Angiographic Characteristics and Clinical Outcomes in Patients With Chronic Kidney Disease Undergoing Impella-Supported High-Risk Percutaneous Coronary Intervention: Insights From the cVAD PROTECT III Study.

BACKGROUND: Prior studies have found that patients with chronic kidney disease (CKD) have worse outcomes following percutaneous coronary intervention (PCI). There are no data about patients with advanced CKD undergoing Impella-supported high-risk PCI. We, therefore, aimed to evaluate angiographic characteristics and clinical outcomes in patients with CKD who received Impella-supported high-risk PCI as part of the catheter-based ventricular assist device PROTECT III study (A Prospective, Multi-Center, Randomized Controlled Trial of the IMPELLA RECOVER LP 2.5 System Versus Intra Aortic Balloon Pump [IABP] in Patients Undergoing Non Emergent High Risk PCI). METHODS: Patients enrolled in the PROTECT III study were analyzed according to their baseline estimated glomerular filtration rate (eGFR). The primary outcome was 90-day major adverse cardiovascular and cerebrovascular events (the composite of all-cause death, myocardial infarction, stroke/transient ischemic attack, and repeat revascularization). RESULTS: Of 1237 enrolled patients, 1052 patients with complete eGFR baseline assessment were evaluated: 586 with eGFR ≥60 mL/min per 1.73 m2, 190 with eGFR ≥45 to <60, 105 with eGFR ≥30 to <45, and 171 with eGFR <30 or on dialysis. Patients with lower eGFR (all groups with eGFR <60) were more frequently females and had a higher prevalence of hypertension, diabetes, anemia, and peripheral artery disease. The baseline Synergy Between PCI With Taxus and Cardiac Surgery score was similar between groups (28.2±12.6 for all groups). Patients with lower eGFR were more likely to have severe coronary calcifications and higher usage of atherectomy. There were no differences in individual PCI-related coronary complications between groups, but the rates of overall PCI complications were less frequent among patients with lower eGFR. Major adverse cardiovascular and cerebrovascular events at 90 days and 1-year mortality were significantly higher among patients with eGFR <30 mL/min per 1.73 m2 or on dialysis. CONCLUSIONS: Patients with advanced CKD undergoing Impella-assisted high-risk PCI tend to have higher baseline comorbidities, severe coronary calcification, and higher atherectomy usage, yet CKD was not associated with a higher rate of immediate PCI-related complications. However, 90-day major adverse cardiovascular and cerebrovascular events and 1-year mortality were significantly higher among patients with eGFR<30 mL/min per 1.73 m2 or on dialysis. Future studies of strategies to improve intermediate and long-term outcomes of these high-risk patients are warranted. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04136392.

Statistical primer: individual patient data meta-analysis and meta-analytic approaches in case of non-proportional hazards.

Individual patient data (IPD) meta-analyses build upon traditional (aggregate data) meta-analyses by collecting IPD from the individual studies rather than using aggregated summary data. Although both traditional and IPD meta-analyses produce a summary effect estimate, IPD meta-analyses allow for the analysis of data to be performed as a single dataset. This allows for standardization of exposure, outcomes, and analytic methods across individual studies. IPD meta-analyses also allow the utilization of statistical methods typically used in cohort studies, such as multivariable regression, survival analysis, propensity score matching, uniform subgroup and sensitivity analyses, better management of missing data, and incorporation of unpublished data. However, they are more time-intensive, costly, and subject to participation bias. A separate issue relates to the meta-analytic challenges when the proportional hazards assumption is violated. In these instances, alternative methods of reporting time-to-event estimates, such as restricted mean survival time should be used. This statistical primer summarizes key concepts in both scenarios and provides pertinent examples.

Impact of Incomplete Revascularization After PCI in Left Main Disease: The EXCEL Trial.

BACKGROUND: The importance of complete revascularization after percutaneous coronary intervention (PCI) in patients with left main coronary artery disease is uncertain. We investigated the clinical impact of complete revascularization in patients with left main coronary artery disease undergoing PCI in the EXCEL trial (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization). METHODS: Composite rates of death or myocardial infarction (MI) following PCI during 5-year follow-up were examined in 903 patients based on core laboratory definitions of anatomic and functional complete revascularization, residual SYNTAX score (The Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery), and residual Jeopardy Score (rJS). RESULTS: The risk of death or MI did not vary based on anatomic, functional, or residual SYNTAX score complete revascularization but did differ according to the rJS (5-year rates 17.6%, 19.5%, and 38.9% with rJS 0, 2, and ≥4, respectively; P=0.006). The higher rate of death or MI with rJS≥4 versus rJS≤2 was driven conjointly by increased mortality (adjusted hazard ratio, 2.29 [95% CI, 1.11-4.71]; P=0.02) and spontaneous MI (adjusted hazard ratio, 2.89 [95% CI, 1.17-7.17]; P=0.02). The most common location for untreated severe stenoses in the rJS≥4 group was the left circumflex artery (LCX), and the post-PCI absence, compared with the presence, of any untreated lesion with diameter stenosis ≥70% in the LCX was associated with reduced 5-year rates of death or MI (18.9% versus 35.2%; hazard ratio, 0.48 [95% CI, 0.32-0.74]; P<0.001). The risk was the highest for residual ostial/proximal LCX lesions. CONCLUSIONS: Among patients undergoing PCI in EXCEL trial, incomplete revascularization according to the rJS was associated with increased rates of death and spontaneous MI. Post-PCI untreated high-grade lesions in the LCX (especially the ostial/proximal LCX) drove these outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01205776.

Incidence, Predictors, and Impact of Hospital Readmission After Revascularization for Left Main Coronary Disease.

BACKGROUND: The frequency of and relationship between hospital readmissions and outcomes after revascularization for left main coronary artery disease (LMCAD) are unknown. OBJECTIVES: The purpose of this study was to study the incidence, predictors, and clinical impact of readmissions following percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for LMCAD. METHODS: In the EXCEL (XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial, 1,905 patients with LMCAD were randomized to PCI vs CABG. The cumulative incidence of readmissions was analyzed with multivariable Anderson-Gill and joint frailty models to account for recurrent events and the competing risk of death. The impact of readmission on subsequent mortality within 5-year follow-up was determined in a time-adjusted Cox proportional hazards model. RESULTS: Within 5 years, 1,868 readmissions occurred in 851 of 1,882 (45.2%) hospital survivors (2.2 ± 1.9 per patient with readmission[s], range 1-16), approximately one-half for cardiovascular causes and one-half for noncardiovascular causes (927 [49.6%] and 941 [50.4%], respectively). One or more readmissions occurred in 463 of 942 (48.6%) PCI patients vs 388 of 940 (41.8%) CABG patients (P = 0.003). After multivariable adjustment, PCI remained an independent predictor of readmission (adjusted HR: 1.22; 95% CI: 1.10-1.35; P < 0.0001), along with female sex, comorbidities, and the extent of CAD. Readmission was independently associated with subsequent all-cause death, with interaction testing indicating a higher risk after PCI than CABG (adjusted HR: 5.72; 95% CI: 3.42-9.55 vs adjusted HR: 2.72; 95% CI: 1.64-4.88, respectively; Pint = 0.03). CONCLUSIONS: In the EXCEL trial, readmissions during 5-year follow-up after revascularization for LMCAD were common and more frequent after PCI than CABG. Readmissions were associated with an increased risk of all-cause death, more so after PCI than with CABG.

One-month DAPT with ticagrelor and aspirin for patients undergoing coronary artery bypass grafting: rationale and design of the randomised, multicentre, double-blind, placebo-controlled ODIN trial.

The optimal antiplatelet strategy after coronary artery bypass graft (CABG) surgery in patients with chronic coronary syndromes (CCS) is unclear. Adding the P2Y12 inhibitor, ticagrelor, to low-dose aspirin for 1 year is associated with a reduction in graft failure, particularly saphenous vein grafts, at the expense of an increased risk of clinically important bleeding. As the risk of thrombotic graft failure and ischaemic events is highest early after CABG surgery, a better risk-to-benefit profile may be attained with short-term dual antiplatelet therapy followed by single antiplatelet therapy. The One Month Dual Antiplatelet Therapy With Ticagrelor in Coronary Artery Bypass Graft Patients (ODIN) trial is a prospective, randomised, double-blind, placebo-controlled, international, multicentre study of 700 subjects that will evaluate the effect of short-term dual antiplatelet therapy with ticagrelor plus low-dose aspirin after CABG in patients with CCS. Patients will be randomised 1:1 to ticagrelor 90 mg twice daily or matching placebo, in addition to aspirin 75-150 mg once daily for 1 month; after the first month, antiplatelet therapy will be continued with aspirin alone. The primary endpoint is a hierarchical composite of all-cause death, stroke, myocardial infarction, revascularisation and graft failure at 1 year. The key secondary endpoint is a hierarchical composite of all-cause death, stroke, myocardial infarction, Bleeding Academic Research Consortium (BARC) type 3 bleeding, revascularisation and graft failure at 1 year (net clinical benefit). ODIN will report whether the addition of ticagrelor to low-dose aspirin for 1 month after CABG reduces ischaemic events and provides a net clinical benefit in patients with CCS. (ClinicalTrials.gov: NCT05997693).

European Association of Cardio-Thoracic Surgery (EACTS) expert consensus statement on perioperative myocardial infarction after cardiac surgery.

Cardiac surgery may lead to myocardial damage and release of cardiac biomarkers through various mechanisms such as cardiac manipulation, systemic inflammation, myocardial hypoxia, cardioplegic arrest and ischaemia caused by coronary or graft occlusion. Defining perioperative myocardial infarction (PMI) after cardiac surgery presents challenges, and the association between the current PMI definitions and postoperative outcomes remains uncertain. To address these challenges, the European Association of Cardio-Thoracic Surgery (EACTS) facilitated collaboration among a multidisciplinary group to evaluate the existing evidence on the mechanisms, diagnosis and prognostic implications of PMI after cardiac surgery. The review found that the postoperative troponin value thresholds associated with an increased risk of mortality are markedly higher than those proposed by all the current definitions of PMI. Additionally, it was found that large postoperative increases in cardiac biomarkers are prognostically relevant even in absence of additional supportive signs of ischaemia. A new algorithm for PMI detection after cardiac surgery was also proposed, and a consensus was reached within the group that establishing a prognostically relevant definition of PMI is critically needed in the cardiovascular field and that PMI should be included in the primary composite outcome of coronary intervention trials.

Intraoperative Anemia Mediates Sex Disparity in Operative Mortality After Coronary Artery Bypass Grafting.

BACKGROUND: Women undergoing coronary artery bypass grafting (CABG) have higher operative mortality than men. OBJECTIVES: The purpose of this study was to evaluate the relationship between intraoperative anemia (nadir intraoperative hematocrit), CABG operative mortality, and sex. METHODS: This was a cohort study of 1,434,225 isolated primary CABG patients (344,357 women) from the Society of Thoracic Surgeons Adult Cardiac Surgery Database (2011-2022). The primary outcome was operative mortality. The attributable risk (AR) (the risk-adjusted strength of the association of female sex with CABG outcomes) for the primary outcome was calculated. Causal mediation analysis derived the total effect of female sex on operative mortality risk and the proportion of that effect mediated by intraoperative anemia. RESULTS: Women had lower median nadir intraoperative hematocrit (22.0% [Q1-Q3: 20.0%-25.0%] vs 27.0% [Q1-Q3: 24.0%-30.0%], standardized mean difference 97.0%) than men. Women had higher operative mortality than men (2.8% vs 1.7%; P < 0.001; adjusted OR: 1.36; 95% CI: 1.30-1.41). The AR of female sex for operative mortality was 1.21 (95% CI: 1.17-1.24). After adjusting for nadir intraoperative hematocrit, AR was reduced by 43% (1.12; 95% CI: 1.09-1.16). Intraoperative anemia mediated 38.5% of the increased mortality risk associated with female sex (95% CI: 32.3%-44.7%). Spline regression showed a stronger association between operative mortality and nadir intraoperative hematocrit at hematocrit values <22.0% (P < 0.001). CONCLUSIONS: The association of female sex with increased CABG operative mortality is mediated to a large extent by intraoperative anemia. Avoiding nadir intraoperative hematocrit values below 22.0% may reduce sex differences in CABG operative mortality.

Outcomes According to Coronary Revascularization Modality in the ISCHEMIA Trial.

BACKGROUND: In the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial, the risk of ischemic events was similar in patients with stable coronary artery disease treated with an invasive (INV) strategy of angiography and percutaneous coronary intervention (PCI) or surgical (coronary artery bypass grafting [CABG]) coronary revascularization and a conservative (CON) strategy of initial medical therapy. OBJECTIVES: The authors analyzed separately the outcomes of INV patients treated with PCI or CABG. METHODS: Patients without preceding primary outcome events were categorized as INV-PCI or INV-CABG from the time of revascularization. The ISCHEMIA primary outcome (composite of cardiovascular death, protocol-defined myocardial infarction or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest) was used. RESULTS: Among INV-CABG patients, primary outcome events occurred in 84 of 512 (16.4%) at a median follow-up of 2.85 years; 48 events (57.1%) occurred within 30 days after CABG, including 40 procedural MIs. Among INV-PCI patients, primary outcome events occurred in 147 of 1,500 (9.8%) at median follow-up of 2.94 years; 31 of which (21.1%) occurred within 30 days after PCI, including 24 procedural MIs. In comparison, 352 of 2,591 CON patients (13.6%) had primary outcome events at a median follow-up of 3.2 years, 22 of which (6.3%) occurred within 30 days of randomization. The adjusted primary outcome risks were higher after both CABG and PCI within 30 days (HR: 16.25 [95% CI: 11.44-23.07] and HR: 2.99 [95% CI: 1.97-4.53]) and lower thereafter (0.63 [95% CI: 0.44-0.89] and 0.66 [95% CI: 0.53-0.82]). CONCLUSIONS: In ISCHEMIA, early revascularization by PCI and CABG was associated with higher early risks and lower long-term risks of cardiovascular events compared with CON. The early risk was greatest after CABG, owing to protocol-defined procedural MIs.

Distal aortic biomechanics after transcatheter versus surgical aortic valve replacement: a hypothesis generating study.

BACKGROUND: Biomechanical effects of transcatheter (TAVR) versus surgical (SAVR) aortic valve interventions on the distal aorta have not been studied. This study utilized global circumferential strain (GCS) to assess post-procedural biomechanics changes in the descending aorta after TAVR versus SAVR. METHODS: Patients undergoing TAVR or SAVR for aortic stenosis were included. Transesophageal (TEE) and transthoracic (TTE) echocardiography short-axis images of the aorta were used to image the descending aorta immediately before and after interventions. Image analysis was performed with two-dimensional speckle tracking echocardiography and dedicated software. Delta GCS was calculated as: post-procedural GCS-pre-procedural GCS. Percentage delta GCS was calculated as: (delta GCS/pre-procedural GCS) × 100. RESULTS: Eighty patients, 40 TAVR (median age 81 y/o, 40% female) and 40 SAVR (median 72 y/o, 30% female) were included. The post-procedure GCS was significantly higher than the pre-procedural GCS in the TAVR (median 10.7 [interquartile range IQR 4.5, 14.6] vs. 17.0 [IQR 6.1, 20.9], p = 0.009) but not in the SAVR group (4.4 [IQR 3.3, 5.3] vs. 4.7 [IQR 3.9, 5.6], p = 0.3). The delta GCS and the percentage delta GCS were both significantly higher in the TAVR versus SAVR group (2.8% [IQR 1.4, 6] vs. 0.15% [IQR - 0.6, 1.5], p < 0.001; and 28.8% [IQR 14.6%, 64.6%] vs. 4.4% [IQR - 10.6%, 5.6%], p = 0.006). Results were consistent after multivariable adjustment for key clinical and hemodynamic characteristics. CONCLUSIONS: After TAVR, there was a significantly larger increase in GCS in the distal aorta compared to SAVR. This may impact descending aortic remodeling and long-term risk of aortic events.

The Effect of Posterior Pericardiotomy on the Incidence of Atrial Fibrillation After Cardiac Surgery-Extended Follow-Up study (PALACS-EF): rationale and design.

Aims: Postoperative atrial fibrillation (POAF) is the most common complication of cardiac surgery and has been associated with increased postoperative morbidity and hospital costs. The Posterior left pericardiotomy for the prevention of AtriaL fibrillation After Cardiac Surgery (PALACS) trial found that posterior pericardiotomy significantly reduced the incidence of POAF (17% vs. 32%, P < 0.001). We present the protocol for The Effect of Posterior Pericardiotomy on the Incidence of Atrial Fibrillation After Cardiac Surgery-Extended Follow-Up study (PALACS-EF): a prospective, extended follow-up of the original PALACS trial. The aim of PALACS-EF is to gain more data regarding the effect of posterior pericardiotomy on postdischarge clinical outcomes. The primary outcome is the time to the first occurrence of the composite of all-cause mortality or hospital cardiovascular readmission. The key secondary outcome is the time to the first occurrence of the composite of all-cause mortality and all-cause hospital readmission. Hospital readmission, myocardial infarction, stroke, transient ischaemic attack, heart failure, systemic embolism, or new arrhythmias with onset since 30-day follow-up will also be recorded. Methods and results: All 420 patients enrolled in the PALACS trial will be included; extended follow-up will be conducted via telephone by blinded research personnel utilizing a standardized script to ensure uniformity and completeness of follow-up. If an event has occurred, documentation will be obtained, and an independent adjudication committee blinded to group assignment will adjudicate outcome events. Results will be reported when a median follow-up of 5 years is achieved. Conclusion: PALACS-EF will provide data to answer the question of whether posterior pericardiotomy improves postdischarge outcomes in patients undergoing cardiac surgery, and it will provide information on the relationship between POAF and adverse postdischarge outcomes including mortality, hospitalization, heart failure, and stroke. Registration: PALACS: NCT02875405, PALACS-EF: NCT05903222.

Tricuspid Valve Academic Research Consortium Definitions for Tricuspid Regurgitation and Trial Endpoints.

Interest in the pathophysiology, etiology, management, and outcomes of patients with tricuspid regurgitation (TR) has grown in the wake of multiple natural history studies showing progressively worse outcomes associated with increasing TR severity, even after adjusting for multiple comorbidities. Historically, isolated tricuspid valve surgery has been associated with high in-hospital mortality rates, leading to the development of transcatheter treatment options. The aim of this first Tricuspid Valve Academic Research Consortium document is to standardize definitions of disease etiology and severity, as well as endpoints for trials that aim to address the gaps in our knowledge related to identification and management of patients with TR. Standardizing endpoints for trials should provide consistency and enable meaningful comparisons between clinical trials. A second Tricuspid Valve Academic Research Consortium document will focus on further defining trial endpoints and will discuss trial design options.

Tricuspid Valve Academic Research Consortium Definitions for Tricuspid Regurgitation and Trial Endpoints.

Interest in the pathophysiology, etiology, management, and outcomes of patients with tricuspid regurgitation (TR) has grown in the wake of multiple natural history studies showing progressively worse outcomes associated with increasing TR severity, even after adjusting for multiple comorbidities. Historically, isolated tricuspid valve surgery has been associated with high in-hospital mortality rates, leading to the development of transcatheter treatment options. The aim of this first Tricuspid Valve Academic Research Consortium document is to standardize definitions of disease etiology and severity, as well as endpoints for trials that aim to address the gaps in our knowledge related to identification and management of patients with TR. Standardizing endpoints for trials should provide consistency and enable meaningful comparisons between clinical trials. A second Tricuspid Valve Academic Research Consortium document will focus on further defining trial endpoints and will discuss trial design options.

Tricuspid Valve Academic Research Consortium Definitions for Tricuspid Regurgitation and Trial Endpoints.

Interest in the pathophysiology, etiology, management, and outcomes of patients with tricuspid regurgitation (TR) has grown in the wake of multiple natural history studies showing progressively worse outcomes associated with increasing TR severity, even after adjusting for multiple comorbidities. Historically, isolated tricuspid valve surgery has been associated with high in-hospital mortality rates, leading to the development of transcatheter treatment options. The aim of this first Tricuspid Valve Academic Research Consortium document is to standardize definitions of disease etiology and severity, as well as endpoints for trials that aim to address the gaps in our knowledge related to identification and management of patients with TR. Standardizing endpoints for trials should provide consistency and enable meaningful comparisons between clinical trials. A second Tricuspid Valve Academic Research Consortium document will focus on further defining trial endpoints and will discuss trial design options.

Antiplatelet therapy around CABG: the latest evidence.

PURPOSE OF REVIEW: The optimal antiplatelet strategy in patients after coronary artery bypass graft (CABG) surgery is unclear. We review the evidence on the efficacy and safety of DAPT after CABG and discuss potential novel antiplatelet strategies that reduce the risk of bleeding without loss of efficacy. RECENT FINDINGS: Adding the potent P2Y12 inhibitor ticagrelor to aspirin for 1 year after CABG is associated with a reduction in the risk of vein graft failure, at the expense of an increased risk of clinically important bleeding. Ticagrelor monotherapy is not associated with better efficacy than aspirin alone, but is not associated with increased bleeding risk. SUMMARY: Dual antiplatelet therapy (DAPT) is recommended after acute coronary syndrome events, but aspirin as single antiplatelet therapy remains the cornerstone of antithrombotic therapy in stable ischemic heart disease because of a lack of solid evidence on the benefit of DAPT on clinical outcomes. Shorter duration DAPT, based on the pathophysiology of vein graft failure, may be a promising strategy that requires testing in adequately powered randomized trials.

Sex Differences in pLVAD-Assisted High-Risk Percutaneous Coronary Intervention: Insights From the PROTECT III Study.

BACKGROUND: Prior studies have found that female patients have worse outcomes following high-risk percutaneous coronary intervention (HRPCI). OBJECTIVES: The authors sought to evaluate sex-based differences in patient and procedural characteristics, clinical outcomes, and safety of Impella-supported HRPCI in the PROTECT III study. METHODS: We evaluated sex-based differences in the PROTECT III study; a prospective, multicenter, observational study of patients undergoing Impella-supported HRPCI. The primary outcome was 90-day major adverse cardiac and cerebrovascular events (MACCE)-the composite of all-cause death, myocardial infarction, stroke/transient ischemic attack, and repeat revascularization. RESULTS: From March 2017 to March 2020, 1,237 patients (27% female) were enrolled. Female patients were older, more often Black, more often anemic, and had more prior strokes and worse renal function, but higher ejection fractions compared to male patients. Preprocedural SYNTAX score was similar between sexes (28.0 ± 12.3). Female patients were more likely to present with acute myocardial infarction (40.7% vs 33.2%; P = 0.02) and more often had femoral access used for PCI and nonfemoral access used for Impella device implantation. Female patients had higher rates of immediate PCI-related coronary complications (4.2% vs 2.1%; P = 0.004) and a greater drop in SYNTAX score post-procedure (-22.6 vs -21.0; P = 0.04). There were no sex differences in 90-day MACCE, vascular complications requiring surgery, major bleeding, or acute limb ischemia. After adjustment using propensity matching and multivariable regression, immediate PCI-related complications was the only safety or clinical outcome that was significantly different by sex. CONCLUSIONS: In this study, rates of 90-day MACCE compared favorably to prior cohorts of HRPCI patients and there was no significant sex differences. (The PROTECT III Study is a substudy of The Global cVAD Study [cVAD]; NCT04136392).

Graft Failure After Coronary Artery Bypass Grafting and Its Association With Patient Characteristics and Clinical Events: A Pooled Individual Patient Data Analysis of Clinical Trials With Imaging Follow-Up.

BACKGROUND: Graft patency is the postulated mechanism for the benefits of coronary artery bypass grafting (CABG). However, systematic graft imaging assessment after CABG is rare, and there is a lack of contemporary data on the factors associated with graft failure and on the association between graft failure and clinical events after CABG. METHODS: We pooled individual patient data from randomized clinical trials with systematic CABG graft imaging to assess the incidence of graft failure and its association with clinical risk factors. The primary outcome was the composite of myocardial infarction or repeat revascularization occurring after CABG and before imaging. A 2-stage meta-analytic approach was used to evaluate the association between graft failure and the primary outcome. We also assessed the association between graft failure and myocardial infarction, repeat revascularization, or all-cause death occurring after imaging. RESULTS: Seven trials were included comprising 4413 patients (mean age, 64.4±9.1 years; 777 [17.6%] women; 3636 [82.4%] men) and 13 163 grafts (8740 saphenous vein grafts and 4423 arterial grafts). The median time to imaging was 1.02 years (interquartile range [IQR], 1.00-1.03). Graft failure occurred in 1487 (33.7%) patients and in 2190 (16.6%) grafts. Age (adjusted odds ratio [aOR], 1.08 [per 10-year increment] [95% CI, 1.01-1.15]; P=0.03), female sex (aOR, 1.27 [95% CI, 1.08-1.50]; P=0.004), and smoking (aOR, 1.20 [95% CI, 1.04-1.38]; P=0.01) were independently associated with graft failure, whereas statins were associated with a protective effect (aOR, 0.74 [95% CI, 0.63-0.88]; P<0.001). Graft failure was associated with an increased risk of myocardial infarction or repeat revascularization occurring between CABG and imaging assessment (8.0% in patients with graft failure versus 1.7% in patients without graft failure; aOR, 3.98 [95% CI, 3.54-4.47]; P<0.001). Graft failure was also associated with an increased risk of myocardial infarction or repeat revascularization occurring after imaging (7.8% versus 2.0%; aOR, 2.59 [95% CI, 1.86-3.62]; P<0.001). All-cause death after imaging occurred more frequently in patients with graft failure compared with patients without graft failure (11.0% versus 2.1%; aOR, 2.79 [95% CI, 2.01-3.89]; P<0.001). CONCLUSIONS: In contemporary practice, graft failure remains common among patients undergoing CABG and is strongly associated with adverse cardiac events.

Myeloperoxidase Inhibition Reverses Biomarker Profiles Associated With Clinical Outcomes in HFpEF.

BACKGROUND: Systemic microvascular dysfunction and inflammation are postulated to play a pathophysiologic role in heart failure with preserved ejection fraction (HFpEF). OBJECTIVES: This study aimed to identify biomarker profiles associated with clinical outcomes in HFpEF and investigate how inhibition of the neutrophil-derived reactive oxygen species-producing enzyme, myeloperoxidase, affects these biomarkers. METHODS: Using supervised principal component analyses, the investigators assessed the associations between baseline plasma proteomic Olink biomarkers and clinical outcomes in 3 independent observational HFpEF cohorts (n = 86, n = 216, and n = 242). These profiles were then compared with the biomarker profiles discriminating patients treated with active drug vs placebo in SATELLITE (Safety and Tolerability Study of AZD4831 in Patients With Heart Failure), a double-blind randomized 3-month trial evaluating safety and tolerability of the myeloperoxidase inhibitor AZD4831 in HFpEF (n = 41). Pathophysiological pathways were inferred from the biomarker profiles by interrogation of the Ingenuity Knowledge Database. RESULTS: TNF-R1, TRAIL-R2, GDF15, U-PAR, and ADM were the top individual biomarkers associated with heart failure hospitalization or death, and FABP4, HGF, RARRES2, CSTB, and FGF23 were associated with lower functional capacity and poorer quality of life. AZD4831 downregulated many markers (most significantly CDCP1, PRELP, CX3CL1, LIFR, VSIG2). There was remarkable consistency among pathways associated with clinical outcomes in the observational HFpEF cohorts, the top canonical pathways being associated with tumor microenvironments, wound healing signaling, and cardiac hypertrophy signaling. These pathways were predicted to be downregulated in AZD4831 relative to placebo-treated patients. CONCLUSIONS: Biomarker pathways that were most strongly associated with clinical outcomes were also the ones reduced by AZD4831. These results support the further investigation of myeloperoxidase inhibition in HFpEF.

Rationale and design of BROKEN-SWEDEHEART: a registry-based, randomized, parallel, open-label multicenter trial to test pharmacological treatments for broken heart (takotsubo) syndrome.

BACKGROUND: Takotsubo syndrome (TS) is a life-threatening acute heart failure syndrome without any evidence-based treatment options. No treatment for TS has been examined in a randomized trial. STUDY DESIGN AND OBJECTIVES: BROKEN-SWEDEHEART is a multicenter, randomized, open-label, registry-based 2 × 2 factorial clinical trial in patients with TS designed to test whether treatment with adenosine and dipyridamole accelerates cardiac recovery and improves clinical outcomes compared to standard care (study 1); and apixaban reduces the risk of thromboembolic events compared to no treatment with antithrombotic drugs (study 2). The trial will enroll 1,000 patients. Study 1 (adenosine hypothesis) will evaluate 2 coprimary end points: (1) wall motion score index at 48 to 96 hours (evaluated in the first 200 patients); and (2) the composite of death, cardiac arrest, need for mechanical assist device or heart failure hospitalization within 30 days or left ventricular ejection fraction <50% at 48 to 96 hours (evaluated in 1,000 patients). The primary end point in study 2 (apixaban hypothesis) is the composite of death or thromboembolic events within 30 days or the presence of intraventricular thrombus on echocardiography at 48 to 96 hours. CONCLUSIONS: BROKEN-SWEDEHEART will be the first prospective randomized multicenter trial in patients with TS. It is designed as 2 parallel studies to evaluate whether adenosine accelerates cardiac recovery and improves cardiac function in the acute phase and the efficacy of anticoagulation therapy for preventing thromboembolic complications in TS. If either of its component studies is successful, the trial will provide the first evidence-based treatment recommendation in TS. CLINICAL TRIALS IDENTIFIER: The trial has been approved by the Swedish Medicinal Product Agency and the Swedish Ethical Board and is registered at ClinicalTrials.gov (NCT04666454).

Association of Dual Antiplatelet Therapy With Ticagrelor With Vein Graft Failure After Coronary Artery Bypass Graft Surgery: A Systematic Review and Meta-analysis.

Importance: The role of ticagrelor with or without aspirin after coronary artery bypass graft surgery remains unclear. Objective: To compare the risks of vein graft failure and bleeding associated with ticagrelor dual antiplatelet therapy (DAPT) or ticagrelor monotherapy vs aspirin among patients undergoing coronary artery bypass graft surgery. Data Sources: MEDLINE, Embase, and Cochrane Library databases from inception to June 1, 2022, without language restriction. Study Selection: Randomized clinical trials (RCTs) comparing the effects of ticagrelor DAPT or ticagrelor monotherapy vs aspirin on saphenous vein graft failure. Data Extraction and Synthesis: Individual patient data provided by each trial were synthesized into a combined data set for independent analysis. Multilevel logistic regression models were used. Main Outcomes and Measures: The primary analysis assessed the incidence of saphenous vein graft failure per graft (primary outcome) in RCTs comparing ticagrelor DAPT with aspirin. Secondary outcomes were saphenous vein graft failure per patient and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding events. A supplementary analysis included RCTs comparing ticagrelor monotherapy with aspirin. Results: A total of 4 RCTs were included in the meta-analysis, involving 1316 patients and 1668 saphenous vein grafts. Of the 871 patients in the primary analysis, 435 received ticagrelor DAPT (median age, 67 years [IQR, 60-72 years]; 65 women [14.9%]; 370 men [85.1%]) and 436 received aspirin (median age, 66 years [IQR, 61-73 years]; 63 women [14.5%]; 373 men [85.5%]). Ticagrelor DAPT was associated with a significantly lower incidence of saphenous vein graft failure (11.2%) per graft than was aspirin (20%; difference, -8.7% [95% CI, -13.5% to -3.9%]; OR, 0.51 [95% CI, 0.35 to 0.74]; P < .001) and was associated with a significantly lower incidence of saphenous vein graft failure per patient (13.2% vs 23.0%, difference, -9.7% [95% CI, -14.9% to -4.4%]; OR, 0.51 [95% CI, 0.35 to 0.74]; P < .001). Ticagrelor DAPT (22.1%) was associated with a significantly higher incidence of BARC type 2, 3, or 5 bleeding events than was aspirin (8.7%; difference, 13.3% [95% CI, 8.6% to 18.0%]; OR, 2.98 [95% CI, 1.99 to 4.47]; P < .001), but not BARC type 3 or 5 bleeding events (1.8% vs 1.8%, difference, 0% [95% CI, -1.8% to 1.8%]; OR, 1.00 [95% CI, 0.37 to 2.69]; P = .99). Compared with aspirin, ticagrelor monotherapy was not significantly associated with saphenous vein graft failure (19.3% vs 21.7%, difference, -2.6% [95% CI, -9.1% to 3.9%]; OR, 0.86 [95% CI, 0.58 to 1.27]; P = .44) or BARC type 2, 3, or 5 bleeding events (8.9% vs 7.3%, difference, 1.7% [95% CI, -2.8% to 6.1%]; OR, 1.25 [95% CI, 0.69 to 2.29]; P = .46). Conclusions and Relevance: Among patients undergoing coronary artery bypass graft surgery, adding ticagrelor to aspirin was associated with a significantly decreased risk of vein graft failure. However, this was accompanied by a significantly increased risk of clinically important bleeding.