Echocardiographic and clinical features of patients developing prosthesis-patient mismatch after TAVR: insights from the Recovery TAVR registry.

BACKGROUND: The impact of prosthesis-patient mismatch (PPM) on major endpoints after transcatheter aortic valve replacement (TAVR) is controversial and the effects on progression of heart damage are poorly investigated. Therefore, our study aims to evaluate the prevalence and predictors of PPM in a "real world" cohort of patients at intermediate and low surgical risk, its impact on mortality and the clinical-echocardiographic progression of heart damage. METHODS: 963 patients who underwent TAVR procedure between 2017 and 2021, from the RECOVERY-TAVR international multicenter observational registry, were included in this analysis. Multiparametric echocardiographic data of these patients were analyzed at 1-year follow-up (FU). Clinical and echocardiographic features were stratified by presence of PPM and PPM severity, as per the most current international recommendations, using VARC-3 criteria. RESULTS: 18% of patients developed post-TAVR. PPM, and 7.7% of the whole cohort had severe PPM. At baseline, 50.3% of patients with PPM were male (vs 46.2% in the cohort without PPM, p=0.33), aged 82 (IQR 79-85y) years vs 82 (IQR 78-86 p=0.46), and 55.6% had Balloon-Expandable valves implanted (vs 46.8% of patients without PPM, p=0.04); they had smaller left ventricular outflow tract (LVOT) diameter (20 mm, IQR 19-21 vs 20 mm, IQR 20-22, p=0.02), reduced SVi (34.2 vs 38 ml/m2, p<0.01) and transaortic flow rate (190.6 vs 211 ml/s, p<0.01). At pre-discharge FU patients with PPM had more paravalvular aortic regurgitation (moderate-severe AR 15.8% vs 9.2%, p<0.01). At 1-year FU, maladaptive alterations of left ventricular parameters were found in patients with PPM, with a significant increase in end-systolic diameter (33 mm vs 28 mm, p=0.03) and a significant increase in left ventricle end systolic indexed volume in those with moderate and severe PPM (52 IQR 42-64 and 52, IQR 41-64 vs.44 IQR 35-59 in those without, p=0.02)). No evidence of a significant impact of PPM on overall (p=0.71) and CV (p=0.70) mortality was observed. Patients with moderate/severe PPM had worse NYHA functional class at 1 year (NYHA III-IV 13% vs 7.8%, p=0.03). Prosthesis size≤23 mm (OR 11.6, 1.68-80.1) was an independent predictor of PPM, while SVi (OR 0.87, 0.83-0.91, p<0.001) and LVOT diameter (OR 0.79, 0.65-0.95, p=0.01) had protective effect. CONCLUSIONS: PPM was observed in 18% of patients undergoing TAVR. Echocardiographic evaluations demonstrated a PPM-related pattern of early ventricular maladaptive alterations, possibly precursor to a reduction in cardiac function, associated with a significant deterioration in NYHA class at 1 year. These findings emphasize the importance of prevention of PPM of any grade in patients undergoing TAVR procedure, especially in populations at risk.

Percutaneous coronary intervention of unprotected left main and bifurcation in octogenarians: Subanalysis from RAIN (veRy thin stents for patients with left mAIn or bifurcatioN in real life).

OBJECTIVE: Outcomes of complex percutaneous coronary interventions (PCIs) in older patients are still debated. The aim of the study was to evaluate clinical outcomes of Octogenarian patients treated with ultrathinstents on left main or on coronary bifurcations, compared with younger patients. METHODS: All consecutive patients presenting a critical lesion of an unprotected left main (ULM) or a bifurcation and treated with very thin stents were included in the RAIN (veRy thin stents for patients with left mAIn or bifurcatioN in real life) registry and divided into octogenarians group (OG, 551 patients) and nonoctogenarians (NOGs, 2,453 patients). Major adverse cardiovascular event (MACE), a composite end point of all-cause death, nonfatal myocardial infarction (MI), target lesion revascularization (TLR), and stent thrombosis (ST), was the primary endpoint, while MACE components, cardiovascular (CV) death, and target vessel revascularization (TVR) were the secondary ones. RESULTS: Indication for PCI was acute coronary syndrome in 64.7% of the OG versus 53.1% of the NOG. Severe calcifications and a diffuse disease were significantly more in OG. After a follow-up of 15.2 ± 10.3 months, MACEs were higher in the OG than in the NOG patients (OG 19.1% vs. NOG 11.2%, p < .001), along with MI (OG 6% vs. NOG 3.4%, p = .002) and all-cause death (OG 14% vs. NOG 4.3%, p < .001). In contrast, no significant difference was detected in CV-death (OG 5.1% vs. NOG 4%, p = .871), TVR/TLR, or ST. At multivariate analysis, age was not an independent predictor of MACE (OR 1.02 CI 95% 0.76-1.38), while it was for all-cause death, along with diabetes, GFR < 60 ml/min, and ULM disease. DISCUSSION: Midterm outcomes of complex PCI in OG are similar to those of younger patients. However, due to the higher non-CV death rate, accurate patient selection is mandatory.

Fractional flow reserve guided versus angiographic guided surgical revascularization: A meta-analysis.

BACKGROUND: Clinical benefits of FFR (Fraction Flow Reserve) driven CABG (Coronary Artery Bypass Graft) remain to be established. METHODS: All randomized controlled trials (RCTs) and observational studies with multivariable adjustement were included. MACE (Major Adverse Cardiac Events) was the primary end point, while its single components (death, myocardial infarction, and total vessel revascularization [TVR]) along with number of anastomoses, on pump procedures and graft occlusion at angiographic follow-up were the secondary ones. Each analysis was stratified for RCTs versus observational studies. RESULTS: Four studies (two RCTs and two observational) were included, enrolling 983 patients, 542 angio-guided and 441 FFR-guided. Mean age was 68.45 years, 79% male, with a mean EuroSCORE I of 2.7. Coronary lesions were located in 37% of patients in the left anterior descending artery, 32% in the circumflex artery, and 26% in the right coronary artery. After a mean follow-up of 40 months, risk of MACE did not differ (OR 0.86 [0.63-1.18]) as that of all cause death (OR 0.86 [0.59-1.25]), MI (OR 0.57 [0.30-1.11]) and TVR (OR 1.10 [0.65-1.85]). FFR-driven CABG reduced on-pump procedures (OR 0.58 [0.35-0.93]) and number of anastomoses (-0.40 [-0.80: -0.01]) while incidence of graft occlusion at follow-up did not differ (OR 0.59 [0.30-1.15], all CI 95%). CONCLUSION: Fraction flow reserve driven CABG reduced the number of anastomoses and of on-pump procedures without increasing risk of MACE and without reducing graft occlusion at angiographic follow-up. ID CRD42020211945.

Accuracy of the PARIS score and PCI complexity to predict ischemic events in patients treated with very thin stents in unprotected left main or coronary bifurcations.

BACKGROUND: The PARIS risk score (PARIS-rs) and percutaneous coronary intervention complexity (PCI-c) predict clinical and procedural residual ischemic risk following PCI. Their accuracy in patients undergoing unprotected left main (ULM) or bifurcation PCI has not been assessed. METHODS: The predictive performances of the PARIS-rs (categorized as low, intermediate, and high) and PCI-c (according to guideline-endorsed criteria) were evaluated in 3,002 patients undergoing ULM/bifurcation PCI with very thin strut stents. RESULTS: After 16 (12-22) months, increasing PARIS-rs (8.8% vs. 14.1% vs. 27.4%, p < .001) and PCI-c (15.2% vs. 11%, p = .025) were associated with higher rates of major adverse cardiac events ([MACE], a composite of death, myocardial infarction [MI], and target vessel revascularization), driven by MI/death for PARIS-rs and target lesion revascularization/stent thrombosis for PCI-c (area under the curves for MACE: PARIS-rs 0.60 vs. PCI-c 0.52, p-for-difference < .001). PCI-c accuracy for MACE was higher in low-clinical-risk patients; while PARIS-rs was more accurate in low-procedural-risk patients. ≥12-month dual antiplatelet therapy (DAPT) was associated with a lower MACE rate in high PARIS-rs patients, (adjusted-hazard ratio 0.42 [95% CI: 0.22-0.83], p = .012), with no benefit in low to intermediate PARIS-rs patients. No incremental benefit with longer DAPT was observed in complex PCI. CONCLUSIONS: In the setting of ULM/bifurcation PCI, the residual ischemic risk is better predicted by a clinical risk estimator than by PCI complexity, which rather appears to reflect stent/procedure-related events. Careful procedural risk estimation is warranted in patients at low clinical risk, where PCI complexity may substantially contribute to the overall residual ischemic risk.

Anticoagulant and anti-thrombotic therapy in acute type B aortic dissection: when real-life scenarios face the shadows of the evidence-based medicine.

BACKGROUND: Evidence-based recommendations about anticoagulation in acute type B aortic dissection (TBAD) are completely missing, but there is a diffuse conviction that it could prevent the healing process of the dissected aorta's false lumen. However, several clinical conditions may lead to the necessity to start anticoagulant therapy among patients with acute type B aortic dissection, ranging from atrial fibrillation to more complicated clinical scenarios and the correct management in this kind of patients is still an open issue. CASE PRESENTATION: We are presenting a 51-years-old man with multi-infarct encephalopathy referred to us for an acute TBAD and a first diagnosis of ischemic cardiomyopathy complicated by left ventricular (LV) thrombus formation. Coronary angiography revealed a critical stenosis of left anterior descending artery (LAD) treated with drug-eluting stent deployment. The patient was addressed to triple antithrombotic therapy with acetylsalicylic acid, clopidogrel and warfarin with target INR 2.0-2.5. After 6 months, computed tomography angiography revealed the stability of the dissection flap. Cardiac magnetic resonance imaging, however, confirmed the persistence of a small thrombotic formation in LV apex, thus double antithrombotic therapy with warfarin and clopidogrel was instituted. The patient remained asymptomatic during the follow-up period but was advised to suspend his job and physical activities. CONCLUSION: Current guidelines do not discuss anticoagulant therapy in the setting of TBAD and large randomized trials are lacking. Despite it is generally considered unsafe to administer anticoagulants in patients with TBAD, we present a case in which triple antithrombotic therapy was well tolerated and did not lead to progression of the intimal flap after 6 months.

De-escalation of dual antiplatelet therapy for patients with acute coronary syndrome after percutaneous coronary intervention: a systematic review and network meta-analysis.

OBJECTIVES: To compare dual antiplatelet therapy (DAPT) de-escalation with five alternative DAPT strategies in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). DESIGN: We conducted a systematic review and network meta-analysis (NMA). Parallel-arm randomised controlled trials (RCTs) comparing DAPT strategies were included and arms of interest were compared via NMA. Partial ranking of each identified arm and for each investigated endpoint was also performed. SETTING AND PARTICIPANTS: Adult patients with ACS (≥18 years) undergoing PCI with indications for DAPT. SEARCH METHODS: A comprehensive search covered several databases (PubMed, Embase, Cochrane Central, MEDLINE, Conference Proceeding Citation Index-Science) from inception to 15 October 2023. Medical subject headings and keywords related to ACS, PCI and DAPT interventions were used. Reference lists of included studies were screened. Clinical trials registers were searched for ongoing or unpublished trials. INTERVENTIONS: Six strategies were assessed: T1 arm: acetylsalicylic acid (ASA) and prasugrel for 12 months; T2 arm: ASA and low-dose prasugrel for 12 months; T3 arm: ASA and ticagrelor for 12 months; T4 arm: DAPT de-escalation (ASA+P2Y12 inhibitor for 1-3 months, then single antiplatelet therapy with potent P2Y12 inhibitor or DAPT with clopidogrel); T5 arm: ASA and clopidogrel for 12 months; T6 arm: ASA and clopidogrel for 3-6 months. MAIN OUTCOME MEASURES: Primary outcome: Cardiovascular mortality. SECONDARY OUTCOMES: bleeding events (all, major, minor), stent thrombosis (ST), stroke, myocardial infarction (MI), all-cause mortality, major adverse cardiovascular events (MACE). RESULTS: 23 RCTs (75 064 patients with ACS) were included. No differences in cardiovascular mortality, all-cause death, recurrent MI or MACE were found when the six strategies were compared, although with different levels of certainty of evidence. ASA and clopidogrel for 12 or 3-6 months may result in a large increase of ST risk versus ASA plus full-dose prasugrel (OR 2.00, 95% CI 1.14 to 3.12, and OR 3.42, 95% CI 1.33 to 7.26, respectively; low certainty evidence for both comparisons). DAPT de-escalation probably results in a reduced risk of all bleedings compared with ASA plus full-dose 12-month prasugrel (OR 0.49, 95% CI 0.26 to 0.81, moderate-certainty evidence) and ASA plus 12-month ticagrelor (OR 0.52, 95% CI 0.33 to 0.75), while it may not increase the risk of ST. ASA plus 12-month clopidogrel may reduce all bleedings versus ASA plus full-dose 12-month prasugrel (OR 0.66, 95% CI 0.42 to 0.94, low certainty) and ASA plus 12-month ticagrelor (OR 0.70, 95% CI 0.52 to 0.89). CONCLUSIONS: DAPT de-escalation and ASA-clopidogrel regimens may reduce bleeding events compared with 12 months ASA and potent P2Y12 inhibitors. 3-6 months or 12-month aspirin-clopidogrel may increase ST risk compared with 12-month aspirin plus potent P2Y12 inhibitors, while DAPT de-escalation probably does not.

Duration and kind of dual antiplatelet therapy for acute coronary syndrome patients: a network meta-analysis.

INTRODUCTION: For acute coronary syndrome (ACS) patients treated with percutaneous coronary intervention (PCI), the choice of the duration and kind of dual antiplatelet therapy (DAPT) offering the most accurate balance between ischemic and bleeding risk remains unknown. EVIDENCE ACQUISITION: A network meta-analysis was performed including all Randomized Controlled Trials (RCTs) comparing different DAPT regimens and duration in ACS patients undergoing PCI. Trial-defined MACE and major bleedings were the primary endpoints. Stroke, stent thrombosis (ST), all-cause and cardiovascular death, myocardial infarction (MI) represented secondary endpoints. EVIDENCE SYNTHESIS: 13 RCTs encompassing 46145 patients were included. Mean age was 62 (61-64) years old, 42% being admitted with STEMI, 33% with NSTEMI and 25% with UA. The competitive arms were: clopidogrel and aspirin for 12 months (6 arms/18183 patients), clopidogrel and aspirin for 6 months (4/3329), clopidogrel and aspirin >12 months (3/2238), ticagrelor and aspirin for 12 months (6/12942) and prasugrel and aspirin for 12 months (3/9453). Trial-defined MACE and major bleedings, stroke and death were similar among the different arms. DAPT with prasugrel and aspirin for 12 months reduced MI compared to aspirin and clopidogrel for 12 months (OR 0.71, 95% CI: 0.54.0.94) and reduced the risk of ST compared to ticagrelor (OR 0.66, 95% CI: 0.49-0.90). Both prasugrel and ticagrelor reduced ST as compared to clopidogrel and aspirin for 12 months. CONCLUSIONS: Different DAPT strategies yield similar risk of MACE, major bleeding, death and stroke in ACS patients. Prasugrel and aspirin for 12 months proved to be the most effective strategy regarding ST and MI.

Feasibility and reliability of comprehensive three-dimensional transoesophageal echocardiography screening process for transcatheter mitral valve replacement.

AIMS: The procedural planning of transcatheter mitral valve replacement (TMVR) requires a specific imaging assessment to establish patient eligibility. Computed tomography (CT) is considered the reference method. In this setting, data regarding the role of transoesophageal echocardiography (TOE) are lacking. We evaluated the feasibility and reliability of a comprehensive 3D-TOE screening in TMVR candidates. METHODS AND RESULTS: We performed a retrospective observational study including 72 consecutive patients who underwent a pre-procedural CT and 3D-TOE for TMVR evaluation. The measurements of mitral annulus (MA), length of anterior mitral leaflet (AML), native left ventricular outflow tract (LVOT), and predicted neo-LVOT acquired with CT and 3D-TOE were compared using a novel semi-automated software for post processing analysis (3 mensio Structural Heart 10.1-3mSH, Pie Medical Imaging, Bilthoven, Netherlands). The final suitability decision was given by the valve manufacturer based on CT measurements and clinical conditions. Among 72 patients screened, all patients had adequate image quality for 3D-TOE analysis. 3D-TOE and CT measurements for AML length (r = 0.97), MA area (r = 0.90), perimeter (r = 0.68), anteroposterior (r = 0.88), and posteromedial-anterolateral (r = 0.74) diameters were found highly correlated, as well as for native LVOT (r = 0.86) and predicted neo-LVOT areas (r = 0.96) (all P-values <0.0001). An almost perfect agreement between CT and 3DTOE was found in assessing the eligibility for TMVR implantation (Cohen kappa 0.83, P < 0.001). CONCLUSION: 3D-TOE appraisements showed good correlations with CT measurements and high accuracy to predict TMVR screening success.

Efficacy and safety of left atrial appendage closure compared with oral anticoagulation in atrial fibrillation: a meta-analysis of randomized controlled trials and propensity-matched studies.

Backgrounds: Two recent randomized controlled trials (RCTs), the PROTECT-AF and the PREVAIL, showed that in atrial fibrillation (AF) patients, left atrial appendage closure (LAAC) is comparable to oral anticoagulants (OAC) in the prevention of stroke and could also possibly reduce mortality. Nevertheless, this net clinical benefit was not confirmed in the most recent RCT comparing LAAC vs. OAC, the PRAGUE-17 trial. Aim: aim of the present study was to evaluate the efficacy and safety of LAAC compared with OAC among available high-quality studies. Methods: A systematic search of electronic databases (Medline, Scopus, Embase and the Cochrane Library) was performed to identify eligible RCTs and observational studies with propensity score matching (PSM) analysis. PRISMA guidelines were used for abstracting data and assessing data quality and validity. Outcomes of interest were the occurrence of cardiovascular death (CVD), all-cause death, all-type stroke, and major bleedings. Results: A total of 3 RCTs and 7 PMS studies involving 25,700 patients were identified. 12,961 patients received LAAC while 12,739 received OAC therapy. After a median follow-up of 2.6 years (IQR 2-4.4), patients who received LAAC had lower risk of CVD (RR = 0.62; 95%CI, 0.51-0.74, I2 = 0%), all-cause death (RR = 0.67; 95% CI, 0.57-0.78, I2 68%) and major bleedings (RR = 0.68; 95%CI, 0.48-0.95 I2 = 87%) compared with patients on OAC. No difference was found between the two groups regarding strokes incidence (RR = 0.94; 95% CI, 0.77-1.15, I2 = 0%). Conclusions: According to this meta-analysis, LAAC has comparable efficacy in the prevention of stroke compared with OAC and a reduced risk of major bleedings, all-cause death and CVD that may be even larger with longer follow-up. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=269768, identifier CRD42021269768.

Percutaneous coronary intervention versus coronary artery surgery for left main disease according to lesion site: A meta-analysis.

BACKGROUND: Comparative data after percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) for unprotected left main coronary artery (ULMCA) disease according to lesion site (ostial/shaft vs distal) are scant. The aim of this meta-analysis was to investigate outcomes after PCI or CABG for ULMCA disease according to lesion site. METHODS: Randomized controlled trials (RCTs) and adjusted observational studies that compared PCI versus CABG in patients with ULMCA disease and reported outcomes according to lesion site were systematically identified. Major adverse cardiovascular events (MACE; a composite of all-cause death, myocardial infarction, stroke, and repeat revascularization) and all-cause death were the co-primary end points. Individual components of MACE were secondary end points. Sensitivity analysis including RCTs only were performed for each outcome. RESULTS: Nine studies (3 RCTs, 6 adjusted observational), encompassing 6296 patients (2274 and 4022 treated for ostial/shaft or distal ULMCA, respectively) were included. At the 5-year follow-up, there were no significant differences between CABG and PCI for MACE, death, or any other secondary outcome for ostial/shaft ULMCA lesions (MACE: hazard ratio [HR], 1.0 [95% confidence interval (CI), 0.79-1.27]; death: HR, 1.10 [95% CI, 0.84-1.46]). For distal ULMCA, PCI was associated with an increased risk of MACE (HR, 1.32; 95% CI, 1.10-1.58), death (HR, 1.56; 95% CI, 1.19-2.04), and revascularization (HR, 2.07; 95% CI, 1.5-2.84). The benefit of CABG for MACE and revascularization was confirmed in the analysis limited to RCTs, whereas the benefit for mortality was not. CONCLUSIONS: Among patients with distal ULMCA disease, CABG is associated with lower incidence of MACE and revascularization compared with PCI, whereas no differences in outcomes were observed for ostial/shaft ULMCA disease.

Echocardiographic Parameters to Predict Malignant Events in Arrhythmic Mitral Valve Prolapse Population.

Bileaflet Mitral Valve Prolapse (bMVP) has been linked to major arrhythmic events and sudden cardiac death (SCD). Consistent predictors in this field are still lacking. Echocardiography is the best tool for the analysis of the prolapse and its impact on the ventricular mechanics. The aim of this study was to find new echocardiographic predictors of malignant events within an arrhythmic MVP population. We evaluated 22 patients with arrhythmic bMVP with a transthoracic echocardiogram focused on mitral valve anatomy and ventricular contraction. Six of them had major arrhythmic events that required ICD implantation (ICD-MVP group), while sixteen presented with a high arrhythmic burden without major events (A-MVP group). The best predictors of malignant events were the Anterior Mitral Leaflet (AML) greater length and greater Mechanical Dispersion (MD) of basal and mid-ventricular segments, while other significant predictors were the larger mitral valve annulus (MVA) indexed area, lower MVA anteroposterior diameter/AML length ratio, higher inferolateral basal segment S3 velocity.

Three-Dimensional Finger Test: A New Echocardiographic Method to Locate the Best Access Site During NeoChord Procedure.

OBJECTIVE: Transventricular beating-heart mitral valve repair (TBMVR) with artificial chordae implantation is a technique to treat mitral valve prolapse. Two-dimensional (2D) echocardiography completed with simultaneous biplane view during surgeon finger pushing on the left ventricular (LV) wall (finger test [FT]) is currently used to localize the desired LV access, on the inferior-lateral wall, between the papillary muscles (PMs). We aimed to compare a new three-dimensional (3D) method with conventional FT in terms of safety and better localization of LV access. METHODS: During TBMVR, conventional FT was completed using 3D transesophageal echocardiography by placing the sample box in the bicommissural view of the LV, including the PMs and the apex. The 3D volume was subsequently edited to visualize the LV from above (surgical view) to localize the bulge of the operator's finger pushing on the LV. We asked the first operator, the second operator, and the cardiac surgery fellow, separately, to evaluate the location of their finger pushing, both with the 2D method and the 3D method, to estimate the interoperator concordance. RESULTS: From 2019 to 2021, 42 TBMVRs were performed without complications related to access using FT completed with the 3D method. Regarding the choice of the right and safe entry site, the operator's agreement was higher using 3D rendering compared with conventional FT (mean agreement 0.59 ± 0.29 for 2D vs 0.83 ± 0.20 for 3D), while full operator agreement was 10 of 42 for 2D and 23 of 42 for 3D (P = 0.004). CONCLUSIONS: Three-dimensional FT is easy to perform and facilitates surgeons choosing the best access for TBMVR in term of anatomical localization and safety.

Two-Year clinical outcomes after coronary bifurcation stenting in older patients from Korea and Italy.

Background: Older patients who treated by percutaneous coronary intervention (PCI) are at a higher risk of adverse cardiac outcomes. We sought to investigate the clinical impact of bifurcation PCI in older patients from Korea and Italy. Methods: We selected 5,537 patients who underwent bifurcation PCI from the BIFURCAT (comBined Insights from the Unified RAIN and COBIS bifurcAtion regisTries) database. The primary outcome was a composite of target vessel myocardial infarction, clinically driven target lesion revascularization, and stent thrombosis at two years. Results: In patients aged ≥75 years, the mean age was 80.1 ± 4.0 years, 65.2% were men, and 33.7% had diabetes. Older patients more frequently presented with chronic kidney disease (CKD), severe coronary calcification, and left main coronary artery disease (LMCA). During a median follow-up of 2.1 years, older patients showed similar adverse clinical outcomes compared to younger patients (the primary outcome, 5.7% vs. 4.5%; p = 0.21). Advanced age was not an independent predictor of the primary outcome (p = 0.93) in overall patients. Both CKD and LMCA were independent predictors regardless of age group. Conclusions: Older patients (≥75 years) showed similar clinical outcomes to those of younger patients after bifurcation PCI. Advanced age alone should not deter physicians from performing complex PCIs for bifurcation disease.

Stroke volume index and transvalvular flow rate trajectories in severe aortic stenosis treated with TAVR.

AIMS: The prognostic impact of flow trajectories according to stroke volume index (SVi) and transvalvular flow rate (FR) in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) remains poorly assessed. We evaluated and compared SVi and FR prior and after TAVR for severe AS. METHODS AND RESULTS: Patients were categorized according to SVi (<35 mL/m2) and FR (<200 mL/s). The association of pre- and post-TAVR SVi and FR with all-cause mortality up to 3 years was assessed with multivariable Cox regression models. Among 980 patients with pre-TAVR flow assessment, SVi was reduced in 41.3% and FR in 48.1%. Baseline flow status was not an independent mortality predictor [SVi: hazard ratio (HR) 1.22, 95% confidence interval (CI) 0.85-1.82, FR: HR 0.78, 95% CI 0.48-1.27]. Among 731 patients undergoing early (5 days, interquartile range 2-29) post-TAVR flow assessment, SVi recovered in 40.1% and FR in 49.0% patients with baseline low flow. Reduced FR following TAVR was an independent predictor of mortality (HR 1.67, 95% CI 1.02-2.74), whereas SVi was not (HR 0.97, 95% CI 0.53-1.78). Three-year estimated mortality in patients with recovered FR was lower than that in patients with reduced FR (13.3 vs. 37.7% vs, P = 0.003) and similar to that in patients with normal baseline FR (P = 0.317). CONCLUSION: Baseline flow status was not an independent predictor of mid-term mortality among all-comers with severe AS undergoing TAVR. Flow recovery early after TAVR was frequent. Post-TAVR FR, but not SVi, was independently associated with mid-term all-cause mortality. By impacting flow status, AV replacement modifies the association of flow status with outcomes.

Efficacy and safety of colchicine for the prevention of major cardiovascular and cerebrovascular events in patients with coronary artery disease: a systematic review and meta-analysis on 12 869 patients.

AIMS: The key role of inflammation in the pathogenesis of coronary artery disease (CAD) is an urgent call for innovative treatments. Several trials have proposed colchicine as a therapeutic option for secondary prevention in CAD patients but its utilization is hampered by fears about drug-related adverse events (DAEs) and conflicting evidences. The aim of this meta-analysis was to consolidate evidence on the efficacy and safety of colchicine for secondary prevention in patients with CAD. METHODS AND RESULTS: A systematic search in electronic bibliographic databases of Medline, Scopus, Embase, and the Cochrane Library was performed to identify randomized controlled trials (RCTs) assessing the cardiovascular effects of colchicine in CAD patients, compared with placebo. Outcomes of interest were the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) and DAEs. Estimates were pooled using inverse-variance random-effects model. A total of 11 RCTs, including 12 869 patients, were identified as eligible. A total of 6501 patients received colchicine, while 6368 received placebo. After a median follow-up of 6 months (interquartile range, 1-16), patients receiving colchicine had a lower risk of MACCE [6% vs. 8.8%, relative risk (RR) = 0.67, 95% confidence interval (CI) 0.56-0.80, I2 = 19%], myocardial infarction (3.3% vs. 4.3%, RR = 0.76, 95% CI 0.61-0.96, I2 = 17%), coronary revascularization (2.9% vs. 4.2%, RR = 0.61, 95% CI 0.42-0.89, I2 = 40%), stroke (0.4% vs. 0.9%, RR = 0.48, 95% CI 0.30-0.77, I2 = 0%), hospitalization for cardiovascular cause (0.9% vs. 2.9%, RR = 0.32, 95% CI 0.12-0.87, I2 = 0%). Colchicine was associated with an increased risk of gastrointestinal DAEs (11% vs. 9.2%, RR = 1.67, 95% CI 1.20-2.34, I2 = 76%), myalgia (18% vs. 16%, RR = 1.16, 95% CI 1.02-1.32, I2 = 0%) and DAEs-related discontinuation (4.1% vs. 3%, RR = 1.54, 95% CI 1.02-2.32, I2 = 65%). However, gastrointestinal DAEs and discontinuation may be prevented with a lower daily dose. Colchicine did not increase the risk of cardiovascular death (0.7% vs. 1%, RR = 0.73, 95% CI 0.45-1.21, I2 = 14%), all-cause death (2% vs. 1.9%, RR = 1.01, 95% CI 0.71-1.43, I2 = 16%), or other DAEs. CONCLUSIONS: The use of colchicine in patients with CAD is safe and efficacious for MACCE prevention.

Impact of lipid-lowering therapies on cardiovascular outcomes according to coronary artery calcium score. A systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: Coronary artery calcium (CAC) score improves the accuracy of risk stratification for atherosclerotic cardiovascular disease (ASCVD) events compared with traditional cardiovascular risk factors. We evaluated the interaction of coronary atherosclerotic burden as determined by the CAC score with the prognostic benefit of lipid-lowering therapies in the primary prevention setting. METHODS: We reviewed the MEDLINE, EMBASE, and Cochrane databases for studies including individuals without a previous ASCVD event who underwent CAC score assessment and for whom lipid-lowering therapy status stratified by CAC values was available. The primary outcome was ASCVD. The pooled effect of lipid-lowering therapy on outcomes stratified by CAC groups (0, 1-100,> 100) was evaluated using a random effects model. RESULTS: Five studies (1 randomized, 2 prospective cohort, 2 retrospective) were included encompassing 35 640 individuals (female 38.1%) with a median age of 62.2 [range, 49.6-68.9] years, low-density lipoprotein cholesterol level of 128 (114-146) mg/dL, and follow-up of 4.3 (2.3-11.1) years. ASCVD occurrence increased steadily across growing CAC strata, both in patients with and without lipid-lowering therapy. Comparing patients with (34.9%) and without (65.1%) treatment exposure, lipid-lowering therapy was associated with reduced occurrence of ASCVD in patients with CAC> 100 (OR, 0.70; 95%CI, 0.53-0.92), but not in patients with CAC 1-100 or CAC 0. Results were consistent when only adjusted data were pooled. CONCLUSIONS: Among individuals without a previous ASCVD, a CAC score> 100 identifies individuals most likely to benefit from lipid-lowering therapy, while undetectable CAC suggests no treatment benefit.

Safety and efficacy of different P2Y12 inhibitors in patients with acute coronary syndromes stratified by the PRAISE risk score: a multicentre study.

AIMS: To establish the safety and efficacy of different dual antiplatelet therapy (DAPT) combinations in patients with acute coronary syndrome (ACS) according to their baseline ischaemic and bleeding risk estimated with a machine learning derived model [machine learning-based prediction of adverse events following an acute coronary syndrome (PRAISE) score]. METHODS AND RESULTS: Incidences of death, re-acute myocardial infarction (re-AMI), and Bleeding Academic Research Consortium 3-5 bleeding with aspirin plus different P2Y12 inhibitors (clopidogrel or potent P2Y12 inhibitors: ticagrelor or prasugrel) were appraised among patients of the PRAISE data set grouped in four subcohorts: low-to-moderate ischaemic and bleeding risk; low-to-moderate ischaemic risk and high bleeding risk; high ischaemic risk and low-to-moderate bleeding risk; and high ischaemic and bleeding risk. Hazard ratios (HRs) for the outcome measures were derived with inverse probability of treatment weighting adjustment. Among patients with low-to-moderate bleeding risk, clopidogrel was associated with higher rates of re-AMI in those at low-to-moderate ischaemic risk [HR 1.69, 95% confidence interval (CI) 1.16-2.51; P = 0.006] and increased risk of death (HR 3.2, 1.45-4.21; P = 0.003) and re-AMI (HR 2.23, 1.45-3.41; P < 0.001) in those at high ischaemic risk compared with prasugrel or ticagrelor, without a difference in the risk of major bleeding. Among patients with high bleeding risk, clopidogrel showed comparable risk of death, re-AMI, and major bleeding vs. potent P2Y12 inhibitors, regardless of the baseline ischaemic risk. CONCLUSION: Among ACS patients with non-high risk of bleeding, the use of potent P2Y12 inhibitors is associated with a lower risk of death and recurrent ischaemic events, without bleeding excess. Patients deemed at high bleeding risk may instead be safely addressed to a less intensive DAPT strategy with clopidogrel.

Impact of computed-tomography defined sarcopenia on outcomes of older adults undergoing transcatheter aortic valve implantation.

BACKGROUND: The adoption of Computed tomography (CT)-defined sarcopenia to risk stratify transcatheter aortic valve implantation (TAVI) candidates remains limited by a lack of both standardized definition and evidence of independent value over currently adopted mortality prediction tools. METHODS: 391 consecutive TAVI patients with pre-procedural CT scan were included (81 â€‹± â€‹6 years, 57.5% male, STS-PROM score 4.4 â€‹± â€‹3.6%) and abdominal muscle retrospectively quantified. The two definitions of radiologic sarcopenia previously adopted in TAVI studies were compared (psoas muscle area [PMA] at the L4 vertebra level: "PMA-sarcopenia"; indexed skeletal muscle area at the L3 vertebra level: "SMI-sarcopenia"). The primary endpoint was longer available-term all-cause mortality. Secondary endpoints were Valve Academic Research Consortium-2-defined in-hospital and 30-day outcomes. RESULTS: SMI- and PMA-sarcopenia were present in 192 (49.1%) and 117 (29.9%) patients, respectively. After a median of 24 (12-30) months follow-up, 83 (21.2%) patients died. PMA-(adj-HR 1.81, 95%CI 1.12-2.93, p â€‹= â€‹0.015), but not SMI-sarcopenia (adj-HR 1.23, 95%CI 0.76-2.00, p â€‹= â€‹0.391), was associated with all-cause mortality independently of age, sex and in-study outcome predictors (atrial fibrillation, hemoglobin, history of peripheral artery disease, cancer and subcutaneous adipose tissue). PMA-defined sarcopenia provided additive prognostic value over current post-TAVI mortality risk estimators including STS-PROM (p â€‹= â€‹0.001), Euroscore II (p â€‹= â€‹0.025), Charlson index (p â€‹= â€‹0.025) and TAVI2-score (p â€‹= â€‹0.020). Device success, early safety, clinical efficacy and 30-day all-cause death were unaffected by sarcopenia status regardless of definition. CONCLUSIONS: PMA-sarcopenia (but not SMI-sarcopenia) is predictive of 2 year mortality among TAVI patients. The prognostic information provided by PMA-sarcopenia is independent of the tools currently adopted to predict post-TAVI mortality in clinical practice.

Prediction of All-Cause Mortality Following Percutaneous Coronary Intervention in Bifurcation Lesions Using Machine Learning Algorithms.

Stratifying prognosis following coronary bifurcation percutaneous coronary intervention (PCI) is an unmet clinical need that may be fulfilled through the adoption of machine learning (ML) algorithms to refine outcome predictions. We sought to develop an ML-based risk stratification model built on clinical, anatomical, and procedural features to predict all-cause mortality following contemporary bifurcation PCI. Multiple ML models to predict all-cause mortality were tested on a cohort of 2393 patients (training, n = 1795; internal validation, n = 598) undergoing bifurcation PCI with contemporary stents from the real-world RAIN registry. Twenty-five commonly available patient-/lesion-related features were selected to train ML models. The best model was validated in an external cohort of 1701 patients undergoing bifurcation PCI from the DUTCH PEERS and BIO-RESORT trial cohorts. At ROC curves, the AUC for the prediction of 2-year mortality was 0.79 (0.74-0.83) in the overall population, 0.74 (0.62-0.85) at internal validation and 0.71 (0.62-0.79) at external validation. Performance at risk ranking analysis, k-center cross-validation, and continual learning confirmed the generalizability of the models, also available as an online interface. The RAIN-ML prediction model represents the first tool combining clinical, anatomical, and procedural features to predict all-cause mortality among patients undergoing contemporary bifurcation PCI with reliable performance.

Adverse events of colchicine for cardiovascular diseases: a comprehensive meta-analysis of 14 188 patients from 21 randomized controlled trials.

AIMS: Colchicine has an emerging role in the cardiovascular field, although, concerns for side effects, especially gastrointestinal, limit its prescription. We aimed at evaluating reported side effects of colchicine for cardiovascular indications. METHODS: We performed a meta-analysis of published randomized controlled trials on colchicine for the treatment of cardiovascular diseases. Random-effects meta-analysis was used to assess the risk of adverse events and drug withdrawal. Publication bias was assessed using the Egger test, and meta-regression was performed to assess sources of heterogeneity. RESULTS: Among 14 188 patients, 7136 patients received colchicine while the other 7052 received placebo. The occurrence of any adverse event with colchicine was reported in 15.3 vs. 13.9% patients [relative risk (RR) 1.26, 95% confidence interval (CI) 0.96-1.64, P = 0.09]. Gastrointestinal events were reported in 16.1 vs. 12.2% (RR 2.16, 95% CI 1.50-3.12, P < 0.001), while diarrhea was reported in 12.5 vs. 8.1% (RR 2.77, 95% CI 1.55-4.94, P < 0.001). The risk of gastrointestinal events increased with daily dose and shorter treatment duration. Myalgias were observed in 21 vs. 18% patients (RR 1.16, 95% CI 1.02-1.32, P = 0.03). Other adverse events such as myotoxicity, hepatic adverse events, hematologic adverse events, cutaneous adverse events, infection or death were not increased by colchicine treatment. Colchicine discontinuation was reported in 4.8 vs. 3.4% patients (RR 1.54, 95% CI 1.20-1.99, P < 0.001). CONCLUSION: Colchicine is associated with increased risk of gastrointestinal events and myalgias, but not of other adverse events. The risk of gastrointestinal events may be avoided with lower dose (0.5 mg/daily) and is inversely related to treatment duration, possibly due to early drug discontinuation or drug tolerance.