LANDMARK comparison of early outcomes of newer-generation Myval transcatheter heart valve series with contemporary valves (Sapien and Evolut) in real-world individuals with severe symptomatic native aortic stenosis: a randomised non-inferiority trial.

BACKGROUND: Transcatheter aortic valve implantation is an established, guideline-endorsed treatment for severe aortic stenosis. Precise sizing of the balloon-expandable Myval transcatheter heart valve (THV) series with the aortic annulus is facilitated by increasing its diameter in 1·5 mm increments, compared with the usual 3 mm increments in valve size. The LANDMARK trial aimed to show non-inferiority of the Myval THV series compared with the contemporary THVs Sapien Series (Edwards Lifesciences, Irvine, CA, USA) or Evolut Series (Medtronic, Minneapolis, MN, USA). METHODS: In this prospective, multinational, randomised, open-label, non-inferiority trial across 31 hospitals in 16 countries (Germany, France, Sweden, the Netherlands, Italy, Spain, New Zealand, Portugal, Greece, Hungary, Poland, Slovakia, Slovenia, Croatia, Estonia, and Brazil), 768 participants with severe symptomatic native aortic stenosis were randomly assigned (1:1) to the Myval THV or a contemporary THV. Eligibility was primarily decided by the heart team in accordance with 2021 European Society of Cardiology guidelines. As per the criteria of the third Valve Academic Research Consortium, the primary endpoint at 30 days was a composite of all-cause mortality, all stroke, bleeding (types 3 and 4), acute kidney injury (stages 2-4), major vascular complications, moderate or severe prosthetic valve regurgitation, and conduction system disturbances resulting in a permanent pacemaker implantation. Non-inferiority of the study device was tested in the intention-to-treat population using a non-inferiority margin of 10·44% and assuming an event rate of 26·10%. This trial is registered with ClinicalTrials.gov, NCT04275726, and EudraCT, 2020-000137-40, and is closed to new participants. FINDINGS: Between Jan 6, 2021, and Dec 5, 2023, 768 participants with severe symptomatic native aortic stenosis were randomly assigned, 384 to the Myval THV and 384 to a contemporary THV. 369 (48%) participants had their sex recorded as female, and 399 (52%) as male. The mean age of participants was 80·0 years (SD 5·7) for those treated with the Myval THV and 80·4 years (5·4) for those treated with a contemporary THV. Median Society of Thoracic Surgeons scores were the same in both groups (Myval 2·6% [IQR 1·7-4·0] vs contemporary 2·6% [1·7-4·0]). The primary endpoint showed non-inferiority of the Myval (25%) compared with contemporary THV (27%), with a risk difference of -2·3% (one-sided upper 95% CI 3·8, pnon-inferiority<0·0001). No significant difference was seen in individual components of the primary composite endpoint. INTERPRETATION: In individuals with severe symptomatic native aortic stenosis, the Myval THV met its primary endpoint at 30 days. FUNDING: Meril Life Sciences.

Impact of standard modifiable cardiovascular risk factors on 2-year all-cause mortality: Insights from an international cohort of 23,489 patients with acute coronary syndrome.

BACKGROUND: Controversial findings have been reported in the literature regarding the impact of the absence of standard modifiable cardiovascular risk factors (SMuRFs) on long-term mortality risk in patients with acute coronary syndrome (ACS). While the prognostic additive value of SMuRFs has been well described, the prognostic role of prior cardiovascular disease (CVD) by sex is less well-known in patients with and without SMuRFs. METHODS: EPICOR and EPICOR Asia are prospective, observational registries conducted between 2010 and 2014, which enrolled ACS patients in 28 countries across Europe, Latin America, and Asia. Association between SMuRFs (diabetes, dyslipidaemia, hypertension, and smoking) and 2-year postdischarge mortality was evaluated using adjusted Cox models stratified by geographical region. RESULTS: Among 23,489 patients, the mean age was 60.9 ± 11.9 years, 24.3% were women, 4,582 (20.1%) presented without SMuRFs, and 16,055 (69.5%) without prior CVD. Patients with SMuRFs had a higher crude 2-year postdischarge mortality (HR 1.86; 95% CI, 1.56-2.22; P < .001), compared to those without SMuRFs. After adjustment for potential confounding, the association between SMuRFs and 2-year mortality risk was substantially attenuated (HR 1.17, 95% CI 0.98-1.41; P = .087), regardless of the type of ACS. The risk conferred by prior CVD was added to the underlying risk of SMuRFs to provide risk-specific phenotypes (eg, women with SMuRFs and with prior CVD were at higher risk of dying than women without SMuRFs and without CVD; HR 1.67, 95% CI 1.34-2.06). CONCLUSIONS: In this large-scale international ACS cohort the absence of SMuRFs was not associated with a lower adjusted 2-year postdischarge mortality risk. Patients with both SMuRFs and prior CVD had a higher mortality irrespective of their sex.

Incidence, predictors, and clinical impact of bleeding recurrence in patients with prior gastrointestinal bleeding undergoing LAAC.

BACKGROUND: Gastrointestinal bleeding (GIB) is associated with a high recurrence rate and a prior GIB episode is common in real-world left atrial appendage closure (LAAC) recipients. The present study sought to evaluate the clinical characteristics and outcomes of patients with prior GIB undergoing LAAC, and to determine the factors associated with and clinical impact of GIB recurrence. METHODS: Multicenter study including 277 consecutive patients who underwent percutaneous LAAC and had prior GIB. All-cause death, all bleeding, GIB recurrence, and clinical ischemic stroke were recorded. RESULTS: After a median follow-up of 17 (interquartile range: 6-37) months post-LAAC, the rates of death, bleeding, GIB recurrence, and ischemic stroke were 14.0 per 100 person-year (PY), 29.3 per 100 PY, 17.7 per 100 PY, and 1.1 per 100 PY, respectively. GIB recurrence occurred within 3 months post-LAAC in 55.8% of patients. A previous lower GIB (vs. upper or unclassified) (HR: 1.76; 95% CI: 1.09-2.82; p = .020) and eGFR < 45 mL/min (HR: 1.70; 95% CI:1.04-2.67; p = .033) determined an increased risk of GIB recurrence. By multivariable analysis, eGFR < 45 mL/min (HR: 2.72; 95% CI: 1.70-4.34; p < .001), GIB recurrence following LAAC (HR: 2.15; 95% CI: 1.33-3.46; p = .002), diabetes mellitus (HR: 1.77; 95% CI: 1.10-2.84; p = .018), and age (HR: 1.06; 95% CI: 1.03-1.10; p < .001) were associated with an increased mortality. CONCLUSIONS: Patients with prior GIB undergoing LAAC exhibited a relatively low rate of GIB recurrence, and prior lower GIB and moderate-to-severe chronic kidney disease determined an increased risk. GIB recurrence was associated with an increased mortality.

Short-course antibiotic regimen compared to conventional antibiotic treatment for gram-positive cocci infective endocarditis: randomized clinical trial (SATIE).

BACKGROUND: Most serious complications of infective endocarditis (IE) appear in the so-called "critical phase" of the disease, which represents the first days after diagnosis. The majority of patients overcoming the acute phase has a favorable outcome, yet they remain hospitalized for a long period of time mainly to complete antibiotic therapy. The major hypothesis of this trial is that in patients with clinically stable IE and adequate response to antibiotic treatment, without signs of persistent infection, periannular complications or metastatic foci, a shorter antibiotic time period would be as efficient and safe as the classic 4 to 6 weeks antibiotic regimen. METHODS: Multicenter, prospective, randomized, controlled open-label, phase IV clinical trial with a non-inferiority design to evaluate the efficacy of a short course (2 weeks) of parenteral antibiotic therapy compared with conventional antibiotic therapy (4-6 weeks). SAMPLE: patients with IE caused by gram-positive cocci, having received at least 10 days of conventional antibiotic treatment, and at least 7 days after surgery when indicated, without clinical, analytical, microbiological or echocardiographic signs of persistent infection. Estimated sample size: 298 patients. INTERVENTION: Control group: standard duration antibiotic therapy, (4 to 6 weeks) according to ESC guidelines recommendations. Experimental group: short-course antibiotic therapy for 2 weeks. The incidence of the primary composite endpoint of all-cause mortality, unplanned cardiac surgery, symptomatic embolisms and relapses within 6 months after the inclusion in the study will be prospectively registered and compared. CONCLUSIONS: SATIE will investigate whether a two weeks short-course of intravenous antibiotics in patients with IE caused by gram-positive cocci, without signs of persistent infection, is not inferior in safety and efficacy to conventional antibiotic treatment (4-6 weeks). TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04222257 (January 7, 2020). EudraCT 2019-003358-10.

Type of evidence supporting ACC/AHA and ESC clinical practice guidelines for acute coronary syndrome.

AIM: The aim of clinical practice guidelines for ST elevation myocardial infarction (STEMI) and non-ST elevation acute coronary syndrome (NSTE-ACS) is to assist healthcare professionals in clinical decision-making. We evaluated the type of studies supporting these guidelines and their recommendations. METHODS: All references and recommendations in the 2013 and 2014 ACC/AHA and 2017 and 2020 (ESC clinical guidelines for STEMI and NSTE-ACS were reviewed. References were classified into meta-analyses, randomised, non-randomised, and other types (e.g., position papers, reviews). Recommendations were classified according to class and their level of evidence (LOE). RESULTS: We retrieved 2128 non-duplicated references: 8.4% were meta-analyses, 26.2% randomised studies, 44.7% non-randomised studies, and 20.7% 'other' papers. Meta-analyses were based on randomised data in 78% of cases and used individual-patient data in 20.2%. Compared to non-randomised studies, randomised studies were more frequently multicentre (85.5% vs. 65.5%) and international (58.2% vs. 28.5%). The type of studies supporting recommendations varied as per the LOE of the recommendation. For LOE-A recommendations, the breakdown of supporting recommendations was: 18.5% meta-analyses, 56.6% randomised studies, 16.6% non-randomised studies and 8.3% 'other' papers; for LOE-B this breakdown was 9%, 39.8%, 38.2%, and 12.9%; and for LOE-C; 4.6%, 19.3%, 30.3%, and 45.9%. CONCLUSIONS: The references supporting the ACC/AHA and ESC guidelines on STEMI and NSTE-ACS consisted of non-randomised studies in ~ 45% of cases, with less than a third of the references consisting of meta-analyses and randomised studies. The type of studies supporting guideline recommendations varied widely by the LOE of the recommendation.

A systematic assessment of the characteristics of randomized controlled trials cited by acute coronary syndrome clinical practice guidelines.

AIMS: The aim of this study was to describe the methodological features of the randomized controlled trials (RCTs) cited in American and European clinical practice guidelines (CPGs) for ST elevation myocardial infarction (STEMI) and non-ST elevation acute coronary syndrome (NSTE-ACS). METHODS AND RESULTS: Out of 2128 non-duplicated references cited in the 2013 and 2014 American College of Cardiology/American Heart Association and 2017 and 2020 European Society of Cardiology CPGs for STEMI and NSTE-ACS, we extracted data for 407 RCTs (19.1% of total references). The majority were multicenter studies (81.8%), evaluated pharmacological interventions (63.1%), had a 2-arm (82.6%), and superiority (90.4%) design. Most RCTs (60.2%) had an active comparator, and 46.2% were funded by industry. The median observed sample size was 1001 patients (84.2% of RCTs achieved ≥80% of the intended sample size). Most RCTs had a single primary outcome (90.9%), which was a composite in just over half (51.9%). Among the RCTs testing for superiority, 44.0% reported a P-value of ≥0.05 for the primary outcome and 61.9% observed a risk reduction of >15%. The observed treatment effect was lower-than-expected in 67.6% of RCTs, with 34.4% having at least a 20% lower-than-expected treatment effect. The calculated post hoc statistical power was ≥80% for 33.9% of cited RCTs. CONCLUSIONS: This analysis demonstrates that RCTs cited by CPGs can still have significant methodological issues and limitations, highlighting that a better understanding of the methodological aspects of RCTs is crucial in order to formulate recommendations relevant to clinical practice.

The fragility index in randomized clinical trials supporting clinical practice guidelines for acute coronary syndrome: measuring robustness from a different perspective.

AIMS: In randomized clinical trials (RCTs) rejecting the null hypothesis, the fragility index (FI) yields the minimum number of participants who would need to have had a different outcome for the results of the trial to become non-significant. We evaluated the robustness of RCTs supporting American College of Cardiology/American Heart Association (ACC/AHA) and European Society of Cardiology (ESC) clinical practice guidelines (CPGs) for ST-elevation myocardial infarction (STEMI) and non-ST-elevation acute coronary syndrome (NSTE-ACS) using the FI. METHODS AND RESULTS: There were 407 RCTs among the 2128 studies cited in the 2013 and 2014 ACC/AHA and 2017 and 2020 ESC CPGs for STEMI and NSTE-ACS, respectively. The FI could be calculated in 132 RCTs (32.4%) meeting the needed criteria for its estimation (two-arm RCT, 1:1 allocation, binary outcome, P < 0.05). The median FI was 12 (interquartile range: 4-29). Hence, a change in the outcome status of 12 patients would be needed to reverse the statistical significance of the primary endpoint in 50% of the RCTs. The FI was ≤1% than their sample size in 55.7% RCTs, whereas in 47% of RCTs, the FI was lower than the number of patients lost to follow-up. Some study design features were associated with a higher FI (international, multicentre, private funding; all P < 0.05), whilst baseline patient characteristics were not substantially different by FI (e.g. age, female sex, white study participants; all P > 0.05), except for geographic enrolment (P = 0.042). CONCLUSION: The FI might be useful to evaluate the robustness of those RCTs with statistically significant findings for the primary endpoint that have an impact on key guideline recommendations.

Representativeness in randomised clinical trials supporting acute coronary syndrome guidelines.

AIMS: Clinical practice guidelines (CPGs) are published to guide the management of acute coronary syndrome (ACS). We aimed to critically appraise the representativeness and standard of care of randomised clinical trials (RCTs) supporting CPGs for ACS. METHODS AND RESULTS: American and European CPGs for ST- and non-ST-elevation ACS were screened to extract all references (n = 2128) and recommendations (n = 600). Among the 407 primary publications of RCTs (19.1%), there were 52.6 and 73.2% recruiting patients in North America and Europe, respectively, whereas other regions were largely under-represented (e.g. 25.3% RCTs recruited in Asia). There was 68.6% RCTs enrolling patient with ACS, whereas the remaining 31.4% did not enrol any patient with ACS. There was under-representation of some important subgroups, including elderly, female (29.9%), and non-white patients (<20%). The incidence and type of reperfusion reported in these RCTs were not reflective of current clinical practice (the percentage of patients who underwent percutaneous coronary intervention (PCI) among all RCTs was 42.7%; whereas for ST-Elevation Myocardial Infarction patients, the number of participants who underwent fibrinolysis was 3.3-fold higher than those who underwent primary PCI). All-cause mortality in these RCTs was 11.9% in RCTs with a follow-up ≤ 1 year. CONCLUSION: Randomised clinical trials supporting CPGs for ACS are not fully representative of the diversity of the ACS population and their current standard of care. While some of these issues with representativeness may be explained by how evidence has been accrued over time, efforts should be made by trialists to ensure that the evidence supporting CPGs is representative of the wider ACS population.

Very long-term efficacy and safety of paclitaxel-eluting balloon after a bare-metal stent for the treatment of ST-elevation myocardial infarction: 8-year results of a randomized clinical trial (PEBSI study).

Background: Drug-eluting stents (DES) are considered the therapy of choice in ST-segment elevation myocardial infarction (STEMI); however, a low persistent rate of revascularizations and stent thrombosis exist over the time. We have previously shown that a paclitaxel (PTX)-drug-coated balloon (DCB) after a bare-metal stent (BMS) implantation (DCB-combined strategy) yields superior angiographic and clinical results compared to BMS in the short term. However, the long-term safety and efficacy of this approach remain uncertain. Methods: An 8-year clinical follow-up was conducted on patients enrolled in the randomized PEBSI-1 trial (NCT01839890). The original trial included patients who suffered a STEMI, patients were randomly assigned to receive a DCB-combined strategy or BMS only and the primary endpoint was in-stent late luminal loss (LLL) at 9-month follow-up. After the completion of this study, death, myocardial re-infarction, ischemia-driven repeated revascularizations included target lesion revascularization (TLR) and target vessel revascularization (TVR), and stent thrombosis, were assessed by yearly contact by a clinical visit, telephone or by electronic records. These outcomes were adhered to ARC-2 criteria. Results: The rate of incomplete follow-up was very low, with only 3 out of 111 patients (2.7%) in the DCB-combined strategy group and 1 out of 112 patients (0.9%) in the BMS group. At 8 years there were a lower rate of TVR [3.7% vs. 14.3%; hazard ratio (HR): 0.243; 95% confidence interval (CI): 0.081-0.727; P=0.006], and a trend towards lower TLR (2.8% vs. 8.9%; HR: 0.300; 95% CI: 0.083-1.090; P=0.052) in the DCB-combined strategy group. No statistical difference between the DCB-combined strategy and BMS groups were found for all causes of death, deaths from cardiovascular disease, reinfarctions or stent thrombosis. Notably in the DCB-combined strategy group, no episode of stent thrombosis occurred after the first year. Similarly, there were no cardiovascular deaths, TVR and TLR in the DCB-combined strategy group after 5 years. In contrast, during the period from year 5 to 8, the BMS group experienced an additional cardiovascular death, as well as one case of TVR, one case of TLR, and one case of stent thrombosis. Conclusions: In STEMI patients, the DCB-combined strategy maintains its safety and clinical efficacy over time. Our rates of TVR, TLR, and very late stent thrombosis (VLST) at very long-term are the lowest ever found in a STEMI trial. Further studies are warranted to assess the potential superiority of this novel strategy as compared with new-generation DES to prevent very late events in these patients. Trial Registration: ClinicalTrials.gov; identifier: NCT01839890.

Ruptured sinus of Valsalva aneurysm: A reversible cause of suprasystemic pulmonary hypertension.

Management of patients with congenital heart defects and associated pulmonary arterial hypertension remains a major concern. With evolving targeted drug therapies and new iterations of transcatheter devices, treatment of appropriately selected patients with severe pulmonary hypertension, classically considered inoperable, has become feasible. We report the case of a patient with concomitant ruptured right sinus of Valsalva aneurysm and ventricular septal defect, with early reversal of suprasystemic pulmonary pressures following successful percutaneous closure of ruptured sinus of Valsalva.

Early Discontinuation of Antithrombotic Treatment Following Left Atrial Appendage Closure.

Although antithrombotic treatment is recommended after left atrial appendage closure (LAAC), some patients require discontinuation of antithrombotic treatment after LAAC without evidence on the safety of such a strategy. We sought to evaluate outcomes of patients who had early antithrombotic treatment discontinuation after LAAC. This is a multicenter study including 1,082 patients who underwent successful LAAC. Early discontinuation of antithrombotic treatment was defined as discontinuation of all antiplatelet/anticoagulant treatment within 6 months following the procedure. A propensity-matched analysis was used to compare outcomes of patients with and without early antithrombotic treatment discontinuation. A total of 148 patients (13.7%) had early antithrombotic treatment discontinuation. In the entire population, antithrombotic treatment discontinuation patients exhibited a lower CHA2DS2-VASc score (p <0.001) and a higher rate of previous gastrointestinal bleeding episodes (p = 0.01) compared with patients without discontinuation. After a median follow-up of 2.1 (1,1-3.1) years after antithrombotic treatment discontinuation, the rates of death, ischemic stroke, and major bleeding were 12.1, 0.6, and 3.3 per 100 patient-years. In 119 matched pairs with similar baseline characteristics, antithrombotic treatment discontinuation patients had a similar risk of death (hazard ratio [HR] 1.06, 95% confidence interval [CI] 0.65 to 1.71, p = 0.82), ischemic stroke (HR 0.39, 95% CI 0.04 to 3.79, p = 0.42) and major bleeding (HR 1.48, 95% CI 0.56 to 3.88, p = 0.43) compared with those without discontinuation. In conclusion, antithrombotic treatment was discontinued in 1 of 7 selected patients within 6 months after LAAC, and this was not associated with an increased risk of death or thromboembolic events after a median follow-up of 2 years. These data support the safety of shorter periods of antithrombotic therapy after LAAC in high bleeding risk patients based on clinician judgment. Further trials are warranted.

Incidence and Predictors of Early Death in Patients Undergoing Percutaneous Left Atrial Appendage Closure.

BACKGROUND: Left atrial appendage closure (LAAC) aims to prevent ischemic events in patients with atrial fibrillation. As a preventive procedure, early death after LAAC could render the procedure futile. OBJECTIVES: The authors sought to evaluate the incidence and factors associated with early death in LAAC recipients. METHODS: This was a multicenter study including consecutive patients undergoing LAAC in a 10-year period (2009-2019). Death was considered early when occurring in the first year after LAAC. RESULTS: A total of 807 patients (mean age 76 ± 8 years, mean CHA2DS2-VASc score 4.5 ± 1.5) were included. Early death occurred in 125 patients (15.5%). In the multivariable analysis, factors associated with early death after LAAC were older age HR: 1.03; 95% CI: 1.01-1.06 per year; P = 0.01), lower body mass index (HR: 0.92; 95% CI: 0.88-0.97 per 1 kg/m2 increase; P < 0.001), diabetes (HR: 1.71; 95% CI: 1.19-2.47; P = 0.002), prior heart failure (HR: 1.74; 95% CI: 1.20-2.53; P = 0.001), and lower estimated glomerular filtration rate (HR: 1.09; 95% CI: 1.05-1.13 per 5 mL/min/1.73 m2 decrease; P < 0.001). There was a stepwise increase in risk of early death within the first year of LAAC with the combination of different risk factors (up to 48.9% in the presence of >3 risk factors). CONCLUSIONS: In this multicenter international registry, close to 1 in 6 patients died within the first year of LAAC. Older age, low body mass index, impaired estimated glomerular filtration rate, prior diabetes, and prior heart failure are independently associated with an increased risk. The risk of early death appeared to be prohibitive (∼50%) in the presence of >3 of these risk factors.

Predictive Power for Thrombus Detection after Atrial Appendage Closure: Machine Learning vs. Classical Methods.

Device-related thrombus (DRT) after left atrial appendage (LAA) closure is infrequent but correlates with an increased risk of thromboembolism. Therefore, the search for DRT predictors is a topic of interest. In the literature, multivariable methods have been used achieving non-consistent results, and to the best of our knowledge, machine learning techniques have not been used yet for thrombus detection after LAA occlusion. Our aim is to compare both methodologies with respect to predictive power and the search for predictors of DRT. To this end, a multicenter study including 1150 patients who underwent LAA closure was analyzed. Two lines of experiments were performed: with and without resampling. Multivariate and machine learning methodologies were applied to both lines. Predictive power and the extracted predictors for all experiments were gathered. ROC curves of 0.5446 and 0.7974 were obtained for multivariate analysis and machine learning without resampling, respectively. However, the resampling experiment showed no significant difference between them (0.52 vs. 0.53 ROC AUC). A difference between the predictors selected was observed, with the multivariable methodology being more stable. These results question the validity of predictors reported in previous studies and demonstrate their disparity. Furthermore, none of the techniques analyzed is superior to the other for these data.

Management and outcomes of patients with left atrial appendage thrombus prior to percutaneous closure.

OBJECTIVE: Left atrial appendage (LAA) thrombus has heretofore been considered a contraindication to percutaneous LAA closure (LAAC). Data regarding its management are very limited. The aim of this study was to analyse the medical and invasive treatment of patients referred for LAAC in the presence of LAA thrombus. METHODS: This multicentre observational registry included 126 consecutive patients referred for LAAC with LAA thrombus on preprocedural imaging. Treatment strategies included intensification of antithrombotic therapy (IAT) or direct LAAC. The primary and secondary endpoints were a composite of bleeding, stroke and death at 18 months, and procedural success, respectively. RESULTS: IAT was the preferred strategy in 57.9% of patients, with total thrombus resolution observed in 60.3% and 75.3% after initial and subsequent IAT, respectively. Bleeding complications and stroke during IAT occurred in 9.6% and 2.9%, respectively, compared with 3.8% bleeding and no embolic events in the direct LAAC group before the procedure. Procedural success was 90.5% (96.2% vs 86.3% in direct LAAC and IAT group, respectively, p=0.072), without cases of in-hospital thromboembolic complications. The primary endpoint occurred in 29.3% and device-related thrombosis was found in 12.8%, without significant difference according to treatment strategy. Bleeding complications at 18 months occurred in 22.5% vs 10.5% in the IAT and direct LAAC group, respectively (p=0.102). CONCLUSION: In the presence of LAA thrombus, IAT was the initial management strategy in half of our cohort, with initial thrombus resolution in 60% of these, but with a relatively high bleeding rate (~10%). Direct LAAC was feasible, with high procedural success and absence of periprocedural embolic complications. However, a high rate of device-related thrombosis was detected during follow-up.

Assessment of the ESC quality indicators in patients with acute myocardial infarction: a systematic review.

AIMS: To help improving quality of care in patients with acute myocardial infarction (AMI), the European Society of Cardiology (ESC) set 20 quality indicators (QIs). There is a need to compile and summarize QI availability, feasibility, and global compliance in real-world registries. METHODS AND RESULTS: A systematic review of PubMed and Web of Science was conducted including all original articles reporting the use of the ESC QIs in AMI patients. Methods and reporting follow the guidelines of the PRISMA Statement and the protocol was registered in PROSPERO (CRD42020190541). Among the 220 screened citations, 9 studies met the inclusion criteria after full-text review. Among these 9 studies, there were 11 different cohorts. Patients were recruited from three different continents (31 countries). The number of QIs assessed ranged from 6 to 20, with 5 studies (56%) reporting data for at least 75% of the 20 QIs. There were room for improvement in terms of data availability (i.e. domain 6 measuring patient's satisfaction), feasibility (i.e. difficulties to find all data for composite QIs in domain 7), and attainment (i.e. high levels of compliance with the percentage of reperfused ST-segment elevation myocardial infarction patients, but low levels for a timely reperfusion). CONCLUSIONS: Our systematic review has shown that it is possible to measure most QIs in existing registries, and that there is room for improvement in terms of data availability, feasibility, and levels of attainment to QIs. Our findings may influence the design of future registries to capture this information and help in QIs definition updates.

Familial Dilated Cardiomyopathy and Sudden Cardiac Arrest: New Association with a SCN5A Mutation.

Dilated cardiomyopathy (DCM) has significant morbidity and mortality. Familial transmission is reported in 20-35% of cases, highlighting the role of genetics in this disorder. We present an interesting family in which the index case is a 64-year-old woman who survived a sudden cardiac arrest. She presented left ventricular dilatation and dysfunction, which indicated the presence of DCM, as well as a history of DCM and sudden arrest in her family (mother and sister). Genetic testing identified a heterozygous mutation c.74A > G missense change that causes an amino acid, p.Glu25Gly, change in the N-terminal domain of the SCN5A protein. After performing an exhaustive family medical history, we found that this previously not described mutation segregated within the family. All relatives with the DCM phenotype were carriers, whereas none of the noncarriers showed signs of heart disease, so this mutation is the most likely cause of the disease. This is the first time that a variant in the N-terminal domain of SCN5A has been associated with DCM.

Early coronary healing in ST segment elevation myocardial infarction: sirolimus-eluting stents vs. drug-coated balloons after bare-metal stents. The PEBSI-2 optical coherence tomography randomized study.

OBJECTIVES: Drug-coated balloons (DCBs) have theoretical advantages over drug-eluting stents (DESs) to facilitate stent healing. We studied whether, in patients undergoing primary coronary interventions (pPCIs), a strategy of DCB after bare-metal stent improves early healing as determined by optical coherence tomography (OCT) compared with new-generation DES. METHODS: pPCI patients were randomized (1:1) to treatment with new-generation sirolimus-eluting stents (DES group) or DCB-strategy. Vessel healing was assessed by OCT at 90 days. RESULTS: Fifty-three patients were randomized (26 DES vs. 27 DCB). At 90 days, both strategies showed a low rate of uncovered struts (3.2 vs. 3.2%, P = 0.64) and a very high and similar rate of covered and apposed struts (96.6 vs. 96.1%, respectively; P = 0.58). However, DCB group had a significantly lower rate of major coronary evaginations (68 vs. 37%, P = 0.026), and more frequently developed a thin homogeneous neointimal layer (20 vs. 70.4%, P = 0.001) suggesting distinct superior healing at 3 months compared to DES. CONCLUSIONS: In pPCI both, sirolimus-DES and DCB-strategy, provide excellent strut coverage at 3 months. However, DCB ensures more advanced and optimal stent healing compared to sirolimus-DES. Further research is needed to determine whether, in patients undergoing pPCI, DCB offers superior long-term clinical and angiographic outcomes than new-generation DES (NCT03610347).

Effect of Glomerular Filtration Rates on Outcomes Following Percutaneous Left Atrial Appendage Closure.

Scarce data support the prescription of oral anticoagulation in patients with concomitant advanced chronic kidney disease (CKD) and atrial fibrillation, and left atrial appendage closure (LAAC) may provide a favorable risk-benefit ratio in this population. However, outcomes of LAAC in CKD patients are unknown. We aimed to investigate the impact of moderate-to-severe CKD on clinical outcomes following percutaneous LAAC. This was a multicenter study including 1094 patients who underwent LAAC. Moderate-to-severe CKD was defined as an eGFR<45 mL/min. Death, ischemic stroke, severe bleeding (≥BARC 3a) and serious adverse event (SAE; composite of death, stroke or severe bleeding) were recorded. A total of 300 patients (27.4%) had moderate-to-severe CKD. There were no differences between groups in periprocedural complications or device related thrombosis. At a median follow-up of 2 (1 to 3) years, patients with moderate-to-severe CKD did not present an increased risk of ischemic stroke (hazard ratio [HR]: 0.65; 95% confidence interval [CI]: 0.22 to 1.92; p = 0.435) but were at a higher risk of death (HR: 2.84; 95% CI: 2.22 to 3.64; p <0.001), severe bleeding (HR: 1.96; 95% CI: 1.36 to 2.81; p <0.001) and SAE (HR: 2.23; 95% CI: 1.80 to 2.77; p <0.001). By multivariable analysis, an eGFR<45 ml/min (HR: 1.92; 95% CI: 1.34 to 2.76; p <0.001) and previous bleeding (HR: 2.30; 95% CI: 1.27 to 4.17; p = 0.006) were associated with an increased risk of severe bleeding. In conclusion, patients with moderate-to-severe CKD who underwent LAAC had very high thrombotic and bleeding risks. Although the rates of device related thrombosis or ischemic stroke after-LAAC were not influenced by kidney dysfunction, patients with moderate-to-severe CKD remained at higher risk of severe bleeding events.

Short-term direct oral anticoagulation or dual antiplatelet therapy following left atrial appendage closure in patients with relative contraindications to chronic anticoagulation therapy.

BACKGROUND: Biological data suggest that short-term anticoagulation would be more effective than dual antiplatelet therapy (DAPT) to reduce the thrombotic risk following left atrial appendage closure (LAAC). This study sought to assess the safety and efficacy of direct oral anticoagulation (DOAC) versus DAPT immediately post-LAAC. METHODS: Multicenter study including 592 consecutive patients with relative contraindication to chronic anticoagulation who underwent LAAC and received either DAPT or DOAC for 1-3 months. Each patient receiving DOAC was matched with 2 patients on DAPT based on propensity-score (propensity-matched population of 285 patients). Outcomes recorded were death, stroke, non-procedural related severe bleeding, serious adverse event (SAE: composite of death, stroke, bleeding) and early (within 3 months post-LAAC) device-related thrombosis (DRT). RESULTS: Early outcomes (within 3-month post-LAAC) did not significantly differ between groups, but a numerically higher rate of early death (3.7% vs. 1.1%), non-procedural related severe bleeding (7.4% vs. 3.2%), and SAE (11.1% vs. 5.3%) were observed in patients receiving DAPT. After a median follow-up of 22 (8-38) months, similar outcomes were observed in DAPT and DOAC groups regarding death (HR: 1.18; 95% CI: 0.58-2.37; p = 0.652), stroke (HR: 1.01; 95% CI: 0.22-5.45; p = 0.908), non-procedural related severe bleeding (HR: 1.68; 95% CI: 0.69-4.12; p = 0.257), and SAE (HR: 1.28; 95% CI: 0.73-2.24; p = 0.383). DRT was identified in 4 patients (2.6%) receiving DAPT versus 0 patient receiving DOAC (p = 0.162). CONCLUSIONS: Short-term DOAC following LAAC in patients with contraindications to chronic anticoagulation was safe and tended to associate with a lower rate of SAE and DRT compared to DAPT.