Search

Abstract Aims Interatrial shunts are under evaluation as a treatment for heart failure (HF); however, their in vivo flow performance has not been quantitatively studied. We aimed to investigate the fluid dynamics properties of the 0.51 cm orifice diameter Ventura shunt and assess its lumen integrity with serial transesophageal echocardiography (TEE). Methods and results Computational fluid dynamics (CFD) and bench flow tests were used to establish the flow‐pressure relationship of the shunt. Open‐label patients from the RELIEVE‐HF trial underwent TEE at shunt implant and at 6 and 12 month follow‐up. Shunt effective diameter (Deff) was derived from the vena contracta, and flow was determined by the continuity equation. CFD and bench studies independently validated that the shunt's discharge coefficient was 0.88 to 0.89. The device was successfully implanted in all 97 enrolled patients; mean age was 70 ± 11 years, 97% were NYHA class III, and 51% had LVEF ≤40%. Patency was confirmed in all instances, except for one stenotic shunt at 6 months. Deff remained unchanged from baseline at 12 months (0.47 ± 0.01 cm, P = 0.376), as did the trans‐shunt mean pressure gradient (5.1 ± 3.9 mmHg, P = 0.316) and flow (1137 ± 463 mL/min, P = 0.384). TEE measured flow versus pressure closely correlated (R2 ≥ 0.98) with a fluid dynamics model. At 12 months, the pulmonary/systemic flow Qp/Qs ratio was 1.22 ± 0.12. Conclusions When implanted in patients with advanced HF, this small interatrial shunt demonstrated predictable and durable patency and performance.

Abstract Background Conflicting results comparing bivalirudin versus heparin anticoagulation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), in part due to the confounding effect of glycoprotein IIb/IIIa inhibitors (GPI). The aim of the study was to compare the safety and effectiveness of bivalirudin plus a post-PCI high-dose infusion vs heparin with or without bail-out GPI use. Methods We conducted a pre-specified subgroup analysis from the BRIGHT-4 trial that randomized 6016 STEMI patients who underwent primary PCI to receive either bivalirudin plus a post-PCI high-dose infusion for 2–4 h or heparin monotherapy. GPI use was only reserved as bail-out therapy for procedural thrombotic complications. The primary outcome was a composite of all-cause death or Bleeding Academic Research Consortium (BARC) types 3–5 bleeding at 30 days. Results A total of 5250 (87.4%) patients received treatment without GPI while 758 (12.6%) received bail-out GPI. Bail-out GPI use was associated with an increased risk of the primary outcome compared to non-GPI use (5.28% vs. 3.41%; adjusted hazard ratio (aHR), 1.62; 95% confidence interval (CI), 1.13–2.33; P = 0.009) and all-cause death (5.01% vs. 3.12%; aHR, 1.74; 95% CI, 1.20–2.52; P = 0.004) but not in the risk of BARC types 3–5 bleeding (0.53% vs. 0.48%; aHR, 0.90; 95% CI, 0.31–2.66; P = 0.85). Among patients without GPI use, bivalirudin was associated with lower rates of the primary outcome (2.63% vs. 4.21%; aHR, 0.55; 95% CI, 0.39–0.77; P = 0.0005), all-cause death (2.52% vs. 3.74%; aHR, 0.58; 95% CI, 0.41–0.83; P = 0.003), and BARC types 3–5 bleeding (0.15% vs. 0.81%; aHR, 0.19; 95% CI, 0.06–0.57; P = 0.003) compared with heparin. However, among patients requiring bail-out GPI, there were no significant differences observed in the rates of the primary outcome (5.76% vs. 4.87%; aHR, 0.77; 95% CI, 0.36–1.66; P = 0.50; P interaction = 0.07) or its individual components between bivalirudin and heparin groups. Conclusions Bivalirudin plus a post-PCI high-dose infusion was associated with significantly reduced 30-day composite rate of all-cause death or BARC types 3–5 bleeding compared with heparin monotherapy in STEMI patients undergoing primary PCI without GPI use. However, these benefits might be less pronounced in patients requiring bail-out GPI due to thrombotic complications during primary PCI. Trial registration ClinicalTrials.gov NCT03822975.

Background The BIONICS (BioNIR Ridaforolimus‐Eluting Coronary Stent System in Coronary Stenosis) and the NIREUS (BioNIR Ridaforolimus Eluting Coronary Stent System [BioNIR] European Angiography Study) randomized clinical trials showed noninferiority of the ridaforolimus‐eluting stent (RES) compared with the zotarolimus‐eluting stent (ZES) with respect to 1‐year target‐lesion failure and 6‐month angiographic late lumen loss. We aimed to evaluate clinical outcomes between treatment groups over a 5‐year follow‐up. Methods and Results Patient‐level data from the BIONICS (n=1919) and NIREUS (n=302) were pooled, comparing the outcomes of patients implanted with RES and ZES. The primary end point was the 5‐year rate of target‐lesion failure. A total of 2221 patients (63.2±10.3 years, 79.7% men) undergoing percutaneous coronary intervention with RES (n=1159) or ZES (n=1062) were included. Most clinical and angiographic characteristics were similar between groups. At 5 years, the primary end point of target‐lesion failure was similar between treatment groups (12.2% RES versus 11.3% ZES, P=0.52). Rates of TLR (7.6% RES versus 6.8% ZES, P=0.42) target‐vessel–related myocardial infarction (4.8% RES versus 4.9% ZES, P=0.95) and stent thrombosis (0.9% RES versus 0.9% ZES, P=0.87) also did not differ between groups. Target‐vessel revascularization and cardiac death were higher among the RES group (12.3% versus 9.5% P=0.037, and 3.6% versus 2.2% P=0.042, respectively). However, after correction for baseline characteristics, there was no significant difference in cardiac death between groups. Conclusions In a pooled analysis of 2 randomized trials, 5‐year clinical outcomes were similar between patients undergoing percutaneous coronary intervention with RES and ZES. These results support the long‐term safety and efficacy of RES for the treatment of patients with coronary artery disease.

Background The extent to which infarct artery impacts the extent of myocardial injury and outcomes in patients with ST‐segment–elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention is uncertain. Methods and Results We performed a pooled analysis using individual patient data from 7 randomized STEMI trials in which myocardial injury within 30 days after primary percutaneous coronary intervention was assessed in 1774 patients by cardiac magnetic resonance (n=1318) or technetium‐99m sestamibi single‐photon emission computed tomography (n=456). Clinical follow‐up was performed at a median duration of 351 days (interquartile range, 184–368 days). Infarct size and outcomes were assessed in anterior (infarct vessel=left anterior descending) versus nonanterior (non–left anterior descending) STEMI. Median infarct size (percentage left ventricular myocardial mass) was larger in patients with anterior compared with nonanterior STEMI (19.7% [interquartile range, 9.4%–31.7%] versus 12.6% [interquartile range, 5.1%–20.5%]; P

Background Patients may prefer percutaneous coronary intervention (PCI) over coronary artery bypass graft (CABG) surgery, despite heart team recommendations. The outcomes in such patients have not been examined. We sought to examine the results of PCI in patients who were recommended for but declined CABG. Methods and Results Consecutive patients with stable ischemic heart disease and unprotected left main or 3‐vessel disease or Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery score >22 who underwent PCI after heart team review between 2013 and 2020 were included. Patients were categorized into 3 groups according to heart team recommendations on the basis of appropriate use criteria: (1) PCI‐recommended; (2) CABG‐eligible but refused CABG (CABG‐refusal); and (3) CABG‐ineligible. The primary end point was the composite of death, myocardial infarction, or stroke at 1 year. The study included 3687 patients undergoing PCI (PCI‐recommended, n=1718 [46.6%]), CABG‐refusal (n=1595 [43.3%]), and CABG‐ineligible (n=374 [10.1%]). Clinical and procedural risk increased across the 3 groups, with the highest comorbidity burden in CABG‐ineligible patients. Composite events within 1 year after PCI occurred in 55 (4.1%), 91 (7.0%), and 41 (14.8%) of patients in the PCI‐recommended, CABG‐refusal, and CABG‐ineligible groups, respectively. After multivariable adjustment, the risk of the primary composite outcome was significantly higher in the CABG‐refusal (hazard ratio [HR], 1.67 [95% CI, 1.08–3.56]; P=0.02) and CABG‐ineligible patients (HR, 3.26 [95% CI, 1.28–3.65]; P=0.004) groups compared with the reference PCI‐recommended group, driven by increased death and stroke. Conclusions Cardiovascular event rates after PCI were significantly higher in patients with multivessel disease who declined or were ineligible for CABG. Our findings provide real‐world data to inform shared decision‐making discussions.

IntroductionPrompt reperfusion of coronary artery after acute myocardial infarction (AMI) is crucial for minimizing heart injury. The myocardium, however, may experience additional injury due to the flow restoration itself (reperfusion injury, RI). The purpose of this study was to demonstrate that short preconditioning (10 min) with selective autoretroperfusion (SARP) ameliorates RI, based on a washout hypothesis.MethodsAMI was induced in 23 pigs (3 groups) by occluding the left anterior descending (LAD) artery. In SARP-b (SARP balloon inflated) and SARP-nb (SARP balloon deflated) groups, arterial blood was retroperfused for 10 min via the great cardiac vein before releasing the arterial occlusion. A mathematical model of coronary circulation was used to simulate the SARP process and evaluate the potential washout effect.ResultsSARP restored left ventricular function during LAD occlusion. Ejection fraction in the SARP-b group returned to baseline levels, compared to SARP-nb and control groups. Infarct area was significantly larger in the control group than in the SARP-b and SARP-nb groups. End-systolic wall thickness was preserved in the SARP-b compared to the SARP-nb and control groups. Analyte values (pH, lactate, glucose, and others), measured every 2 min during retroperfusion, suggest a “washout” effect as one important mechanism of action of SARP in reducing infarct size. With SARP, the values progressively approached baseline levels. The mathematical model also confirmed a possible washout effect of tracers.DiscussionRI can be ameliorated by delaying restoration of arterial flow for a brief period of time while pretreating the infarction with SARP to restore homeostasis via a washout mechanism.

Objective: We performed a post hoc analysis of the Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial to determine the effect an on-versus off-pump strategy had on outcomes when compared with percutaneous coronary intervention. Methods: All randomized patients in EXCEL (n = 1905) were included. The outcomes of interest were the primary end point composite of death from any cause, stroke, or myocardial infarction; the composite study end point or ischemia-driven revascularization; and the rate of death from any cause at 5 years. Event rates were based on Kaplan–Meier estimates in time-to-first-event analyses. Results: Propensity matching resulted in groups of 1142 patients (571 each) for on-pump coronary artery bypass grafting versus percutaneous coronary intervention and 472 patients (236 each) for off-pump coronary artery bypass grafting versus percutaneous coronary intervention. In the on-pump coronary artery bypass grafting versus percutaneous coronary intervention matched groups, the composite end point was similar (18.0% vs 22.1%, P = .19) and the composite end point or ischemia-driven revascularization (23.3% vs 31.0%, P = .01) was lower, and mortality (7.6% vs 11.8%, P = .025) was lower in the on-pump coronary artery bypass grafting group at 5 years. In the off-pump coronary artery bypass grafting versus percutaneous coronary intervention matched groups, the composite end point (19.4% vs 22.2%, P = .47), composite end point or ischemia-driven revascularization (25.9% vs 34.2%, P = .07), and mortality (12.5% vs 14.2%, P = .59) were similar at 5 years. Conclusions: In the EXCEL trial, on-pump coronary artery bypass grafting was associated with a decreased 5-year rate of the composite outcome of death, stroke, myocardial infarction, or ischemia-driven revascularization, and decreased mortality when compared with percutaneous coronary intervention, whereas outcomes of off-pump coronary artery bypass grafting were similar to percutaneous coronary intervention.

Background Women with chronic coronary disease are generally older than men and have more comorbidities but less atherosclerosis. We explored sex differences in revascularization, guideline‐directed medical therapy, and outcomes among patients with chronic coronary disease with ischemia on stress testing, with and without invasive management. Methods and Results The ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial randomized patients with moderate or severe ischemia to invasive management with angiography, revascularization, and guideline‐directed medical therapy, or initial conservative management with guideline‐directed medical therapy alone. We evaluated the primary outcome (cardiovascular death, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest) and other end points, by sex, in 1168 (22.6%) women and 4011 (77.4%) men. Invasive group catheterization rates were similar, with less revascularization among women (73.4% of invasive‐assigned women revascularized versus 81.2% of invasive‐assigned men; P

Background Differences in quality of life (QoL) after coronary artery bypass grafting (CABG) compared with percutaneous coronary intervention (PCI) are not well characterized. We aimed to compare the short‐ and long‐term effects of CABG versus PCI on QoL. Methods and Results We performed a systematic review and meta‐analysis of randomized controlled trials comparing CABG versus PCI using the Seattle Angina Questionnaire (SAQ)‐Angina Frequency, SAQ‐QoL, SAQ‐Physical Limitations, EuroQoL‐5D, and Short‐Form Questionnaire. We calculated mean changes within each group from baseline to 1, 6, 12, and 36 to 60 months (latest follow‐up) and the weighted mean differences between groups using inverse‐variance methods. A total of 10 760 patients were enrolled in 5 trials. From baseline to 12 months and 36 to 60 months, the mean change in SAQ‐Angina Frequency was >22 points (95% CI, 21.0–25.6) after both PCI and CABG. The mean difference in SAQ‐Angina Frequency was similar between procedures at 1 month and at 36 to 60 months but favored CABG at 12 months (1.97 [95% CI, 0.68–3.26]). SAQ‐QoL favored PCI at 1 month (−2.92 [95% CI, −4.66 to −1.18]) and CABG at 6 (2.50 [95% CI, 1.02–3.97]), 12 (3.30 [95% CI, 1.78–4.82]), and 36 to 60 months (3.17 [95% CI, 0.54 5.80). SAQ‐Physical Limitations (−12.61 [95% CI, −16.16 to −9.06]) and EuroQoL‐5D (−0.07 [95% CI, −0.08 to −0.07) favored PCI at 1 month. Short‐Form Questionnaire‐Physical Component favored CABG at 12 months (1.18 [95% CI, 0.46–1.90]). Conclusions Both PCI and CABG improved long‐term disease‐specific and generic QoL.

Intravenous anticoagulant therapy is critical to prevent ischemic events without increasing the risk of bleeding in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Heparin and bivalirudin are the most commonly used adjunctive anticoagulant agents during PPCI. However, the superiority of the 2 most optimal regimens with these agents in patients undergoing PPCI remains controversial. The BivaliRudin with prolonged high-dose Infusion durinG PPCI versus Heparin Trial 4 (BRIGHT-4) is a large-scale, prospective, multicenter, active-control, parallel-group, open-label, randomized trial designed to test whether bivalirudin with a post-PCI high-dose infusion is superior to heparin monotherapy in STEMI patients undergoing PPCI. A total of 6000 patients will be enrolled and randomly assigned to receive bivalirudin or heparin in a 1:1 ratio. Patients allocated to the bivalirudin group will be treated with a high-dose bivalirudin infusion (1.75 mg/(kg·h)) after PCI for 2 to 4 hours. In the heparin group, the use of glycoprotein IIb/IIIa inhibitors will be reserved for the development of procedural thrombotic complications. The efficacy and safety of bivalirudin will be evaluated at 30 days, 6 months, and 12 months after the randomization. The primary endpoint is a composite of all-cause death or Bleeding Academic Research Consortium (BARC) types 3 to 5 bleeding at 30 days after randomization. The BRIGHT-4 study protocol has received approval from the ethics committee of General Hospital of Northern Theater Command (Shenyang, China). The procedures set out in this protocol are in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice guidelines. The results will be published following the Consolidated Standards of Reporting Trials statement in a peer-reviewed scientific journal (Trial registration number: NCT03822975).

Background Left ventricular (LV) global longitudinal strain (GLS) provides incremental prognostic information over LV ejection fraction in patients with heart failure (HF) and secondary mitral regurgitation. We examined the prognostic impact of LV GLS improvement in this population. Methods and Results The COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial randomized symptomatic patients with HF with severe (3+/4+) mitral regurgitation to transcatheter edge‐to‐edge repair with the MitraClip device plus maximally tolerated guideline‐directed medical therapy (GDMT) versus GDMT alone. LV GLS was measured at baseline and 6‐month follow‐up. The relationship between the improvement in LV GLS from baseline to 6 months and the composite of all‐cause death or HF hospitalization between 6‐ and 24‐month follow‐up were assessed. Among 383 patients, 174 (45.4%) had improved LV GLS at 6‐month follow‐up (83/195 [42.6%] with transcatheter edge‐to‐edge repair+GDMT and 91/188 [48.4%] with GDMT alone; P=0.25). Improvement in LV GLS was strongly associated with reduced death or HF hospitalization between 6 and 24 months (P

Background The incidence and implications of worsening renal function (WRF) after mitral valve transcatheter edge‐to‐edge repair (TEER) in patients with heart failure (HF) are unknown. Therefore, the aim of this study was to determine the proportion of patients with HF and secondary mitral regurgitation who develop persistent WRF within 30 days following TEER, and whether this development portends a worse prognosis. Methods and Results In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial, 614 patients with HF and severe secondary mitral regurgitation were randomized to TEER with the MitraClip plus guideline‐directed medical therapy (GDMT) versus GDMT alone. WRF was defined as serum creatinine increase ≥1.5× or ≥0.3 mg/dL from baseline persisting to day 30 or requiring renal replacement therapy. All‐cause death and HF hospitalization rates between 30 days and 2 years were compared in patients with and without WRF. WRF at 30 days was present in 11.3% of patients (9.7% in the TEER plus GDMT group and 13.1% in the GDMT alone group; P=0.23). WRF was associated with all‐cause death (hazard ratio [HR], 1.98 [95% CI, 1.3–3.03]; P=0.001) but not HF hospitalization (HR, 1.47 [ 95% CI, 0.97–2.24]; P=0.07) between 30 days and 2 years. Compared with GDMT alone, TEER reduced both death and HF hospitalization consistently in patients with and without WRF (Pinteraction=0.53 and 0.57, respectively). Conclusions Among patients with HF and severe secondary mitral regurgitation, the incidence of WRF at 30 days was not increased after TEER compared with GDMT alone. WRF was associated with greater 2‐year mortality but did not attenuate the treatment benefits of TEER in reducing death and HF hospitalization compared with GDMT alone. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01626079.

Background Peripheral artery disease (PAD) and heart failure (HF) often coexist. Whether PAD influences outcomes of transcatheter mitral valve repair (TMVr) in patients with HF and severe secondary mitral regurgitation is unknown. The objectives are to assess the impact of PAD on outcomes of TMVr plus guideline‐directed medical therapy (GDMT) versus GDMT alone in patients with HF and secondary mitral regurgitation. Methods and Results The COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) randomized patients with HF with ≥moderate‐to‐severe secondary mitral regurgitation to TMVr with MitraClip implant plus GDMT versus GDMT alone. We evaluated the relationship between PAD and 2‐year outcomes in the COAPT trial and examined whether PAD modified the benefits of TMVr. Among 614 patients enrolled, 109 (17.8%) had PAD. By multivariable analysis, PAD was independently associated with 2‐year mortality (adjusted hazard ratio [adjHR], 1.51 [95% CI, 1.07–2.15]) but not HF hospitalizations. Compared with GDMT alone, TMVr reduced the 2‐year risk of death in patients without PAD (adjHR, 0.42 [95% CI, 0.30–0.60]) but not those with PAD (adjHR, 1.27 [95% CI, 0.72–2.27]; Pinteraction=0.001). In contrast, TMVr reduced HF hospitalizations consistently in patients with (adjHR, 0.65 [95% CI, 0.35–1.23]) and without (adjHR, 0.42 [95% CI, 0.31–0.57]) PAD (Pinteraction=0.22). Improvements in health status and exercise capacity at 2 years with TMVr compared with GDMT alone were similar in degree, irrespective of PAD status (Pinteraction=0.76 and 0.64, respectively). Conclusions In patients with HF and severe secondary mitral regurgitation, the reduced mortality with TMVr in the overall COAPT study population was not observed in the subgroup of patients with PAD. However, TMVr reduced HF hospitalizations and improved health status and exercise capacity consistently in patients with and without PAD. Registration Clinical Trial Name: Cardiovascular Outocmes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (The COAPT Trial); URL: https://www.clinicaltrials.gov/; Unique identifier: NCT01626079. https://clinicaltrials.gov/ct2/show/NCT01626079

Background Diabetes mellitus and high platelet reactivity (HPR) on clopidogrel are both associated with increased risk of ischemic events after percutaneous coronary intervention, but whether the HPR‐associated risk of adverse ischemic events differs by diabetes mellitus status is unknown. Methods and Results ADAPT‐DES (Assessment of Dual Antiplatelet Therapy With Drug‐Eluting Stents) was a prospective, multicenter registry of patients treated with coronary drug‐eluting stents. HPR was defined as P2Y12 reaction units >208 by the VerifyNow point‐of‐care assay. Cox multivariable analysis was used to assess whether HPR‐associated risk of major adverse cardiac events (MACE; cardiac death, myocardial infarction, or stent thrombosis) varied for patients with insulin‐treated diabetes mellitus (ITDM), non–ITDM, and no diabetes mellitus. Diabetes mellitus and HPR were included in an interaction analysis. Of 8582 patients enrolled, 2429 (28.3%) had diabetes mellitus, of whom 998 (41.1%) had ITDM. Mean P2Y12 reaction units were higher in patients with diabetes mellitus versus without diabetes mellitus, and HPR was more frequent in patients with diabetes mellitus. HPR was associated with consistently increased 2‐year rates of MACE in patients with and without diabetes mellitus (Pinteraction=0.36). A significant interaction was present between HPR and non–insulin‐treated diabetes mellitus versus ITDM for 2‐year MACE (adjusted hazard ratio [HR] for non–ITDM, 2.28 [95% CI, 1.39–3.73] versus adjusted HR for ITDM, 1.02 [95% CI, 0.70–1.50]; Pinteraction=0.01). Conclusions HPR was more common in patients with diabetes mellitus and was associated with an increased risk of MACE in both patients with and without diabetes mellitus. In patients with diabetes mellitus, a more pronounced effect of HPR on MACE was present in lower‐risk non–ITDM patients than in higher‐risk patients with ITDM. Registration URL: https://clinicaltrials.gov/ct2/show/NCT00638794; Unique identifier: NCT00638794. ADAPT‐DES (Assessment of Dual Antiplatelet Therapy With Drug‐Eluting Stents).

Background Use of the modified American College of Cardiology (ACC)/American Heart Association (AHA) lesion classification as a prognostic tool to predict short‐ and long‐term clinical outcomes after percutaneous coronary intervention in the modern drug‐eluting stent era is uncertain. Methods and Results Patient‐level data from 7 prospective, randomized trials were pooled. Clinical outcomes of patients undergoing single lesion percutaneous coronary intervention with second‐generation drug‐eluting stent were analyzed according to modified ACC/AHA lesion class. The primary end point was target lesion failure (TLF: composite of cardiac death, target vessel myocardial infarction, or ischemia‐driven target lesion revascularization). Clinical outcomes to 5 years were compared between patients treated for noncomplex (class A/B1) versus complex (class B2/C) lesions. Eight thousand five hundred sixteen patients (age 63.1±10.8 years, 70.5% male) were analyzed. Lesions were classified as A, B1, B2, and C in 7.9%, 28.5%, 33.7%, and 30.0% of cases, respectively. Target lesion failure was higher in patients undergoing percutaneous coronary intervention of complex versus noncomplex lesions at 30 days (2.0% versus 1.1%, P=0.004), at 1 year (4.6% versus 3.0%, P=0.0005), and at 5 years (12.4% versus 9.2%, P=0.0001). By multivariable analysis, treatment of ACC/AHA class B2/C lesions was significantly associated with higher rate of 5‐year target lesion failure (adjusted hazard ratio, 1.39 [95% CI, 1.17–1.64], P=0.0001) driven by significantly higher rates of target vessel myocardial infarction and ischemia‐driven target lesion revascularization. Conclusions In this pooled large‐scale analysis, treating complex compared with noncomplex lesions according to the modified ACC/AHA classification with second‐generation drug‐eluting stent was associated with worse 5‐year clinical outcomes. This historical classification system may be useful in the contemporary era for predicting early and late outcomes following percutaneous coronary intervention.

Background The long‐term course of coronary atherosclerosis has not been studied in large nationwide cohorts. Understanding the natural history of coronary atherosclerosis could help identify patients at risk for future coronary events. Methods and Results All coronary artery segments with

Abstract. Intravenous anticoagulant therapy is critical to prevent ischemic recurrences and complications without increasing the risk of bleeding in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). It includes the indirect thrombin inhibitor heparins and the direct thrombin inhibitor bivalirudin. However, the ideal anticoagulant for patients undergoing PPCI remains controversial. In this review, we provide an overview of currently available anticoagulant therapies used in STEMI patients undergoing PPCI, including describing the rationale for their use, pivotal clinical trial data, and treatment recommendations of guidelines, providing much-needed clarity to guide the selection of the safest and most effective anticoagulant regimens for PPCI.

Background: Reshaping the dilated left ventricle using a surgically implanted papillary muscle sling has been shown to provide long-term improvement in cardiac function compared to annuloplasty alone in patients with systolic heart failure. A papillary muscle sling which can be implanted via a transcatheter approach has the potential to make this treatment more widely available to patients. Methods: The Vsling transcatheter papillary muscle sling device was evaluated in a chronic animal model (sacrificed at 30 and 90 days), in a simulator, and in a human cadaver. Results: The Vsling device was successfully implanted in 10 pigs, 6 simulator procedures, and 1 human cadaver. Procedure complexity and device usability were rated as reasonable or better by 6 interventional cardiologists. Gross and histological analysis in chronic pigs through 90 days demonstrated near-complete endothelial coverage with mild inflammation and small hematoma formation but without adverse tissue reactions, thrombi, or embolization. Conclusions: Preliminary feasibility and safety of the Vsling implant and implantation procedure have been demonstrated. Human trials are planned to begin in the summer of 2022.

Statins, which have anti-inflammatory and antithrombotic properties, could have effects in COVID-19 patients. Here, the authors find in a retrospective analysis of patients hospitalized with COVID-19 that antecedent statin use is associated with lower inpatient mortality.

Abstract Background We investigated the association of insulin resistance (IR) with coronary plaque morphology and the risk of cardiovascular events in patients enrolled in the Providing Regional Observations to Study Predictors of Events in Coronary Tree (PROSPECT) study. Methods Patients with acute coronary syndromes (ACS) were divided based on DM status. Non-DM patients were further stratified according to homeostasis-model-assessment IR (HOMA-IR) index as insulin sensitive (IS; HOMA-IR ≤ 2), likely-IR (LIR; 2

Abstract Background Transcatheter aortic valve replacement (TAVR) is increasingly used to treat patients with severe aortic stenosis (AS). Cardiovascular magnetic resonance imaging (CMR) provides reliable and reproducible estimates for assessment of cardiac structure and function after TAVR. The goal of this study was to conduct a systematic review and meta-analysis of the literature to assess left ventricular (LV) volumes, mass and function by CMR after TAVR. Methods Using Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines, we searched PubMed and Embase for studies reporting CMR findings before and at least 1 month after TAVR. Main factors of interest were LV end-diastolic volume index (LVEDVi), LV end-systolic volume index (LVESVi), LV mass index (LVMi), and left ventricular ejection fraction (LVEF). Standardized mean differences (SMD) were pooled by random effects meta-analytic techniques. Results Of 453 screened publications, 10 studies (published between 2012 and 2018) were included. A total of 305 patients completed pre- and post-TAVR follow-up CMR (mean age range 78.6–85.0 years, follow-up range 6–15 months). Random effects analysis showed TAVR resulted in reduced LVEDVi (SMD: -0.25, 95% CI: − 0.43 to − 0.07, P = 0.006), LVESVi (SMD: -0.24, 95% CI: − 0.44 to − 0.05, P = 0.01), LVMi (SMD: -0.82, 95% CI: − 1.0 to − 0.63, P 0.05 for all). The median reduction was 4 ml/m2 (IQR: 3.1 to 8.2) for LVEDVi, 5 ml/m2 (IQR: 3.0 to 6.0) for LVESVi, and 15.1 g/m2 (IQR: 11.8 to 18.3) for LVMi. The median increase for LVEF was 3.4% (IQR 1.0 to 4.6%). Conclusions CMR demonstrates reverse LV remodeling occurrs within 6–15 months after TAVR, with reductions in LVEDVi, LVESVi and LVMi, and increased LVEF.

Background In participants with concomitant chronic coronary disease and advanced chronic kidney disease (CKD), the effect of treatment strategies on the timing of dialysis initiation is not well characterized. Methods and Results In ISCHEMIA‐CKD (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches–Chronic Kidney Disease), 777 participants with advanced CKD and moderate or severe ischemia were randomized to either an initial invasive or conservative management strategy. Herein, we compare the proportion of randomized participants with non–dialysis‐requiring CKD at baseline (n=362) who initiated dialysis and compare the time to dialysis initiation between invasive versus conservative management arms. Using multivariable Cox regression analysis, we also sought to identify the effect of invasive versus conservative chronic coronary disease management strategies on dialysis initiation. At a median follow‐up of 23 months (25th–75th interquartile range, 14–32 months), dialysis was initiated in 18.9% of participants (36/190) in the invasive strategy and 16.9% of participants (29/172) in the conservative strategy (P=0.22). The median time to dialysis initiation was 6.0 months (interquartile range, 3.0–16.0 months) in the invasive group and 18.2 months (interquartile range, 12.2–25.0 months) in the conservative group (P=0.004), with no difference in procedural acute kidney injury rates between the groups (7.8% versus 5.4%; P=0.26). Baseline clinical factors associated with earlier dialysis initiation were lower baseline estimated glomerular filtration rate (hazard ratio [HR] associated with 5‐unit decrease, 2.08 [95% CI, 1.72–2.56]; P

Coronary artery disease (CAD) is the most common cause of left ventricular systolic dysfunction (LVSD) and heart failure (HF). Revascularization with coronary artery bypass grafting (CABG) reduces all-cause mortality compared with medical therapy alone for these patients. Despite this, CABG is performed in a minority of patients with HF, partly due to patient unwillingness or inability to undergo major cardiac surgery and partly due to physician reluctance to refer for surgery due to high operative risk. Percutaneous coronary intervention (PCI) is a less-invasive method of revascularization that has the potential to reduce periprocedural complications compared with CABG in patients with HF. Recent advances in PCI technology and technique have made it realistic to achieve more complete revascularization with PCI in high-risk patients with HF, although no randomized controlled clinical trials (RCTs) of PCI in HF compared with either medical therapy or CABG have been performed. In this review, we discuss the currently available evidence for PCI in HF and the association between the extent of revascularization and clinical outcomes in HF. We also review recent advances in PCI technology and techniques with the potential to improve clinical outcomes in HF. Finally, we discuss emerging clinical trial evidence of revascularization in HF and the large, persistent evidence gaps that should be addressed with future clinical trials of revascularization in HF.

Background: Coronary calcification impairs stent delivery and optimal expansion, a significant predictor of subsequent stent thrombosis and restenosis. Current calcium ablative technologies may be limited by guidewire bias and periprocedural complications. Intravascular lithotripsy (IVL) delivers acoustic pressure waves to modify calcium, enhance vessel compliance, and optimize stent deployment. The Disrupt CAD III study demonstrated high (92.4%) procedural success and low (7.8%) 30-day major adverse cardiac event (MACE) rates following IVL, but longer term follow-up is required to determine the durability of clinical benefit and the late impact of optimized stent implantation associated with IVL. This analysis evaluates 1-year outcomes from the Disrupt CAD III study. Methods: Disrupt CAD III (NCT03595176) was a prospective, single-arm approval study designed to assess the safety and effectiveness of IVL as an adjunct to coronary stenting in de novo, severely calcified coronary lesions (n = 384). MACE was defined as the composite of cardiac death, myocardial infarction (MI), or ischemia-driven target vessel revascularization; target lesion failure was defined as cardiac death, MI, or ischemia-driven target lesion revascularization (ID-TLR). Results: At 1 year, MACE occurred in 13.8% of patients (cardiac death: 1.1%, MI: 10.5%, ischemia-driven target vessel revascularization: 6.0%) and target lesion failure occurred in 11.9% (ID-TLR: 4.3%), both driven by non-Q-wave MI (9.2%). Stent thrombosis (definite or probable) occurred in 1.1% of patients (including 1 event [0.3%] beyond 30 ​days). Conclusions: Disrupt CAD III represents the largest long-term (1-year) analysis of coronary IVL to date. IVL treatment prior to coronary stent implantation in severely calcified lesions was associated with low 1-year rates of MACE, ID-TLR, and stent thrombosis.

Background: Coronary artery calcification increases the procedural complexity of percutaneous coronary intervention and is associated with worse outcomes, especially in women. Intravascular lithotripsy (IVL) has been demonstrated to be safe and effective for vessel preparation in severely calcified stenotic lesions before stent implantation. Sex-based outcomes of IVL-facilitated stenting have not been defined. Methods: We performed a patient-level pooled analysis of the 4 prospective, single-arm Disrupt CAD studies that evaluated the safety and efficacy of IVL-facilitated stenting. Patient baseline and procedural characteristics and clinical outcomes were examined based on sex. The primary safety end point was 30-day major adverse cardiovascular events, defined as the composite of cardiac death, myocardial infarction, or target vessel revascularization. The primary efficacy end point was procedural success, defined as stent delivery with residual in-stent stenosis ≤30% without in-hospital major adverse cardiovascular events. Results: A total of 628 patients were included, of which 144 (22.9%) were women. Women were older (P < .001) and more likely to have hyperlipidemia (P = .03), renal insufficiency (P = .05), and prior myocardial infarction (P = .05). Women had smaller mean reference vessel diameter (2.7 ​ ± ​0.4 ​mm vs 3.0 ​ ± ​0.5 ​mm, P < .001), shorter lesion length (22.4 ​ ± ​10.3 ​mm vs 25.0 ​ ± ​11.7 ​mm, P = .01), and less side branch involvement (22.9% vs 32.4%, P = .03). Severe coronary calcification defined by angiography, stent delivery success, lesion predilatation, post-IVL dilatation, and poststent dilatation was similar between groups. There were no significant differences between women and men in the primary safety end point (8.3% vs 7.1%, P = .61; adjusted odds ratio 1.66; 95% confidence interval 0.78, 3.34; P = .17) or the primary efficacy end point (91.7% vs 92.6%, P = .72; adjusted odds ratio 0.58; 95% confidence interval 0.29, 1.24; P = .15). Post-IVL serious angiographic complications (flow-limiting dissection, perforation, abrupt closure, slow flow, no reflow) were similar for women and men (1.6% vs 2.3%, P = .75). Conclusions: Despite more comorbidities and smaller vessel size, IVL-facilitated stenting of severely calcified lesions achieves similar safety and efficacy in women and men.

Importance: S100A12 is a calcium binding protein which is involved in inflammation and progression of atherosclerosis.Objective: We sought to investigate the utility of S100A12 as a biomarker for the early diagnosis and prognostication of patients presenting with ST-segment elevation myocardial infarction (STEMI).Design, Setting, and Participants: S100A12 was measured in 1023 patients presenting to the emergency department with acute chest pain between June 2012 and November 2015. An independent cohort of 398 patients enrolled at 3 different hospitals served as a validation cohort.Main Outcomes and Measures: The primary clinical endpoint of interest was major adverse cardiac and cerebral events (MACCE) defined as a composite of all-cause death, MI, stroke, or hospitalization for heart failure.Results: A total of 438/1023 patients (42.8%) in the diagnosis cohort were adjudicated as STEMI, among whom plasma S100A12 levels increased within 30 min and peaked 1–2 h after symptom onset. Compared with high-sensitivity cardiac troponin T and creatine kinase-MB isoenzyme, S100A12 more accurately identified STEMI, especially within the first 2 h after symptom onset (area under the curve 0.963 compared with 0.860 for hscTnT and 0.711 for CK-MB, both P < 0.05). These results were consistent in the 243-patient validation cohort. The 1-year rate of MACCE was greatest in patients in the highest peak S100A12 tertile, intermediate in the middle tertile and least in the lowest tertile (9.3 vs. 5.7 vs. 3.0% respectively, Ptrend = 0.0006). By multivariable analysis the peak plasma concentration of S100A12 was an independent predictor of MACCE within 1 year after STEMI (HR, 1.001, 95%CI, 1.000–1.002; P = 0.0104).Conclusions and Relevance: S100A12 rapidly identified patients with STEMI, more accurately than other cardiac biomarkers, especially within the first 2 h after symptom onset. The peak plasma S100A12 level was a strong predictor of 1-year prognosis after STEMI.

Study objective: The Coronary Vasomotor Disorders International Study Group (COVADIS) invited leading experts to address strategies to enhance our clinical understanding of INOCA with an emphasis on the management of coronary vasomotor disorders. Design: Under-recognition of coronary vasomotor disorders, distinguishing different presentations of angina due to vasospasm and/or abnormal microvascular vasodilatation, developing invasive/non-invasive testing and treatment protocols, integrating diagnostic protocols into cardiologists' workflow and trials to inform guideline development were identified as key knowledge gaps and will be briefly addressed in this Viewpoint article. Setting: Virtual international meeting. Participants: Leading international experts in ischemic heart disease with no obstructive coronary artery disease. Interventions: None. Main outcome measures: None. Results: Topics discussed include: 1. Obstructive epicardial disease, functional vasospasm and microvascular disorders; 2. Under-recognition of coronary vasomotor disorders in clinical practice; 3. Complexity of coronary vasomotor disorders; 4. Understanding different presentations - vasospastic disease and microvascular angina; 5. Invasive/noninvasive testing and treatment protocols for vasospasm and microvascular angina assessment; 6. Treatment challenges; 7. Integrating diagnostic protocols into cardiologists' workflow; 8. The path forward to advance our approach to managing myocardial ischemia. Conclusions: Obstructive epicardial disease, functional vasospasm and microvascular disorders often co-exist and contribute to myocardial ischemia. Under-recognition, the complexity of coronary vasomotor disorders, understanding different presentations, testing and treatment protocols, treatment challenges, and integrating diagnostic protocols into cardiologists' workflow all contribute to the path forward to advance our management of myocardial ischemia for improved patient outcomes.

Background: Peripheral artery disease (PAD) is associated with an increased risk of ischemic events following percutaneous coronary intervention (PCI). More aggressive antiplatelet therapy may mitigate this risk. The present study evaluates the efficacy of cangrelor in patients with PAD undergoing PCI. Methods and results: This is a pooled analysis from the CHAMPION PCI, CHAMPION PLATFORM, AND CHAMPION PHOENIX trials, evaluating cangrelor versus either clopidogrel or placebo in PCI patients. The occurrence of the primary endpoint of death, myocardial infarction, or ischemia-driven revascularization (IDR) was assessed in patients with and without PAD. GUSTO severe bleeding at 48 h was also evaluated. There were 1720 (7%) patients with PAD and 22,802 (93%) without PAD. After adjustment for differences in baseline variables, PAD patients, compared with those without PAD, experienced increased odds of the primary endpoint (OR [95% CI] = 1.27 [0.91, 1.77], P = 0.16) and GUSTO severe bleeding (OR [95% CI] = 3.24 [1.28, 8.21], P = 0.01). In PAD patients, the primary endpoint was 4.7% with cangrelor vs. 7.2% with clopidogrel (OR [95% CI] = 0.64 [0.42,0.96]); in patients without PAD the primary endpoint was 3.5% with cangrelor vs. 4.2% with clopidogrel (OR [95% CI] = 0.83 [0.72,0.95]), P-interaction 0.23. Among patients with or without PAD, there was no significant difference in the rate of GUSTO severe bleeding with cangrelor compared with control, P-interaction 0.86. Conclusions: In a pooled analysis of the CHAMPION studies, PAD was associated with increased rates of ischemic and bleeding complications. Cangrelor reduced the odds of ischemic events, without increasing GUSTO severe bleeding. Clinical trial registration: clinicaltrials.gov identifiers: CHAMPION PCI (NCT00305162), CHAMPION PLATFORM(NCT00385138), CHAMPION PHOENIX (NCT01156571)

Abstract Guideline‐based medical therapy is the foundation of treatment for individuals with coronary artery disease. However, revascularization with either percutaneous coronary intervention or coronary artery bypass grafting may be beneficial in patients with acute coronary syndromes, refractory symptoms, or in other specific scenarios (eg, left main disease and heart failure). While the goal of percutaneous coronary intervention and coronary artery bypass grafting is to achieve complete revascularization, anatomical and ischemic definitions of complete revascularization and their methodology for assessment remain highly variable. Such lack of consensus invariably contributes to the absence of standardized approaches for invasive treatment of coronary artery disease. Herein, we propose a novel, comprehensive, yet pragmatic algorithm with both anatomical and ischemic parameters that aims to provide a systematic method to assess complete revascularization after percutaneous coronary intervention or coronary artery bypass grafting in both clinical practice and clinical trials.

Background: Conventional statistical methods used in clinical trials lack the ability to predict patient specific risk and very often do not consider the effects of time varying interventions. The aim of this study is to test a novel artificial neural network based model for clinical trial analysis to represent the continuous time evolution of risk. Methods: The novel methodology tested utilizes system dynamics and artificial neural networks. This methodology was applied to analyze data from 2,221 patients with acute myocardial infarction enrolled in a well characterized randomized study, the HORIZONS-AMI trial. Outcomes analyzed included: (1) target lesion revascularization (TLR) and (2) stent thrombosis. The proposed neural system dynamics (NSD) model was compared against traditional Cox Proportional Hazards (Cox PH) and Cox neural network (NN) models. Model performance was evaluated using C-statistic at 1, 2 -and 3- years follow-up and model-based simulation studies were performed to examine the effect of different variables on the predicted risk of TLR and stent thrombosis. Results: The NSD model achieved comparable performance to Cox models for TLR. For stent thrombosis, the NSD model outperformed Cox models (1-year C-statistic: Stent thrombosis – Cox PH: 0.60, Cox NN: 0.66, neural SD model: 0.69). The neural SD model identified clinically relevant variables such as stent count, stent type and multiple lesions treated as significant predictors for TLR; and stent count and peak platelet count for stent thrombosis. Simulations illustrated change in predicted TLR risk maximal for the neural SD model, compared to other models. For stent thrombosis, simulation scenario illustrated predicted event rate doubling when clopidogrel is discontinued at 6 months compared to extended use. Conclusions: We have demonstrated an alternative analytical methodology that combines system dynamics and artificial neural networks to analyze results from a randomized trial. This novel approach can incorporate patient-specific longitudinal data and provide personalized risk prediction.

Introduction The previously published SYNTAX III REVOLUTION trial demonstrated that clinical decision-making between coronary artery bypass graft (CABG) and percutaneous coronary intervention based on coronary CT angiography (CCTA) had a very high agreement with the treatment decision derived from invasive coronary angiography (ICA). The study objective of the FASTTRACK CABG is to assess the feasibility of CCTA and fractional flow reserve derived from CTA (FFRCT) to replace ICA as a surgical guidance method for planning and execution of CABG in patients with three-vessel disease with or without left main disease.Methods and analysis The FASTTRACK CABG is an investigator-initiated single-arm, multicentre, prospective, proof-of-concept and first-in-man study with feasibility and safety analysis. Surgical revascularisation strategy and treatment planning will be solely based on CCTA and FFRCT without knowledge of the anatomy defined by ICA. Clinical follow-up visit including CCTA will be performed 30 days after CABG in order to assess graft patency and adequacy of the revascularisation with respect to the surgical planning based on non-invasive imaging (CCTA) with functional assessment (FFRCT) and compared with ICA. Primary feasibility endpoint is CABG planning and execution solely based on CCTA and FFRCT in 114 patients. Primary safety endpoint based on 30 day CCTA is graft assessment and topographical adequacy of the revascularisation procedure. Automatic non-invasive assessment of functional coronary anatomy complexity is also evaluated with FFRCT for functional Synergy Between percutaneous coronary intervention With Taxus and Cardiac Surgery Score assessment on CCTA. CCTA with FFRCT might provide better anatomical and functional analysis of the coronary circulation leading to appropriate anatomical and functional revascularisation, and thereby contributing to a better outcome.Ethics and dissemination Each patient has to provide written informed consent as approved by the ethical committee of the respective clinical site. Results will be submitted for publication in peer-reviewed journals and will be disseminated at scientific conferences.Trial registration number NCT04142021.

Background: The aim of this clinical research was to investigate the effects of Pressure-controlled intermittent Coronary Sinus Occlusion (PiCSO) on infarct size at 5 days after primary percutaneous coronary intervention (pPCI) in patients with ST-segment elevation myocardial infarction (STEMI). Methods and results: This comparative study was carried out in four UK hospitals. Forty-five patients with anterior STEMI presenting within 12 h of symptom onset received pPCI plus PiCSO (initiated after reperfusion; n = 45) and were compared with a propensity score-matched control cohort from INFUSE-AMI (n = 80). Infarct size (% of LV mass, median [interquartile range]) measured by cardiac magnetic resonance (CMR) at day 5 was significantly lower in the PiCSO group (14.3% [95% CI 9.2–19.4%] vs. 21.2% [95% CI 18.0–24.4%]; p = 0.023). There were no major adverse cardiac events (MACE) related to the PiCSO intervention. Conclusions: PiCSO, as an adjunct to pPCI, was associated with a lower infarct size at 5 days after anterior STEMI in a propensity score-matched population.

Background For patients with ST‐segment–elevation myocardial infarction (STEMI) and multivessel coronary artery disease, the optimal treatment of the non‐infarct‐related artery has been controversial. This up‐to‐date meta‐analysis focusing on individual clinical end points was performed to further evaluate the benefit of complete revascularization with percutaneous coronary intervention for patients with STEMI and multivessel coronary artery disease. Methods and Results We systematically identified all randomized trials comparing complete revascularization with percutaneous coronary intervention to culprit‐only revascularization for multivessel disease in STEMI and performed a random‐effects meta‐analysis. The primary efficacy end point was cardiovascular death analyzed on an intention‐to‐treat basis. Secondary end points included all‐cause mortality, myocardial infarction, and unplanned revascularization. Ten studies (7542 patients) were included: 3664 patients were randomized to complete revascularization and 3878 to culprit‐only revascularization. Across all patients, complete revascularization was superior to culprit‐only revascularization for reduction in the risk of cardiovascular death (relative risk [RR], 0.68; 95% CI, 0.47–0.98; P=0.037; I2=21.8%) and reduction in the risk of myocardial infarction (RR, 0.65; 95% CI, 0.54–0.79; P