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.

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.

One-Year Outcomes after PCI Strategies in Cardiogenic Shock.

BACKGROUND: Among patients with acute myocardial infarction, cardiogenic shock, and multivessel coronary artery disease, the risk of a composite of death from any cause or severe renal failure leading to renal-replacement therapy at 30 days was found to be lower with percutaneous coronary intervention (PCI) of the culprit lesion only than with immediate multivessel PCI. We evaluated clinical outcomes at 1 year. METHODS: We randomly assigned 706 patients to either culprit-lesion-only PCI or immediate multivessel PCI. The results for the primary end point of death or renal-replacement therapy at 30 days have been reported previously. Prespecified secondary end points at 1 year included death from any cause, recurrent myocardial infarction, repeat revascularization, rehospitalization for congestive heart failure, the composite of death or recurrent infarction, and the composite of death, recurrent infarction, or rehospitalization for heart failure. RESULTS: As reported previously, at 30 days, the primary end point had occurred in 45.9% of the patients in the culprit-lesion-only PCI group and in 55.4% in the multivessel PCI group (P=0.01). At 1 year, death had occurred in 172 of 344 patients (50.0%) in the culprit-lesion-only PCI group and in 194 of 341 patients (56.9%) in the multivessel PCI group (relative risk, 0.88; 95% confidence interval [CI], 0.76 to 1.01). The rate of recurrent infarction was 1.7% with culprit-lesion-only PCI and 2.1% with multivessel PCI (relative risk, 0.85; 95% CI, 0.29 to 2.50), and the rate of a composite of death or recurrent infarction was 50.9% and 58.4%, respectively (relative risk, 0.87; 95% CI, 0.76 to 1.00). Repeat revascularization occurred more frequently with culprit-lesion-only PCI than with multivessel PCI (in 32.3% of the patients vs. 9.4%; relative risk, 3.44; 95% CI, 2.39 to 4.95), as did rehospitalization for heart failure (5.2% vs. 1.2%; relative risk, 4.46; 95% CI, 1.53 to 13.04). CONCLUSIONS: Among patients with acute myocardial infarction and cardiogenic shock, the risk of death or renal-replacement therapy at 30 days was lower with culprit-lesion-only PCI than with immediate multivessel PCI, and mortality did not differ significantly between the two groups at 1 year of follow-up. (Funded by the European Union Seventh Framework Program and others; CULPRIT-SHOCK ClinicalTrials.gov number, NCT01927549 .).

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.

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.

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.

Intraaortic Balloon Pump in Cardiogenic Shock Complicating Acute Myocardial Infarction: Long-Term 6-Year Outcome of the Randomized IABP-SHOCK II Trial.

BACKGROUND: The role of intraaortic balloon counterpulsation (IABP) in cardiogenic shock is still a subject of intense debate despite the neutral results of the IABP-SHOCK II trial (Intraaortic Balloon Pump in Cardiogenic Shock II) with subsequent downgrading in international guidelines. So far, randomized data on the impact of IABP on long-term clinical outcomes in patients with cardiogenic shock complicating acute myocardial infarction are lacking. Furthermore, only limited evidence is available on general long-term outcomes of patients with cardiogenic shock treated by contemporary practice. METHODS: The IABP-SHOCK II trial is a multicenter, randomized, open-label trial. Between 2009 and 2012, 600 patients with cardiogenic shock complicating acute myocardial infarction undergoing early revascularization were randomized to IABP versus control. RESULTS: Long-term follow-up was performed 6.2 years (interquartile range 5.6-6.7) after initial randomization. Follow-up was completed for 591 of 600 patients (98.5%). Mortality was not different between the IABP and the control group (66.3% versus 67.0%; relative risk, 0.99; 95% CI, 0.88-1.11; P=0.98). There were also no differences in recurrent myocardial infarction, stroke, repeat revascularization, or rehospitalization for cardiac reasons (all P>0.05). Survivors' quality of life as assessed by the EuroQol 5D questionnaire and the New York Heart Association class did not differ between groups. CONCLUSIONS: IABP has no effect on all-cause mortality at 6-year long-term follow-up. Mortality is still very high, with two thirds of patients with cardiogenic shock dying despite contemporary treatment with revascularization therapy. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov/. Unique identifier: NCT00491036.

PCI Strategies in Patients with Acute Myocardial Infarction and Cardiogenic Shock.

BACKGROUND: In patients who have acute myocardial infarction with cardiogenic shock, early revascularization of the culprit artery by means of percutaneous coronary intervention (PCI) improves outcomes. However, the majority of patients with cardiogenic shock have multivessel disease, and whether PCI should be performed immediately for stenoses in nonculprit arteries is controversial. METHODS: In this multicenter trial, we randomly assigned 706 patients who had multivessel disease, acute myocardial infarction, and cardiogenic shock to one of two initial revascularization strategies: either PCI of the culprit lesion only, with the option of staged revascularization of nonculprit lesions, or immediate multivessel PCI. The primary end point was a composite of death or severe renal failure leading to renal-replacement therapy within 30 days after randomization. Safety end points included bleeding and stroke. RESULTS: At 30 days, the composite primary end point of death or renal-replacement therapy had occurred in 158 of the 344 patients (45.9%) in the culprit-lesion-only PCI group and in 189 of the 341 patients (55.4%) in the multivessel PCI group (relative risk, 0.83; 95% confidence interval [CI], 0.71 to 0.96; P=0.01). The relative risk of death in the culprit-lesion-only PCI group as compared with the multivessel PCI group was 0.84 (95% CI, 0.72 to 0.98; P=0.03), and the relative risk of renal-replacement therapy was 0.71 (95% CI, 0.49 to 1.03; P=0.07). The time to hemodynamic stabilization, the risk of catecholamine therapy and the duration of such therapy, the levels of troponin T and creatine kinase, and the rates of bleeding and stroke did not differ significantly between the two groups. CONCLUSIONS: Among patients who had multivessel coronary artery disease and acute myocardial infarction with cardiogenic shock, the 30-day risk of a composite of death or severe renal failure leading to renal-replacement therapy was lower among those who initially underwent PCI of the culprit lesion only than among those who underwent immediate multivessel PCI. (Funded by the European Union 7th Framework Program and others; CULPRIT-SHOCK ClinicalTrials.gov number, NCT01927549 .).

Impact of transcatheter mitral valve repair on ventricular arrhythmias.

AIMS: Patients with heart failure and severe mitral regurgitation (MR) have a poor prognosis and carry an increased risk for ventricular arrhythmias. The present study evaluates the impact of transcatheter mitral valve repair using the MitraClip on the potential reduction of ventricular arrhythmias. METHODS AND RESULTS: Patients undergoing MitraClip implantation were prospectively enrolled into the present study and received 24 h Holter ECG assessment prior to and 6 months after the procedure. In addition, left ventricular dimensions and function were assessed at baseline and follow-up. A total of 50 patients with mainly functional MR (82%) were included. Non-sustained or sustained ventricular tachycardia (nsVT and/or sVT) occurred in 32% of patients and was reduced to 14% at follow-up (P = 0.01). Also, premature ventricular complex (PVC) burden ≥5% decreased from 16% to 4% (P = 0.04). Patients with persistent (n = 6) or new (n = 1) nsVT and/or sVT at follow-up showed a significant decrease in left ventricular ejection fraction from 38% (interquartile range 26-45%) to 33% (interquartile range 22-44%; P = 0.03). CONCLUSIONS: In this prospective study, transcatheter mitral valve repair using MitraClip was associated with a reduced prevalence of ventricular arrhythmias. The subset of patients with persistent or new ventricular arrhythmias after MitraClip implantation showed progression of left ventricular dysfunction.

Second-Generation Visually Guided Laser Balloon Ablation System for Pulmonary Vein Isolation: Learning Curve, Safety and Efficacy　- The MERLIN Registry.

BACKGROUND: Radiofrequency (RF)-based pulmonary vein isolation (PVI) results in a favorable clinical outcome, although its complexity demands a long learning curve. Balloon-based systems have been developed to possibly solve these limitations. The 2nd-generation laser balloon (LB2) offers optimized features for improved tissue contact and visibility. We determined the safety, efficacy and learning curve of the LB2 for PVI.Methods and Results:A total of 45 consecutive patients (89% persistent AF) were prospectively enrolled and divided into 3 groups (T1, T2, T3) of n=15 patients per group. All patients underwent PVI by 2 operators using the LB2. The operators were experienced in RF and cryothermal procedures, but not in laser ablations. A total of 174/177 PVs (98%) were successfully isolated. The median procedure time significantly declined from 132 (114, 158) to 119 (102, 127) and 91 (86, 105) min in T1-3, respectively (P=0.0009). Similarly, the median fluoroscopy time significantly decreased from T1 to T3 (22 (17, 27) vs. 21 (16, 24) vs. 13 (10, 17) min, respectively, P=0.045). Adverse events occurred in 6.7%, with a trend towards a lower complication rate with increasing experience. CONCLUSIONS: The LB2 was safe and effective for PVI, even for operators without any previous experience in laser balloon-based PVI. Procedure time, left atrial dwelling time and fluoroscopy time decreased after a learning curve of 15 cases.

Efficacy and Safety of Cryoballoon Ablation in Patients With Heart Failure and Reduced Left Ventricular Ejection Fraction　- A Multicenter Study.

BACKGROUND: Second-generation cryoballoon (CB2)-based pulmonary vein isolation (PVI) has demonstrated encouraging results in the treatment of atrial fibrillation (AF). This study sought to assess data on the safety, efficacy and clinical success of CB2-based PVI in patients with heart failure (HF) and reduced ejection fraction (HFrEF).Methods and Results:CB2-based PVI was performed in 551 consecutive patients in 3 highly experienced EP centers. Patients with HF and LVEF ≤40% were included (HFrEF group, n=50/551, 9.1%). Data were compared with propensity score-matched patients without HF and preserved left ventricular EF (LVEF) (n=50, control group). The median LVEF was HFrEF: 37% (35, 40) and control: 55% (55, 55), P<0.0001. Major periprocedural complications were registered in 4/50 (8%, HFrEF group) and 3/50 (6%, control group), P=0.695. The 12-month freedom from AF recurrence was 73.1% (95% confidence interval (CI): 61-88, HFrEF group) and 72.6% (95% CI: 61-87, control group), P=0.25. NYHA class decreased from 2.4±0.8 (baseline) to 1.7±0.8 at 12-month follow-up (P<0.0001). LVEF improved from a median of 37% (35, 40) prior to ablation to a median of 55% (40, 55), P<0.0001. CONCLUSIONS: CB2-based PVI in patients with HFrEF appeared to be safe, was associated with comparable periprocedural complications and showed promising clinical success rates equal to those for patients with preserved LVEF. NYHA class and LVEF significantly improved at 12-month follow-up.

Does Undersizing of Transcatheter Aortic Valve Bioprostheses during Valve-in-Valve Implantation Avoid Coronary Obstruction? An In Vitro Study.

Background The transcatheter aortic valve-in-valve implantation (TAViVI) is an evolving treatment strategy for degenerated surgical aortic valve bioprostheses (SAVBs) in patients with high operative risk. Although hemodynamics is excellent, there is some concern regarding coronary obstruction, especially in SAVB with externally mounted leaflet tissue, such as the Trifecta (St. Jude Medical Inc., St. Paul, Minnesota, United States). We investigated coronary flow and hydrodynamics before and after TAViVI in a SAVB with externally mounted leaflet tissue (St. Jude Medical, Trifecta) with an undersized transcatheter aortic valve bioprosthesis (Edwards Sapien XT; Edwards Lifesciences LLC, Irvine, California, United States) in an in vitro study. Materials and Methods An aortic root model was constructed incorporating geometric dimensions known as risk factors for coronary obstruction. Investigating the validity of this model, we primarily performed recommended TAViVI with the Sapien XT (size 26 mm) in a Trifecta (size 25 mm) in a mock circulation. Thereafter, hydrodynamic performance and coronary flow (left/right coronary diastolic flow [lCF/rCF]) after TAViVI with an undersized Sapien XT (size 23 mm) in a Trifecta (size 25 mm) were investigated at two different coronary ostia heights (COHs, 8 and 10 mm). Results Validation of the model led to significant coronary obstruction (p < 0.001). Undersized TAViVI showed no significant reduction with respect to coronary flow (lCF: COH 8 mm, 0.90-0.87 mL/stroke; COH 10 mm, 0.89-0.82 mL/stroke and rCF: COH 8 mm, 0.64-0.60 mL/stroke; COH 10 mm, 0.62-0.58 mL/stroke). Mean transvalvular gradients (4-5 mm Hg, p < 0.001) increased significantly after TAViVI. Conclusions In our in vitro model, undersized TAViVI with the balloon-expandable Sapien XT into a modern generation SAVB (Trifecta) successfully avoided coronary flow obstruction.

Multivessel versus culprit lesion only percutaneous revascularization plus potential staged revascularization in patients with acute myocardial infarction complicated by cardiogenic shock: Design and rationale of CULPRIT-SHOCK trial.

BACKGROUND: In acute myocardial infarction complicated by cardiogenic shock (CS), up to 80% of patients present with multivessel coronary artery disease. Currently, the best revascularization strategy is unknown. Therefore, a prospective randomized adequately powered clinical trial is warranted. STUDY DESIGN: The CULPRIT-SHOCK study is a 706-patient controlled, international, multicenter, randomized, open-label trial. It is designed to compare culprit lesion only percutaneous coronary intervention (PCI) with possible staged non-culprit lesion revascularization versus immediate multivessel PCI in patients with CS complicating acute myocardial infarction. Patients will be randomized in a 1:1 fashion to one of the two treatment arms. The primary efficacy endpoint of CULPRIT-SHOCK is 30-day mortality and severe renal failure requiring renal replacement therapy. Secondary outcome measures such as hemodynamic, laboratory, and clinical parameters will serve as surrogate endpoints for prognosis. Furthermore, an intermediate- and long-term follow-up at 6 and 12 months will be performed. Safety endpoints include the assessment of bleeding and stroke. CONCLUSIONS: The CULPRIT-SHOCK trial will address the question of optimal revascularization strategy in patients with multivessel disease and acute myocardial infarction complicated by CS.

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).

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.

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.

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 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.

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.