricular function (tricuspid annular plane systolic excursion < 17) to patients undergoing LAAC with no CHF. Primary endpoints were defined as periprocedural complications, and complications during long-term follow-up presented as major adverse cardiac and cerebrovascular events (MACCE). A total of 300 consecutive patients underwent LAAC. Of these, 96 patients in the CHF group were compared with 204 patients in the non-CHF group. Implantation success was lower in CHF group in comparison with non-CHF group (99.5% vs. 96%, P = 0.038); otherwise, there were no differences in periprocedural complications between groups. Patients with CHF showed a significantly higher incidence of MACCE rate (31.9% vs. 15.1%, P = 0.002) and more deaths (24.2% vs. 7%, P ≤ 0.001) during long-term follow-up. In Cox multivariable regression analysis, CHF was an independent predictor of mortality after LAAC implantation at long-term follow-up (hazard ratio 3.23, 95% confidence intervals 1.52-6.86, P = 0.002). CONCLUSIONS: Implantation of LAAC devices in patients with non-valvular AF and CHF is safe. The increased mortality in patients with CHF compared with patients without CHF during the long-term follow-up is mainly attributed to comorbidities associated with CHF.

Individualized or fixed approach to pulmonary vein isolation utilizing the fourth-generation cryoballoon in patients with paroxysmal atrial fibrillation: the randomized INDI-FREEZE trial.

AIMS: Cryoballoon (CB) based pulmonary vein isolation (PVI) is a widely used technique for treatment of atrial fibrillation (AF); however the ideal energy dosing has not yet been standardized. This was a single-centre randomized clinical trial aiming at assessing the safety, acute efficacy, and clinical outcome of an individualized vs. a fixed CB ablation protocol using the fourth-generation CB (CB4) guided by pulmonary vein (PV) potential recordings and CB temperature. METHODS AND RESULTS: Patients were randomized in a 1:1 fashion to two different dosing protocols: INDI-FREEZE group (individualized protocol): freeze-cycle duration of time to effect plus 90 s or interruption of the freeze-cycle and repositioning CB if a CB temperature of -30°C was not within 40 s. Control group (fixed protocol): freeze-cycle duration of 180 s. No-bonus freeze-cycle was applied in either patient group. The primary endpoint was freedom from atrial tachyarrhythmia at 12 months. Secondary end points included procedural parameters and complications. A total of 100 patients with paroxysmal AF were prospectively enrolled. No difference was seen in the primary endpoint [INDI-FREEZE group: 38/47 (81%) vs. control group: 40/47, (85%), P = 0.583]. The total freezing time was significantly shorter in the INDI-FREEZE group (157 ± 56 s vs. 212 ± 83 s, P < 0.001), while procedure duration (57.9 ± 17.9 min vs. 63.2 ± 20.2 min, P = 0.172) was similar. No differences were seen in the minimum CB and oesophageal temperatures as well as in periprocedural complications. CONCLUSION: Compared to the fixed protocol, the individualized approach provides a similar safety profile and clinical outcome, while reducing the total freezing time.

Metabolic and Lipidomic Markers Differentiate COVID-19 From Non-Hospitalized and Other Intensive Care Patients.

Coronavirus disease 2019 (COVID-19) is a viral infection affecting multiple organ systems of great significance for metabolic processes. Thus, there is increasing interest in metabolic and lipoprotein signatures of the disease, and early analyses have demonstrated a metabolic pattern typical for atherosclerotic and hepatic damage in COVID-19 patients. However, it remains unclear whether this is specific for COVID-19 and whether the observed signature is caused by the disease or rather represents an underlying risk factor. To answer this question, we have analyzed 482 serum samples using nuclear magnetic resonance metabolomics, including longitudinally collected samples from 12 COVID-19 and 20 cardiogenic shock intensive care patients, samples from 18 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody-positive individuals, and single time point samples from 58 healthy controls. COVID-19 patients showed a distinct metabolic serum profile, including changes typical for severe dyslipidemia and a deeply altered metabolic status compared with healthy controls. Specifically, very-low-density lipoprotein and intermediate-density lipoprotein particles and associated apolipoprotein B and intermediate-density lipoprotein cholesterol were significantly increased, whereas cholesterol and apolipoprotein A2 were decreased. Moreover, a similarly perturbed profile was apparent when compared with other patients with cardiogenic shock who are in the intensive care unit when looking at a 1-week time course, highlighting close links between COVID-19 and lipid metabolism. The metabolic profile of COVID-19 patients distinguishes those from healthy controls and also from patients with cardiogenic shock. In contrast, anti-SARS-CoV-2 antibody-positive individuals without acute COVID-19 did not show a significantly perturbed metabolic profile compared with age- and sex-matched healthy controls, but SARS-CoV-2 antibody-titers correlated significantly with metabolic parameters, including levels of glycine, ApoA2, and small-sized low- and high-density lipoprotein subfractions. Our data suggest that COVID-19 is associated with dyslipidemia, which is not observed in anti-SARS-CoV-2 antibody-positive individuals who have not developed severe courses of the disease. This suggests that lipoprotein profiles may represent a confounding risk factor for COVID-19 with potential for patient stratification.

Comparison between Amulet and Watchman left atrial appendage closure devices: A real-world, single center experience.

BACKGROUND: Data reporting a head-to-head comparison between Amulet and Watchman devices are scarce. The aim of this study was to compare the Watchman™ versus Amulet™ left atrial appendage closure (LAAC) devices in a consecutive, industry-independent registry. METHODS: Patients who underwent LAAC using Watchman or Amulet devices from January 2014 to December 2019 at the University Heart Center Lübeck, Lübeck, Germany were included in the present analysis. Primary endpoints included periprocedural complications (in-hospital death, pericardial tamponade, device embolization, stroke, major bleeding and vascular access complications), and complications during long-term follow-up (ischemic stroke, hemorrhagic stroke, thromboembolism, device thrombus, bleeding and death). RESULTS: After matching the patients for age (±5 years), gender, CHA2DS2Vasc score (±1) and HASBLED score (±1), each of the Watchman and the Amulet groups included 113 patients. Patients in the Amulet group had significantly more periprocedural complications (2.7% vs 10.6%, p = 0.029; respectively) and more major bleeding complications (0% vs 5.3%, p = 0.029; respectively). During long-term follow-up, the rate of events was comparable between the Watchman and Amulet groups (18.3% versus 20.8%, p = 0.729; respectively). CONCLUSION: Amulet LAAC device was associated with increased periprocedural complications as compared to Watchman LAAC device. On long-term follow-up, both devices showed comparable efficacy and safety.

Comparison of risk prediction models in infarct-related cardiogenic shock.

AIMS: Several prediction models have been developed to allow accurate risk assessment and provide better treatment guidance in patients with infarct-related cardiogenic shock (CS). However, comparative data between these models are still scarce. The objective of the study is to externally validate different risk prediction models in infarct-related CS and compare their predictive value in the early clinical course. METHODS AND RESULTS: The Simplified Acute Physiology Score (SAPS) II Score, the CardShock score, the IABP-SHOCK II score, and the Society for Cardiovascular Angiography and Intervention (SCAI) classification were each externally validated in a total of 1055 patients with infarct-related CS enrolled into the randomized CULPRIT-SHOCK trial or the corresponding registry. The primary outcome was 30-day all-cause mortality. Discriminative power was assessed by comparing the area under the curves (AUC) in case of continuous scores. In direct comparison of the continuous scores in a total of 161 patients, the IABP-SHOCK II score revealed best discrimination [area under the curve (AUC = 0.74)], followed by the CardShock score (AUC = 0.69) and the SAPS II score, giving only moderate discrimination (AUC = 0.63). All of the three scores revealed acceptable calibration by Hosmer-Lemeshow test. The SCAI classification as a categorical predictive model displayed good prognostic assessment for the highest risk group (Stage E) but showed poor discrimination between Stages C and D with respect to short-term-mortality. CONCLUSION: Based on the present findings, the IABP-SHOCK II score appears to be the most suitable of the examined models for immediate risk prediction in infarct-related CS. Prospective evaluation of the models, further modification, or even development of new scores might be necessary to reach higher levels of discrimination.

Very high-power short-duration temperature-controlled ablation versus conventional power-controlled ablation for pulmonary vein isolation: The fast and furious - AF study.

BACKGROUND: Catheter ablation for atrial fibrillation (AF) treatment provides effective and durable pulmonary vein isolation (PVI) and is associated with encouraging clinical outcome. A novel CF sensing temperature-controlled radiofrequency (RF) ablation catheter allows for very high-power short-duration (vHP-SD, 90 W/4 s) ablation aiming a potentially safer, more effective and faster ablation. We thought to evaluate preliminary safety and efficacy of vHP-SD ablation for PVI utilizing a novel vHP-SD catheter. The data was compared to conventional power-controlled ablation index (AI) guided PVI utilizing conventional contact force (CF) sensing catheters. METHODS AND RESULTS: Fifty-six patients with paroxysmal or persistent AF were prospectively enrolled in this study. Twenty-eight consecutive patients underwent vHP-SD based PVI (vHP-SD group) and were compared to 28 consecutive patients treated with conventional CF-sensing catheters utilizing the AI (control group). All PVs were successfully isolated using vHP-SD. The median RF ablation time for vHP-SD was 338 (IQR 286, 367) seconds vs control 1580 (IQR 1350, 1848) seconds (p < 0.0001), the median procedure duration was vHP-SD 55 (IQR 48-60) minutes vs. control 105 (IQR 92-120) minutes (p < 0.0001). No differences in periprocedural complications were observed. CONCLUSIONS: This preliminary data of the novel vHP-SD ablation mode provides safe and effective PVI. Procedure duration and RF ablation time were substantially shorter in the vHP-SD group in comparison to the control group.

Safety and Efficacy of Cryoballoon Based Pulmonary Vein Isolation in Patients with Atrial Fibrillation and a History of Cancer.

INTRODUCTION: A growing body of evidence suggests a strong association between atrial fibrillation (AF) and cancer. A relevant number of patients with a present or former malignant disease with highly symptomatic drug-refractory AF are in need of interventional therapy. Data on the safety and efficacy of catheter ablation in these patients are sparse. The present study aims to analyze the safety and efficacy of cryoballoon-based pulmonary vein isolation (CB-PVI) for symptomatic AF in patients with past or present cancer disease. METHODS AND RESULTS: Consecutive patients undergoing CB-PVI for symptomatic AF at University Hospital Lübeck, Germany between July 2015 and January 2019 were included in this study. Propensity-score based matching was performed to identify comparable patients with and without cancer disease and further analyze clinical characteristics, periprocedural complications and arrhythmia-free survival. A total of 70 patients with a history of cancer undergoing CB-PVI were matched to 70 patients without a history of cancer. The frequency of complications was similar between patients with and without a history of cancer (p = 0.11), with four phrenic nerve palsies occurring in patients with a history of cancer (5.6% of the cohort) vs. one phrenic nerve palsy in patients without cancer (p = 0.36). Arrhythmia free survival after 12 months did not differ significantly in patients with and without a history of cancer (67.1 ± 5.8% vs. 77.8% ± 5.1%, p = 0.16). CONCLUSION: This study indicates that CB-PVI for symptomatic AF is equally safe and effective in patients with and without a history of cancer and cancer treatment.

The C5a/C5a receptor 1 axis controls tissue neovascularization through CXCL4 release from platelets.

Platelets contribute to the regulation of tissue neovascularization, although the specific factors underlying this function are unknown. Here, we identified the complement anaphylatoxin C5a-mediated activation of C5a receptor 1 (C5aR1) on platelets as a negative regulatory mechanism of vessel formation. We showed that platelets expressing C5aR1 exert an inhibitory effect on endothelial cell functions such as migration and 2D and 3D tube formation. Growth factor- and hypoxia-driven vascularization was markedly increased in C5ar1-/- mice. Platelet-specific deletion of C5aR1 resulted in a proangiogenic phenotype with increased collateralization, capillarization and improved pericyte coverage. Mechanistically, we found that C5a induced preferential release of CXC chemokine ligand 4 (CXCL4, PF4) from platelets as an important antiangiogenic paracrine effector molecule. Interfering with the C5aR1-CXCL4 axis reversed the antiangiogenic effect of platelets both in vitro and in vivo.In conclusion, we identified a mechanism for the control of tissue neovascularization through C5a/C5aR1 axis activation in platelets and subsequent induction of the antiangiogenic factor CXCL4.

Novel Cryoballoon Ablation System for Single Shot Pulmonary Vein Isolation　- The Prospective ICE-AGE-X Study.

BACKGROUND: The arctic front cryoballoon (AF-CB) provides effective and durable pulmonary vein isolation (PVI) associated with encouraging clinical outcome. The POLARx cryoballoon incorporates unique features and design changes that may translate into improved efficacy, safety and further simplified balloon-based procedures. Efficacy and safety of the novel POLARx cryoballoon was compared to the fourth generation AF-CB (AF-CB4).Methods and Results:Twenty-five consecutive patients with paroxysmal or persistent atrial fibrillation were prospectively enrolled, underwent POLARx-based PVI (POLARx group) and were compared to 25 consecutive patients treated with the AF-CB4 (AF-CB4 group). All PVs were successfully isolated utilizing the POLARx and AF-CB4. A significant difference regarding the mean minimal cryoballoon temperatures reached using the AF-CB4 and POLARx (-50±6℃ vs. -57±7℃, P=0.004) was observed. Real-time PVI was visualized in 81% of POLARx patients and 42% of AF-CB4 patients (P<0.001). Utilizing the POLARx, a trend towards shorter median procedure time (POLARx: 45 [39, 53] min vs. AF-CB4: 55 [50, 60] min; P=0.062) was found. No differences were observed between AF-CB4 and POLARx concerning catheter maneuverability, catheter stability and periprocedural complications. CONCLUSIONS: The novel POLARx showed similar safety and efficacy compared to the AF-CB4. A higher rate of real-time PV recordings and significantly lower minimal balloon temperatures were observed using the POLARx.

Impact of Anesthesia Strategy and Valve Type on Clinical Outcomes After Transcatheter Aortic Valve Replacement.

BACKGROUND: The randomized SOLVE-TAVI (compariSon of secOnd-generation seLf-expandable vs. balloon-expandable Valves and gEneral vs. local anesthesia in Transcatheter Aortic Valve Implantation) trial compared newer-generation self-expanding valves (SEV) and balloon-expandable valves (BEV) as well as local anesthesia with conscious sedation (CS) and general anesthesia (GA) in patients undergoing transfemoral transcatheter aortic valve replacement (TAVR). Both strategies showed similar outcomes at 30 days. OBJECTIVES: The purpose of this study was to compare clinical outcomes during 1-year follow-up in the randomized SOLVE-TAVI trial. METHODS: Using a 2 × 2 factorial design 447 intermediate- to high-risk patients with severe, symptomatic aortic stenosis were randomly assigned to transfemoral TAVR using either the SEV (Evolut R, Medtronic Inc., Minneapolis, Minnesota) or the BEV (Sapien 3, Edwards Lifesciences, Irvine, California) as well as CS or GA at 7 sites. RESULTS: In the valve-comparison strategy, rates of the combined endpoint of all-cause mortality, stroke, moderate or severe paravalvular leakage, and permanent pacemaker implantation were similar between the BEV and SEV group (n = 84, 38.3% vs. n = 87, 40.4%; hazard ratio: 0.94; 95% confidence interval: 0.70 to 1.26; p = 0.66) at 1 year. Regarding the anesthesia comparison, the combined endpoint of all-cause mortality, stroke, myocardial infarction, and acute kidney injury occurred with similar rates in the GA and CS groups (n = 61, 25.7% vs. n = 54, 23.8%; hazard ratio: 1.09; 95% confidence interval: 0.76 to 1.57; p = 0.63). CONCLUSIONS: In intermediate- to high-risk patients undergoing transfemoral TAVR, newer-generation SEV and BEV as well as CS and GA showed similar clinical outcomes at 1 year using a combined clinical endpoint. (SecOnd-generation seLf-expandable Versus Balloon-expandable Valves and gEneral Versus Local Anesthesia in TAVI [SOLVE-TAVI]; NCT02737150).

Impact of Morphine Treatment With and Without Metoclopramide Coadministration on Myocardial and Microvascular Injury in Acute Myocardial Infarction: Insights From the Randomized MonAMI Trial.

Background Intravenous morphine administration can adversely affect platelet inhibition induced by P2Y12 receptor inhibitors after acute myocardial infarction. In contrast, some evidence suggests that opioid agonists may have cardioprotective effects on the myocardium. The aim of this prospective, randomized MonAMI (Impact of Morphine Treatment With and Without Metoclopramide Coadministration on Platelet Inhibition in Acute Myocardial Infarction) trial was, therefore, to investigate the impact of morphine with or without metoclopramide coadministration on myocardial and microvascular injury. Methods and Results Patients with acute myocardial infarction (n=138) were assigned in a 1:1:1 ratio to ticagrelor 180 mg plus: (1) intravenous morphine 5 mg (morphine group); (2) intravenous morphine 5 mg and metoclopramide 10 mg (morphine+metoclopramide group); or (3) intravenous placebo (control group) administered before primary percutaneous coronary intervention. Cardiac magnetic resonance imaging was performed in 104 patients on day 1 to 4 after the index event. Infarct size was significantly smaller in the morphine only group as compared with controls (percentage of left ventricular mass, 15.5 versus 17.9; P=0.047). Furthermore, the number of patients with microvascular obstruction was significantly lower after morphine administration (28% versus 54%; P=0.022) and the extent of microvascular obstruction was smaller (percentage of left ventricular mass, 0 versus 0.74; P=0.037). In multivariable regression analysis, morphine administration was independently associated with a reduced risk for the occurrence of microvascular obstruction (odds ratio, 0.37; 95% CI, 0.14-0.93 [P=0.035]). There was no significant difference in infarct size (P=0.491) and extent (P=0.753) or presence (P=0.914) of microvascular obstruction when comparing the morphine+metoclopramide group with the control group. Conclusions In this randomized study, intravenous administration of morphine before primary percutaneous coronary intervention resulted in a significant reduction of myocardial and microvascular damage following acute myocardial infarction. This effect was not observed in the morphine plus metoclopramide group. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02627950.

Experience and procedural efficacy of pulmonary vein isolation using the fourth and second generation cryoballoon: The shorter, the better?

BACKGROUND: The second-generation cryoballoon (CB2) provides effective and durable pulmonary vein isolation (PVI) associated with encouraging clinical outcome. The novel fourth-generation cryoballoon (CB4) incorporates a 40% shorter distal tip. This design change may translate into an increased rate of PVI real-time signal recording, facilitating an individualized ablation strategy using the time to effect (TTE). METHODS AND RESULTS: Three hundred consecutive patients with paroxysmal or persistent atrial fibrillation were prospectively enrolled. The first 150 consecutive patients underwent CB2 based PVI (CB2 group) and the last 150 consecutive patients were treated with the CB4 (CB4 group). A total of 594/594 (100%, CB4) and 589/594 (99.2%, CB2) pulmonary veins (PVs) were successfully isolated utilizing the CB4 and CB2, respectively (p = .283). The real-time PVI visualization rate was 47% (CB4) and 39% (CB2; p = .005) and the mean freeze cycle duration 200 ± 90 s (CB4) and 228 ± 110 s (CB2; p < .001), respectively. The total procedure time did not differ between the groups (CB4: 64 ± 32 min) and (CB2: 62 ± 29 min, p = .370). No differences in periprocedural complications were detected. CONCLUSIONS: A higher rate of real-time electrical PV recordings are seen using the CB4 as compared to CB2, which may facilitate an individualized ablation strategy using the TTE.

New technologies for intensive prevention programs after myocardial infarction: rationale and design of the NET-IPP trial.

INTRODUCTION: Current health care data reveal suboptimal prevention in patients with coronary artery disease and an unmet need to develop effective preventive strategies. The New Technologies for Intensive Prevention Programs (NET-IPP) Trial will investigate if a long-term web-based prevention program after myocardial infarction (MI) will reduce clinical events and risk factors. In a genetic sub study the impact of disclosure of genetic risk using polygenic risk scores (PRS) will be assessed. STUDY DESIGN: Patients hospitalized for MI will be prospectively enrolled and assigned to either a 12-months web-based intensive prevention program or standard care. The web-based program will include telemetric transmission of risk factor data, e-learning and electronic contacts between a prevention assistant and the patients. The combined primary study endpoint will comprise severe adverse cardiovascular events after 2 years. Secondary endpoints will be risk factor control, adherence to medication and quality of life. In a genetic sub study genetic risk will be assessed in all patients of the web-based intensive prevention program group by PRS and patients will be randomly assigned to genetic risk disclosure vs. no disclosure. The study question will be if disclosure of genetic risk has an impact on patient motivation and cardiovascular risk factor control. CONCLUSIONS: The randomized multicenter NET-IPP study will evaluate for the first time the effects of a long-term web-based prevention program after MI on clinical events and risk factor control. In a genetic sub study the impact of disclosure of genetic risk using PRS will be investigated.

General Versus Local Anesthesia With Conscious Sedation in Transcatheter Aortic Valve Implantation: The Randomized SOLVE-TAVI Trial.

BACKGROUND: In clinical practice, local anesthesia with conscious sedation (CS) is performed in roughly 50% of patients undergoing transcatheter aortic valve replacement. However, no randomized data assessing the safety and efficacy of CS versus general anesthesia (GA) are available. METHODS: The SOLVE-TAVI (Comparison of Second-Generation Self-Expandable Versus Balloon-Expandable Valves and General Versus Local Anesthesia in Transcatheter Aortic Valve Implantation) trial is a multicenter, open-label, 2×2 factorial, randomized trial of 447 patients with aortic stenosis undergoing transfemoral transcatheter aortic valve replacement comparing CS versus GA. The primary efficacy end point was powered for equivalence (equivalence margin 10% with significance level 0.05) and consisted of the composite of all-cause mortality, stroke, myocardial infarction, infection requiring antibiotic treatment, and acute kidney injury at 30 days. RESULTS: The primary composite end point occurred in 27.2% of CS and 26.4% of GA patients (rate difference, 0.8 [90% CI, -6.2 to 7.8]; Pequivalence=0.015). Event rates for the individual components were as follows: all-cause mortality, 3.2% versus 2.3% (rate difference, 1.0 [90% CI, -2.9 to 4.8]; Pequivalence<0.001); stroke, 2.4% versus 2.8% (rate difference, -0.4 [90% CI, -3.8 to 3.8]; Pequivalence<0.001); myocardial infarction, 0.5% versus 0.0% (rate difference, 0.5 [90% CI, -3.0 to 3.9]; Pequivalence<0.001), infection requiring antibiotics 21.1% versus 22.0% (rate difference, -0.9 [90% CI, -7.5 to 5.7]; Pequivalence=0.011); acute kidney injury, 9.0% versus 9.2% (rate difference, -0.2 [90% CI, -5.2 to 4.8]; Pequivalence=0.0005). There was a lower need for inotropes or vasopressors with CS (62.8%) versus GA (97.3%; rate difference, -34.4 [90% CI, -41.0 to -27.8]). CONCLUSIONS: Among patients with aortic stenosis undergoing transfemoral transcatheter aortic valve replacement, use of CS compared with GA resulted in similar outcomes for the primary efficacy end point. These findings suggest that CS can be safely applied for transcatheter aortic valve replacement. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02737150.

In vitro comparison of everting vs. non-everting suture techniques for the implantation of a supra-annular biological heart valve.

BACKGROUND: The aim of this study was to evaluate the hemodynamic effect of different suturing techniques for aortic valve replacement (AVR) in vitro. Whether or not the applied suturing technique impacts the outflow tract diameter by narrowing the annulus diameter was examined. METHODS: The commonly applied non-everting pledget forced suture technique (NE, n=13) was compared with an everting pledget forced suture (ET, n=13) for AVR using the 25 mm St. Jude Trifecta aortic valve. Hemodynamic parameters were obtained in a pulsatile flow simulator. A high speed camera captured the visual aspects of the suturing technique. RESULTS: Despite some kind of left ventricular outflow narrowing due to protruding pledgets using the NE suture technique, mean pressure gradients of both techniques were nearly similar (NE 5.88±2.7 mmHg, ET 5.23±1.31 mmHg, P=0.44). Closing volume (NE 3.16±0.48 mL; ET 3.51±0.68 mL; P=0.14) and the leakage volume (NE: 8.09±2.53 mL; ET: 8.35±3.65 mL; P=0.83) also showed no differences. CONCLUSIONS: AVR using either suturing techniques leads to a similar hemodynamic performance in vitro. The impact of the suturing technique may be higher in a smaller annulus. Therefore, further studies using smaller prostheses are necessary.