Application of the Academic Research Consortium High Bleeding Risk criteria in patients treated with coronary bioresorbable polymer everolimus-eluting stents: Insights from the POEM trial.

BACKGROUND: Previous studies have investigated a 1 to 6-month short dual antiplatelet therapy (S-DAPT) after percutaneous coronary intervention (PCI) with modern drug eluting-stents to reduce bleeding events. OBJECTIVES: To investigate cardiovascular outcomes in patients at high bleeding risk (HBR) according to the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria after PCI with the Synergy bioresorbable-polymer everolimus-eluting stents (EES). METHODS: We applied ARC-HBR criteria in the population of the prospective, single-arm, multicenter POEM (Performance of Bioresorbable Polymer-Coated Everolimus-Eluting Synergy Stent in Patients at HBR Undergoing Percutaneous Coronary Revascularization Followed by 1-Month Dual Antiplatelet Therapy) trial. The primary endpoint was a composite of cardiac death, myocardial infarction, or definite or probable stent thrombosis at 12 months. RESULTS: The original POEM cohort included 356 patients (80.4 %) fulfilling ARC-HBR criteria. Oral anticoagulant (OAC) usage and age ≥75 years were the most frequent major and minor ARC-HBR criteria, respectively. The ARC-HBR group was mainly represented by men (71.1 %), with 74.4 ± 9.3 years and a high burden of cardiovascular risk factors. DAPT was prescribed in 79.3 %, and single antiplatelet (SAPT) with OAC in 18.7 %. 12-month follow-up was completed in 96.2 %. The primary endpoint occurred in 5.2 % (95 % CI 3.29-8.10) of patients, whereas bleeding Academic Research Consortium type 3-5 occurred in 2.7 % (95 % CI, 1.39 %-5.05 %). CONCLUSION: Previous results of the POEM trial showed positive outcomes regarding ischemic and bleeding events with an S-DAPT regimen after Synergy EES. These results are also confirmed in sub-group analysis when ARC-HBR criteria are applied.

Bileaflet Tethering With Preserved LV Geometry and Function: An Unusual Mechanism of Functional Mitral Regurgitation.

An 81-year-old woman presented with acute pulmonary edema. Echocardiography revealed severe functional mitral regurgitation, the mechanism of which was unusual. An atypical bileaflet tethering caused by disharmonic annular remodeling, concomitant aortic dilatation, and reduced aorto-mitral angle without left ventricular dysfunction or dilatation was found. A transcatheter edge-to-edge repair was nonetheless successfully performed.

Update on long-term cardiovascular risk after pre-eclampsia: a systematic review and meta-analysis.

BACKGROUND/INTRODUCTION: There is a need for further studies on the cardiovascular risk of women experiencing pre-eclampsia (PE). PURPOSE: To update the literature regarding the association between a history of PE and subsequent cardiovascular diseases, including cardiovascular death, coronary heart diseases, heart failure, and stroke, focusing on the trend in the effect size (ES) estimates over time. METHODS AND RESULTS: Following PRISMA guidelines, from inception to May 2023, we performed a systematic review of PubMed, MEDLINE, Scopus, and EMBASE. Randomized, cohort, or case-control studies in English were included if fulfiling the following criteria:(i) The association between PE and subsequent cardiovascular disease was adjusted for clinically relevant variables, (ii) the presence of a control group, and (iii) at least 1 year of follow-up. Pooled adjusted ESs and 95% confidence intervals (CIs) were used as effect estimates and calculated with a random-effect model. Twenty-two studies met the inclusion criteria. PE was associated with a higher risk of cardiovascular death (ES 2.08, 95% CI 1.70-2.54, I2 56%, P < 0.00001), coronary artery diseases (ES 2.04, 95% CI 1.76-2.38, I2 87%, P < 0.00001), heart failure (ES 2.47, 95% CI 1.89-3.22, I2 83%, P < 0.00001), and stroke (ES 1.75, 95% CI 1.52-2.02, I2 72%, P < 0.00001) after adjusting for potential confounders. This risk is evident in the first 1-to-3 years of follow-up and remains significant until 39 years of follow-up. CONCLUSIONS: Compared to women who experienced a normal pregnancy, those suffering from PE have about double the risk of lifetime cardiovascular disease.

Dyspnea-Related Ticagrelor Discontinuation After Percutaneous Coronary Intervention.

BACKGROUND: Nearly 20% of patients on ticagrelor experience dyspnea, which may lead to treatment discontinuation in up to one-third of cases. OBJECTIVES: The authors sought to evaluate the incidence, predictors, and outcomes of dyspnea-related ticagrelor discontinuation after percutaneous coronary intervention (PCI). METHODS: In the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) trial, after 3 months of ticagrelor plus aspirin, patients were maintained on ticagrelor and randomized to aspirin or placebo for 1 year. The occurrence of dyspnea associated with ticagrelor discontinuation was evaluated among all patients enrolled in the trial. A landmark analysis was performed at 3 months after PCI, that is, the time of randomization. Predictors of dyspnea-related ticagrelor discontinuation were obtained from multivariable Cox regression with stepwise selection of candidate variables. RESULTS: The incidence of dyspnea-related ticagrelor discontinuation was 6.4% and 9.1% at 3 and 15 months after PCI, respectively. Independent predictors included Asian race (lower risk), smoking, prior PCI, hypercholesterolemia, prior coronary artery bypass, peripheral artery disease, obesity, and older age. Among 179 patients who discontinued ticagrelor because of dyspnea after randomization, ticagrelor monotherapy was not associated with a higher risk of subsequent ischemic events (composite of all-cause death, myocardial infarction, or stroke) compared with ticagrelor plus aspirin (5.0% vs 7.1%; P = 0.566). CONCLUSIONS: In the TWILIGHT trial, dyspnea-related ticagrelor discontinuation occurred in almost 1 in 10 patients and tended to occur earlier rather than late after PCI. Several demographic and clinical conditions predicted its occurrence, and their assessment may help identify subjects at risk for therapy nonadherence.

One-Month Dual Antiplatelet Therapy in Patients With Chronic and Acute Coronary Syndromes Treated With Bioresorbable Polymer Everolimus-Eluting Stents.

There is a paucity of data regarding the safety of a 1-month dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in patients at high bleeding risk (HBR) presenting with acute coronary syndromes (ACS). We aimed to compare the clinical outcomes of patients at HBR with chronic coronary syndrome (CCS) or ACS treated with PCI using bioresorbable polymer everolimus-eluting stent (BP-EES) followed by 1-month DAPT. Patients at HBR who underwent PCI with BP-EES were prospectively enrolled in 10 Italian centers. All patients were treated with 1-month DAPT. In case of need for anticoagulation, patients received an oral anticoagulant in addition to a P2Y12 inhibitor for 1 month, followed by oral anticoagulation only after that. The primary end point was a composite of cardiac death, myocardial infarction, or definite/probable stent thrombosis at 12 months. Overall, 263 patients (59.4%) with CCS and 180 patients (40.6%) with ACS were enrolled. No significant difference was evident between patients with CCS and ACS for the primary end point (4.3% vs 5.6%, respectively, p = 0.497) and for each isolated component. The risk for Bleeding Academic Research Consortium (BARC) type 1 to 5 or type 3 to 5 bleedings was also similar between patients with CCS and ACS (4.3% vs 5.2%, p = 0.677, and 1.6% vs 2.9%, p = 0.351, respectively). In conclusion, among HBR patients with ACS who underwent PCI with BP-EES, a 1-month DAPT strategy is associated with a similar risk of ischemic and bleeding events compared with those with CCS.

Prognostic value of high-sensitivity C-reactive protein among chronic kidney disease patients undergoing percutaneous coronary intervention.

BACKGROUND: Data on the prognostic value of high-sensitivity C-reactive protein (hs-CRP) levels in patients with chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI) are limited. METHODS: Patients undergoing PCI at a tertiary center from January 2012 to December 2019 were included. CKD was defined as a glomerular filtration rate (GFR) <60 mL/min/1.73m2 and elevated hs-CRP was defined as >3 mg/L. Acute myocardial infarction (MI), acute heart failure, neoplastic disease, patients undergoing hemodialysis, or hs-CRP >10 mg/L were exclusion criteria. The primary outcome was major adverse cardiac events (MACE), a composite of all-cause death, MI, and target vessel revascularization at 1-year after PCI. RESULTS: Out of 12,410 patients, 3029 (24.4 %) had CKD. Elevated hs-CRP levels were found in 31.8 % of CKD and 25.8 % of no-CKD patients. At 1 year, MACE occurred in 87 (11.0 %) CKD patients with elevated hs-CRP and 163 (9.5 %) with low hs-CRP (adj. HR 1.26, 95 % CI 0.94-1.68); among no-CKD patients, in 200 (10 %) and 470 (8.1 %), respectively (adj. HR 1.21, 95 % CI 1.00-1.45). Hs-CRP was associated with an increased risk of all-cause death in both CKD (Adj. HR 1.92, 95 % CI 1.07-3.44) and no-CKD patients (adj. HR 3.02, 95 % CI 1.74-5.22). There was no interaction between hs-CRP and CKD status. CONCLUSIONS: Among patients undergoing PCI without acute MI, elevated hs-CRP values were not associated with a higher risk of MACE at 1 year, but with increased mortality hazards consistently in patients with or without CKD.

Evolution of drug-eluting coronary stents: a back-and-forth journey from the bench to bedside.

Coronary stents have revolutionized the treatment of coronary artery disease. Compared with balloon angioplasty, bare-metal stents (BMSs) effectively prevented abrupt vessel closure but were limited by in-stent restenosis (ISR) due to smooth muscle cell proliferation and neointimal hyperplasia. The first-generation drug-eluting stent (DES), with its antiproliferative drug coating, offered substantial advantages over BMSs as it mitigated the risk of ISR. Nonetheless, they had several design limitations that increased the risk of late stent thrombosis. Significant advances in stent design, including thinner struts, enhanced polymers' formulation, and more potent antiproliferative agents, have led to the introduction of new-generation DES with a superior safety profile. Cardiologists have over 20 different DES types to choose from, each with its unique features and characteristics. This review highlights the evolution of stent design and summarizes the clinical data on the different stent types. We conclude by discussing the clinical implications of stent design in high-risk subsets of patients.

New Criteria to Identify Patients at Higher Risk for Cardiovascular Complications After Percutaneous Coronary Intervention.

A universal definition to identify patients at higher risk of complications after percutaneous coronary intervention (PCI) is lacking. We aimed to validate a recently developed score to identify patients at increased risk of all-cause death after PCI. All consecutive patients from a large PCI registry not presenting with ST-elevation myocardial infarction or cardiogenic shock were included. Each patient was assigned a score obtained by summing the points associated with the following variables: age >80 years (3 points), dialysis (6 points), left ventricular ejection fraction <30% (2 points), and multivessel PCI (2 points). Patients were stratified in 3 groups: low risk (score 0), intermediate risk (score 2 to 3), or high risk (score ≥4). The primary outcome was all-cause death, and the secondary outcomes were major adverse cardiovascular events and major bleeding. Events were assessed at 1 year after PCI. Between January 2014 and December 2019, 12,689 patients underwent PCI. Compared with the 9,884 patients at low risk, those at intermediate and high risk had a fourfold (hazard ratio 3.99, 95% confidence interval 2.95 to 5.38) and ninefold (hazard ratio 9.55, 95% confidence interval 6.89 to 13.2) higher hazard for all-cause death at 1 year, respectively. The score had a good predictive value for all-cause death at 1 year (area under the curve 0.70). The risk of major adverse cardiovascular events and major bleeding increased consistently from the low- to the high-risk group. In conclusion, in patients who underwent PCI for stable ischemic heart disease or non-ST-elevation acute coronary syndrome, a score based on 4 variables well predicted the risk of all-cause death at 1 year.

Efficacy and safety of P2Y12 inhibitor monotherapy after complex PCI: a collaborative systematic review and meta-analysis.

AIMS: Complex percutaneous coronary intervention (C-PCI) is associated with an increased risk of ischaemic and bleeding complications. We aimed to assess the safety and efficacy of a 1-3-month dual antiplatelet therapy (DAPT) regimen followed by P2Y12 inhibitor monotherapy after C-PCI. METHODS AND RESULTS: We conducted a meta-analysis of randomized trials comparing a 1-3-month DAPT regimen followed by P2Y12 inhibitor monotherapy with standard (≥12 months) DAPT in patients undergoing C-PCI. C-PCI criteria and the co-primary bleeding and ischaemic outcomes were determined according to each trial. Secondary outcomes included major bleeding, all-cause death, myocardial infarction, and stent thrombosis. All outcomes were evaluated at 12 months after randomization. We used hazard ratios (HRs) and 95% confidence interval (CI) as a metric of choice for treatment effects with random-effects models. Among 8299 screened studies, five randomized trials fulfilled the eligibility criteria. In the pooled population of 34 615 patients, 8818 (25.5%) underwent C-PCI. As compared with standard DAPT, a 1-3-month DAPT regimen followed by P2Y12 inhibitor monotherapy reduced the bleeding risk in C-PCI (HR:0.66, 95% CI:0.44-0.98) and non-C-PCI (HR:0.60, 95% CI:0.45-0.79) patients (P-interaction = 0.735). Furthermore, the risk for the primary ischaemic endpoint was similar in patients randomized to either arm, with significant effect modification by PCI complexity showing an enhanced benefit of 1-3-month DAPT in patients undergoing C-PCI (C-PCI, HR:0.69, 95% CI:0.48-1.00; non-C-PCI, HR:1.04, 95% CI:0.84-1.30; P-interaction = 0.028). CONCLUSION: As compared with a standard DAPT, a 1-3-month DAPT regimen followed by P2Y12 inhibitor monotherapy reduced bleeding complications after C-PCI without increasing the risk of ischaemic events.PROSPERO-registered (CRD42021259271).

The mega COMBO collaboration: An individual patient data pooled analysis of patients undergoing PCI with COMBO stent.

BACKGROUND: COMBO (OrbusNeich Medical, Hong Kong) is a dual-therapy coronary stent featuring sirolimus as antiproliferative drug and an anti-CD34+ antibody coating to attract endothelial progenitor cells favoring rapid stent re-endothelization. The Mega COMBO collaboration aimed to evaluate the performance of the COMBO stent in a large contemporary cohort of patients undergoing percutaneous coronary intervention (PCI). METHODS: Patient-level data of subjects undergoing PCI with the COMBO stent from the REMEDEE-Trial, REMEDEE-OCT, HARMONEE, REDUCE, SORT OUT X, REMEDEE-Registry and MASCOT studies were pooled together. The primary endpoint was 1-year target lesion failure (TLF), a composite of cardiovascular death, target vessel myocardial infarction (TV-MI) or clinically driven target lesion revascularization (CD-TLR). Secondary outcomes were the individual components of the primary endpoint and stent thrombosis (ST). Endpoints were evaluated against performance goals based on the EAPCI (the European Association of Percutaneous Coronary Intervention) recommendations for new drug-eluting stents. RESULTS: A total of 6753 patients (mean age 63.7 ± 11.4 years, 23% women) were included. At 1-year follow-up, TLF occurred in 303 (4.6%) patients. The rates of cardiovascular death, TV-MI, and CD-TLR were 1.3%, 1.8%, and 2.5%, respectively. The rate of definite/probable ST was 0.73%, early ST (<1 month) was 0.48%, while late ST (1-12 months) was 0.26%. The performance goals were met for all of the evaluated endpoints. CONCLUSIONS: This large patient-level pooled analysis provides a comprehensive outline of the performance of the dual-therapy COMBO stent. The low rates of primary and secondary endpoints suggest that this stent technology may be a good alternative to other contemporary drug eluting coronary stent platforms.

Bleeding and Ischemic Outcomes With Ticagrelor Monotherapy According to Body Mass Index.

BACKGROUND: There is a paucity of data regarding the safety and efficacy of different antiplatelet regimens according to standardized body mass index (BMI) categories. OBJECTIVES: The aim of this study was to investigate bleeding and ischemic outcomes according to BMI in the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) trial. METHODS: The TWILIGHT trial randomized high-risk patients to ticagrelor plus aspirin or ticagrelor plus placebo at 3 months after percutaneous coronary intervention. In this secondary analysis, patients were stratified by standard BMI categories, as recommended by the European Society of Cardiology Working Group on Thrombosis (normal weight [BMI 18.5-24.99 kg/m2], overweight [BMI 25-29.99 kg/m2], and obese [BMI ≥30 kg/m2]) and by median BMI, as prespecified in the protocol. RESULTS: Among 7,038 patients randomized and with available BMI, 1,807 (25.7%) were normal weight, 2,927 (41.6%) were overweight, and 2,304 (32.7%) were obese. In normal-weight, overweight, and obese patients, ticagrelor monotherapy, compared with ticagrelor plus aspirin, reduced the primary endpoint of Bleeding Academic Research Consortium type 2, 3, or 5 bleeding (normal weight: HR: 0.48 [95% CI: 0.32-0.73]; overweight: HR: 0.57 [95% CI: 0.41-0.78]; obese: HR: 0.63 [95% CI: 0.44-0.91]; P for interaction = 0.627), without any increase in the composite ischemic endpoint of all-cause death, myocardial infarction, or stroke (normal weight: HR: 1.36 [95% CI: 0.84-2.19]; overweight: HR: 0.92 [95% CI: 0.63-1.35]; obese: HR: 0.84 [95% CI: 0.56-1.25]; P for interaction = 0.290). These findings were consistent with the prespecified analysis by median BMI. CONCLUSIONS: Among high-risk patients undergoing percutaneous coronary intervention, ticagrelor monotherapy, compared with ticagrelor plus aspirin, reduced bleeding events without any increase in ischemic risk across different BMI categories.

Left atrial appendage closure with the II generation Ultraseal device: An international registry. The LIGATE study.

OBJECTIVES: To assess feasibility and safety of second-generation left atrial appendage closure (LAAC) Ultraseal device in patients with nonvalvular atrial fibrillation (NVAF). BACKGROUND: LAAC with first-generation Ultraseal device (Cardia, Eagan, Minnesota) has been shown to be a feasible therapeutic option in patients with NVAF. However, there is a paucity of data regarding the novel second-generation Ultraseal device. METHODS: All patients with NVAF undergoing second-generation Ultraseal device implantation between February 2018 and September 2020 were included in a multicenter international registry. Periprocedural and post-discharge events were collected through 6-month follow-up. Co-primary efficacy endpoints were device success and technical success while primary safety endpoint was in-hospital major adverse event (MAE) occurrence. RESULTS: A total of 52 patients were included: mean age 75 ± 8, 30.8% women, mean HAS-BLED 3 ± 1. The device was successfully implanted in all patients. Technical success was achieved in 50 patients (96.1%). In-hospital MAEs occurred in three patients (5.8%). The incidence of 6-month all-cause death and major bleeding was 11.6% and 2.1%, respectively. No strokes, transient ischemic attacks, systemic embolisms, or device embolization were reported after discharge. CONCLUSIONS: Second-generation Ultraseal device implantation was associated with high success rates and a low incidence of peri-procedural complications. Larger studies with longer follow-up are warranted to further evaluate the safety and the efficacy of this device, especially at long-term follow-up.

Depression and ischemic heart disease.

Depression is common in patients with ischemic heart disease, and depressed patients are more likely to develop atherosclerosis and experience major cardiac events compared with the general population. The underlying pathophysiological mechanisms of these two diseases are highly interwoven and include an increased release of stress hormones, dysregulation of the autonomic nervous system, alterations of pathways related to primary and secondary hemostasis, endothelial dysfunction, and higher level of residual inflammation. Furthermore, depression negatively impacts compliance with medication regimens. As such, early recognition and treatment of depression provide the opportunity to improve outcomes of patients with ischemic heart disease. In the present review, we provide a summary of the evidence on the epidemiology, pathophysiology and management of depression in patients with ischemic heart disease.

Pericardial Effusion Provoking Atrial Fibrillation After Cardiac Surgery: JACC Review Topic of the Week.

Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery. Patients who develop POAF are more likely to experience adverse outcomes, including increased rates of death, stroke, heart failure, and hospitalizations, and higher hospital costs. Understanding the mechanisms underlying POAF is important to improve patients' outcome and optimize health systems' efficiency. Beyond classic pathogenic hypotheses, emerging evidence suggests that postoperative pericardial effusion and localized pericardial inflammation may trigger POAF. This hypothesis is supported by data from nonhuman animal models and a growing body of evidence showing that reducing postoperative pericardial effusion might reduce POAF incidence. In this review, we summarize the classic pathophysiology theories of POAF following cardiac surgery and discuss new etiologic mechanisms with a specific focus on the role of pericardial effusion and inflammation.

Impact of Small Valve Size on 1-Year Outcomes After Transcatheter Aortic Valve Implantation in Women (from the WIN-TAVI Registry).

Although most patients with small aortic annulus are women, there is paucity of data on the prognostic impact of small aortic prosthesis in women who underwent transcatheter aortic valve implantation (TAVI). Therefore, we aimed to evaluate the impact of small valve size on 1-year clinical outcomes after TAVI in women. The Women's INternational Transcatheter Aortic Valve Implantation is an all-women registry evaluating patients with severe aortic stenosis who underwent TAVI. Based on the size of the aortic bioprosthesis implanted, women were stratified into small (≤23 mm) and nonsmall (>23 mm) valve. The primary efficacy endpoint was the Valve Academic Research Consortium-2 composite of all-cause death, stroke, myocardial infarction, hospitalization for valve-related symptoms or heart failure or valve-related dysfunction at 1-year follow-up. Of 934 women who underwent TAVI, 388 (41.5%) received a small valve. Women with a small valve size had a lower body mass index, lower surgical risk scores, were less likely to suffer from atrial fibrillation, less often required postdilation and had a lower rate of residual aortic regurgitation grade ≥2. The occurrence of the Valve Academic Research Consortium-2 efficacy endpoint was similar between women treated with small and nonsmall valve (16.0% vs 16.3%, p = 0.881; adjusted hazard ratio 1.34, 95% confidence interval 0.90 to 2.00). Likewise, there were no significant differences in the occurrence of other secondary endpoints after multivariable adjustment. In conclusion, women with severe aortic stenosis who underwent TAVI with the implantation of a small valve bioprosthesis had similar 1-year outcomes as those receiving a nonsmall bioprosthesis.

Perioperative management of P2Y12 inhibitors in patients undergoing cardiac surgery within 1 year of PCI.

AIMS: To evaluate the impact of perioperative P2Y12 receptor inhibitor therapy among patients undergoing cardiac surgery within 1 year of percutaneous coronary intervention (PCI). METHODS AND RESULTS: Patients undergoing cardiac surgery in the year post-PCI at three tertiary care centres between 2011 and 2018 were stratified into those who had received at least one dose of P2Y12 inhibitor prior to surgery (within 5 days for clopidogrel or prasugrel, or within 3 days for ticagrelor) and those who had not. The outcomes of interest were major adverse cardiac and cerebrovascular events (MACCEs) and bleeding. Among 20 279 PCI patients, 359 (1.8%) underwent cardiac surgery in the ensuing year, 76.3% of whom received coronary artery bypass grafts. Overall, 33 (9.2%) MACCEs and 85 (23.7%) bleeding events occurred within 30 days post-cardiac surgery. Perioperative P2Y12 inhibition (N = 133, 37%) was not associated with the risk of MACCEs or bleeding, despite numerically lower rates of myocardial infarction or stent thrombosis (0.0% vs. 2.6%; P = 0.089). Patients who continued the P2Y12 inhibitor until the day of surgery (N = 60, 17%) had significantly higher bleeding risk [adjusted odds ratio 2.93, 95% confidence interval 1.53-5.59)]. Predictors of MACCEs included a time interval from PCI to cardiac surgery of ≤30 days and reduced ejection fraction, whereas urgent/emergent surgery predicted bleeding. Chronic kidney disease and myocardial infarction as indication for PCI predicted both MACCEs and bleeding. CONCLUSION: Among patients undergoing cardiac surgery in the year after PCI, the perioperative risk of ischaemic and bleeding events might be influenced by P2Y12 inhibitor therapy in addition to other risk parameters, including the timing and urgency of the procedure.

Effect of Chronic Kidney Disease on 5-Year Outcome in Patients With Heart Failure and Secondary Mitral Regurgitation Undergoing Percutaneous MitraClip Insertion.

Chronic kidney disease (CKD) is strongly related to outcomes in cardiovascular diseases. Limited data are available regarding the independent prognostic role of CKD after transcatheter mitral valve repair with MitraClip. We sought to evaluate the real impact of CKD in a large series of patients with heart failure (HF) and secondary mitral regurgitation (SMR) who underwent MitraClip treatment. The study included 565 patients with severe SMR from a multicenter international registry. Patients were stratified into 3 groups according to estimated glomerular filtration rate (eGFR) assessment before MitraClip implantation: normal eGFR (≥60 ml/min/1.73 m2) (n = 196), mild-to-moderate CKD (30 to 59 ml/min/1.73 m2) (n = 267), and severe CKD (<30 ml/min/1.73 m2) (n = 102). The primary end point was a composite of overall death and the first rehospitalization for HF, the secondary end points were overall death, cardiac death, and first rehospitalization for HF. CKD was present in about 2/3 of patients. At 5-year Kaplan-Meier analysis, primary clinical end point occurred in 60% of patients with normal eGFR, compared with 73% cases in patients with mild-to-moderate CKD and 91% in patients with severe CKD (p <0.001). Long-term overall death rate significantly decreased with increasing eGFR, and cardiac death and rehospitalization for HF rates. Multivariate Cox regression analysis identified severe CKD as the strongest independent predictor of adverse outcome (hazard ratio 2.136, 95% confidence interval 1.164 to 3.918, p = 0.014). In conclusion, CKD affected about 2/3 of patients who underwent MitraClip treatment for severe SMR, and it was a strong and independent predictor of 5-year adverse outcomes.

Ticagrelor monotherapy after PCI in patients with concomitant diabetes mellitus and chronic kidney disease: TWILIGHT DM-CKD.

AIMS: We aimed to evaluate the treatment effects of ticagrelor monotherapy in the very high risk cohort of patients with concomitant diabetes mellitus (DM) and chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: In the TWILIGHT (Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial, after 3-month dual antiplatelet therapy with ticagrelor and aspirin post-PCI, event-free patients were randomized to either aspirin or placebo in addition to ticagrelor for 12 months. Those with available information on DM and CKD status were included in this subanalysis and were stratified by the presence or absence of either condition: 3391 (54.1%) had neither DM nor CKD (DM-/CKD-), 1822 (29.0%) had DM only (DM+/CKD-), 561 (8.9%) had CKD only (DM-/CKD+), and 8.0% had both DM and CKD (DM+/CKD+). The incidence of the primary endpoint of Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding did not differ according to DM/CKD status (P-trend = 0.13), but there was a significant increase in BARC 3 or 5 bleeding (P-trend < 0.001) as well as the key secondary endpoint of death, myocardial infarction, or stroke (P-trend < 0.001). Ticagrelor plus placebo reduced bleeding events compared with ticagrelor plus aspirin across all four groups, including DM+/CKD+ patients with respect to BARC 2-5 [4.5% vs. 8.7%; hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.24-1.01] as well as BARC 3-5 (0.8% vs. 5.3%; HR 0.15, 95% CI 0.03-0.53) bleeding, with no evidence of heterogeneity. The risk of death, myocardial infarction, or stroke was similar between treatment arms across all groups. CONCLUSION: Irrespective of the presence of DM, CKD, and their combination, ticagrelor monotherapy reduced the risk of bleeding without a significant increase in ischaemic events compared with ticagrelor plus aspirin.

One-Month Dual Antiplatelet Therapy After Bioresorbable Polymer Everolimus-Eluting Stents in High Bleeding Risk Patients.

Background It is unknown whether contemporary drug-eluting stents have a similar safety profile in high bleeding risk patients treated with 1-month dual antiplatelet therapy following percutaneous coronary interventions. Methods and Results We performed an interventional, prospective, multicenter, single-arm trial, powered for noninferiority with respect to an objective performance criterion to evaluate the safety of percutaneous coronary interventions with Synergy bioresorbable-polymer everolimus-eluting stent followed by 1-month dual antiplatelet therapy in patients with high bleeding risk. In case of need for an oral anticoagulant, patients received an oral anticoagulant in addition to a P2Y12 inhibitor for 1 month, followed by an oral anticoagulant only. The primary end point was the composite of cardiac death, myocardial infarction, or definite or probable stent thrombosis at 1-year follow-up. The study was prematurely interrupted because of slow recruitment. From April 2017 to October 2019, 443 patients (age, 74.8±9.2 years; women, 29.1%) at 10 Italian centers were included. The 1-year primary outcome occurred in 4.82% (95% CI, 3.17%-7.31%) of patients, meeting the noninferiority compared with the predefined objective performance criterion of 9.4% and the noninferiority margin of 3.85% (Pnoninferiority<0.001) notwithstanding the lower-than-expected sample size. The rates of cardiac death, myocardial infarction, and definite or probable stent thrombosis were 1.88% (95% CI, 0.36%-2.50%), 3.42% (95% CI, 2.08%-5.62%), and 0.94% (95% CI, 0.35%-2.49%), respectively. Conclusions Among high bleeding risk patients undergoing percutaneous coronary interventions with the Synergy bioresorbable-polymer everolimus-eluting stent, a 1-month dual antiplatelet therapy regimen is safe, with low rates of ischemic and bleeding events. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03112707.

Prognostic Value of Baseline Inflammation in Diabetic and Nondiabetic Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: There is a paucity of data on the prognostic value of high-sensitivity C-reactive protein (hsCRP) levels in diabetic and nondiabetic patients undergoing percutaneous coronary intervention (PCI). METHODS: All patients with known baseline hsCRP undergoing PCI at a single tertiary care centre from 2010 to 2017 were included. High hsCRP was defined as > 3 mg/L. Known causes of elevated hsCRP levels and hsCRP > 10 mg/L represented exclusion criteria. The 1-year primary outcome was major adverse cardiovascular events (MACE), including all-cause mortality, myocardial infarction (MI), and target-vessel revascularisation (TVR). RESULTS: Among a total of 11,979 patients included, high hsCRP levels were observed in 24.7% of patients without diabetes and 29.8% of patients with diabetes (P < 0.001). Both diabetics and nondiabetics with high hsCRP levels had increased rates of MACE compared with their counterparts with low hsCRP (diabetics: adjusted hazard ratio [aHR] 1.58, 95% CI 1.27-1.96; nondiabetics: aHR 1.45, 95% CI 1.13-1.86; P interaction = 0.981) primarily driven by increased rates all-cause deaths (diabetics: aHR 2.32, 95% CI 1.42-3.80; nondiabetics: aHR 3.14, 95% CI 1.74-5.65; P interaction = 0.415). Although high hsCRP levels were associated with increased rates of TVR (aHR 1.35, 95% CI 1.04-1.75) and MI (aHR 1.86, 95% CI 1.18-2.93) only in patients with diabetes, no significant interactions were observed between inflammation and diabetes (P interaction = 0.749 and 0.602, respectively). CONCLUSIONS: Patients undergoing PCI with high levels of hsCRP, defined as > 3 mg/L, have worse ischemic outcomes regardless of diabetes status.