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).

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.

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.

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.

Rapid pulmonary vein isolation utilizing the third-generation laserballoon - The PhoeniX registry.

BACKGROUND: Balloon-based ablation systems for pulmonary vein isolation (PVI) are providing procedural safety and efficacy as well as favourable clinical outcome. Although second-generation laser balloon (LB2) based PVI has been shown safety and efficacy relatively long procedural duration was a strong limitation. The third-generation laser balloon (LB3) offers and automized ablation for rapid PVI. We determined safety, efficacy and procedural characteristics of this new promising ablation system. METHODS AND RESULTS: A total of 15 consecutive patients were prospectively enrolled. All patients underwent PVI using the LB3. A total 59/59 PVs (100%) were successfully isolated. Procedural data was compared to the last 15 consecutive patients treated by the LB2. The median procedure time significantly declined from LB2 (91 (86, 105) min) to LB3 (77 (68, 87) min), p < 0.001. Similarly, the median left atrial dwelling time significantly decreased from LB2 (72 (62, 84) min) to LB3 (45 (38, 52) min), p < 0.0001. The total laser time decreased from LB2 (1920 (1765, 2193) sec) to LB3 (1077 (896, 1165) sec), p < 0.00001. A pure single shot PVI was performed in 18/59 PVs (31%). For major adverse events no differences were detected between the groups (LB2 1/15 (6.7%) and LB3 1/15 (6.7%), p = 0.999). CONCLUSION: The LB3 was safe and effective for PVI. Procedure time, LA dwelling time and total laser time significantly decreased compared to LB2.

Frequency and Impact of Bleeding on Outcome in Patients With Cardiogenic Shock.

OBJECTIVES: This study sought to determine frequency, associated factors, and impact of bleeding in infarct-related cardiogenic shock. BACKGROUND: Early revascularization is associated with improved survival in patients with acute myocardial infarction complicated by cardiogenic shock. On the downside, invasive treatment and accompanying antithrombotic therapies are associated with an increased bleeding risk. Prospective data assessing the incidence, severity, risk factors, and prognostic implication of bleeding in patients with cardiogenic shock are scarce. METHODS: As a pre-defined subanalysis of the CULPRIT-SHOCK (PCI Strategies in Patients with Acute Myocardial Infarction and Cardiogenic Shock) randomized trial, we examined distribution of bleeding events in 684 patients with infarct-related cardiogenic shock and compared patients with any bleeding to those without. RESULTS: A total of 21.5% patients experienced at least 1 bleeding event until 30 days after randomization. The vast majority of bleeding (57%) occurred within the first 2 days of hospitalization. Patients with bleeding had prolonged catecholamine treatment and mechanical ventilation and there was a significant association with sepsis, peripheral ischemic complications, new atrial fibrillation, and ventricular fibrillation. In multivariable analysis, bleeding was associated with a significantly higher mortality (hazard ratio: 2.11; 95% confidence interval: 1.63 to 2.75; p < 0.0001). Treatment with active mechanical support by extracorporeal membrane oxygenation or Impella emerged as the major risk factor for bleeding. CONCLUSIONS: Risk of bleeding in infarct-related cardiogenic shock is high and associated with increased mortality.

Sex-Specific Management in Patients With Acute Myocardial Infarction and Cardiogenic Shock: A Substudy of the CULPRIT-SHOCK Trial.

BACKGROUND: Women are more likely to suffer and die from cardiogenic shock (CS) as the most severe complication of acute myocardial infarction. Data concerning optimal management for women with CS are scarce. Aim of this study was to better define characteristics of women experiencing CS and to the influence of sex on different treatment strategies. METHODS: In the CULPRIT-SHOCK trial (The Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock), patients with CS complicating acute myocardial infarction and multivessel coronary artery disease were randomly assigned to one of the following revascularization strategies: either percutaneous coronary intervention of the culprit-lesion-only or immediate multivessel percutaneous coronary intervention. Primary end point was composite of death from any cause or severe renal failure leading to renal replacement therapy within 30 days. We investigated sex-specific differences in general and according to the revascularization strategies. RESULTS: Among all 686 randomized patients included in the analysis, 24% were women. Women were older and had more often diabetes mellitus and renal insufficiency, whereas they had less often history of previous acute myocardial infarction and smoking. After 30 days, the primary clinical end point was not significantly different between groups (56% women versus 49% men; odds ratio, 1.29 [95% CI, 0.91-1.84]; P=0.15). There was no interaction between sex and coronary revascularization strategy regarding mortality and renal failure (Pinteraction=0.11). The primary end point occurred in 56% of women treated by the culprit-lesion-only strategy versus 42% men, whereas 55% of women and 55% of men in the multivessel percutaneous coronary intervention group. CONCLUSIONS: Although women presented with a different risk profile, mortality and renal replacement were similar to men. Sex did not influence mortality and renal failure according to the different coronary revascularization strategies. Based on these data, women and men presenting with CS complicating acute myocardial infarction and multivessel coronary artery disease should not be treated differently. However, further randomized trials powered to address potential sex-specific differences in CS are still necessary. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01927549.

Long-term outcome after thrombus aspiration in non-ST-elevation myocardial infarction: results from the TATORT-NSTEMI trial : Thrombus aspiration in acute myocardial infarction.

AIMS: To investigate the long-term prognostic value of aspiration thrombectomy in conjunction with primary percutaneous coronary intervention (PCI) compared to conventional PCI in patients with non-ST-elevation myocardial infarction (NSTEMI). METHODS: In the randomized TATORT-NSTEMI (Thrombus aspiration in thrombus containing culprit lesions in non-ST-elevation myocardial infarction) trial, NSTEMI patients with thrombus containing culprit lesions were randomized to either PCI with aspiration thrombectomy or conventional PCI. The endpoint was a combination of all-cause death, reinfarction and new congestive heart failure. RESULTS: From 440 patients initially randomized, outcome data were available in 432 (98.2%) patients at a median follow-up of 4.9 (interquartile range [IQR] 4.4-5.0) years. Thrombectomy was associated with a significant reduction of the combined endpoint compared to conventional PCI (19.9% vs. 30.7%, p = 0.01). This finding was primarily driven by a reduced rate of reinfarction with thrombectomy (3.4% vs. 10.3%, p = 0.01). Thrombectomy was still independently associated with the combined endpoint after multivariable adjustment (hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.30-0.76, p = 0.002). Findings were consistent across all analyzed subgroups (p values for interaction all > 0.05). CONCLUSIONS: In NSTEMI, thrombus aspiration is associated with favorable clinical outcome during long-term follow-up. CLINICAL TRIAL REGISTRATION: NCT01612312.

Comparison of newer generation self-expandable vs. balloon-expandable valves in transcatheter aortic valve implantation: the randomized SOLVE-TAVI trial.

AIMS: Transcatheter aortic valve implantation (TAVI) has emerged as established treatment option in patients with symptomatic aortic stenosis. Technical developments in valve design have addressed previous limitations such as suboptimal deployment, conduction disturbances, and paravalvular leakage. However, there are only limited data available for the comparison of newer generation self-expandable valve (SEV) and balloon-expandable valve (BEV). METHODS AND RESULTS: SOLVE-TAVI is a multicentre, open-label, 2 × 2 factorial, randomized trial of 447 patients with aortic stenosis undergoing transfemoral TAVI comparing SEV (Evolut R, Medtronic Inc., Minneapolis, MN, USA) with BEV (Sapien 3, Edwards Lifesciences, Irvine, CA, USA). The primary efficacy composite endpoint of all-cause mortality, stroke, moderate/severe prosthetic valve regurgitation, and permanent pacemaker implantation at 30 days was powered for equivalence (equivalence margin 10% with significance level 0.05). The primary composite endpoint occurred in 28.4% of SEV patients and 26.1% of BEV patients meeting the prespecified criteria of equivalence [rate difference -2.39 (90% confidence interval, CI -9.45 to 4.66); Pequivalence = 0.04]. Event rates for the individual components were as follows: all-cause mortality 3.2% vs. 2.3% [rate difference -0.93 (90% CI -4.78 to 2.92); Pequivalence < 0.001], stroke 0.5% vs. 4.7% [rate difference 4.20 (90% CI 0.12 to 8.27); Pequivalence = 0.003], moderate/severe paravalvular leak 3.4% vs. 1.5% [rate difference -1.89 (90% CI -5.86 to 2.08); Pequivalence = 0.0001], and permanent pacemaker implantation 23.0% vs. 19.2% [rate difference -3.85 (90% CI -10.41 to 2.72) in SEV vs. BEV patients; Pequivalence = 0.06]. CONCLUSION: In patients with aortic stenosis undergoing transfemoral TAVI, newer generation SEV and BEV are equivalent for the primary valve-related efficacy endpoint. These findings support the safe application of these newer generation percutaneous valves in the majority of patients with some specific preferences based on individual valve anatomy.