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Background:To date, there is no data on switching to dual pathway inhibition (DPI) patients who have completed a guideline-recommended dual antiplatelet therapy (DAPT) regimen. Objectives: To assess the feasibility of switching from DAPT to DPI and to compare the pharmacodynamic (PD) profiles of these treatments. Methods: This was a prospective, randomized, PD study conducted in 90 patients with chronic coronary syndrome (CCS) on DAPT with aspirin (81mg/qd) plus a P2Y12 inhibitor [clopidogrel (75 mg/qd; n=30), ticagrelor (90mg/bid; n=30), or prasugrel (10mg/qd; n=30)]. Patients in each cohort were randomized to maintain DAPT or switch to DPI (aspirin 81mg/qd plus rivaroxaban 2.5mg/bid). PD assessments included: VerifyNow P2Y12 reaction units; light transmittance aggregometry following stimuli with adenosine diphosphate (ADP), tissue factor (TF), and a combination of collagen, ADP, and TF (CATF, maximum platelet aggregation %); thrombin generation (TG). Assays were performed at baseline and 30 days post-randomization. Results: Switching from DAPT to DPI occurred without major side effects. DAPT was associated with enhanced P2Y12 inhibition, while DPI with reduced TG. Platelet-mediated global thrombogenicity (primary endpoint) showed no differences between DAPT and DPI in the ticagrelor (14.5% [0.0–63.0] vs. 20.0% [0.0–70.0]; p=0.477) and prasugrel (20.0% [0.0–66.0] vs. 4.0% [0.0–70.0]; p=0.482), but not clopidogrel (27.0% [0.0–68.0] vs. 53.0% [0.0–81.0]; p=0.011), cohorts. Conclusion: In patients with CCS, switching from different DAPT regimens to DPI was feasible, showing enhanced P2Y12 inhibition with DAPT and reduced TG with DPI, with no differences in platelet-mediated global thrombogenicity between DPI and ticagrelor- and prasugrel, but not clopidogrel-, based DAPT.

The impact of intense low-density lipoprotein cholesterol (LDL-C) reduction using a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor on profiles of platelet reactivity has yet to be explored.Our aim was to investigate the effects of the PCSK9 inhibitor, evolocumab, on platelet reactivity in patients with atherosclerotic cardiovascular disease (ASCVD) on clopidogrel treatment.This was a prospective, randomised, double-blind, placebo-controlled pharmacodynamic study in patients with ASCVD on clopidogrel treatment and with LDL-C levels ≥70 mg/dL despite a maximally tolerated statin dose. Patients were stratified according to levels of platelet reactivity using VerifyNow P2YA total of 84 patients (HPR, n=37 [19 evolocumab vs 18 placebo]; NPR, n=47 [22 evolocumab vs 25 placebo]) were included. Evolocumab significantly reduced LDL-C compared to placebo at 14 (p0.001) and 30 (p=0.001) days. At 14 days, PRU levels were significantly lower with evolocumab compared to placebo in the HPR (218.2±29.7 vs 246.6±35.2; p=0.017), but not in the NPR cohort (141.2±42.8 vs 148.2±41.7; p=0.578). At 30 days, there were no significant differences in PRU in the HPR (219.3±38.3 vs 240.9±51.8; p=0.161) or NPR (141.5±54.3 vs 158.6±40.8; p=0.229) cohorts.Compared to placebo, evolocumab in adjunct to statin therapy did not significantly reduce platelet reactivity at 30 days in ASCVD patients on clopidogrel treatment despite intense LDL-C reduction. ClinicalTrials.gov: NCT03096288.

Objectives To rule out a drug-drug interaction (DDI) among cangrelor-treated patients who have been pre-treated with ticagrelor. Background There are no studies specifically designed to rule out a DDI when cangrelor is used among patients who have been pre-treated with ticagrelor. Methods In this prospective, randomized, double-blind, placebo-controlled, cross-over, pharmacokinetic (PK) and pharmacodynamic (PD) study, patients with coronary artery disease (n = 20) were pre-treated with a 180-mg ticagrelor loading dose (LD) and after 1 hour randomized to placebo or cangrelor (bolus and infusion for 2 hours). Patients crossed over after 1-4 weeks of washout. PK analysis included ticagrelor plasma levels and its active metabolite. PD assessments included: VerifyNow P2Y12 reaction units (PRU), light transmittance aggregometry vasodilatorstimulated phosphoprotein, and Total Thrombus-Formation Analysis System. PK/PD assessments were performed at 7-time points. Results Compared to placebo, adding cangrelor to patients pre-treated with ticagrelor resulted in a significant reduction in PRU at 30 min and 1 hour after starting infusion. At 2 hours after stopping cangrelor/placebo infusion, PRU was low and similar in both groups (16.9 vs. 12.6; mean difference: 4.3; 95%CI: -28.6; 37.3), meeting the non-inferiority primary endpoint (predefined non-inferiority margin 45 PRU). Consistent findings were shown with all PD assays. PK tracked PD findings with no differences between groups in plasma levels of ticagrelor and its metabolite. Conclusions Compared with placebo, the use of cangrelor in patients pre-treated with ticagrelor results in enhanced platelet inhibition with no differences in PK/PD profiles after discontinuation of drug infusion indicating the absence of a DDI.

Aims To assess the feasibility of switching from dual antiplatelet therapy (DAPT) to dual pathway inhibition (DPI) and to compare the pharmacodynamic (PD) profiles of these treatment regimens. Methods and results This was a prospective, randomized, PD study conducted in 90 patients with chronic coronary syndrome (CCS) on DAPT with aspirin (81 mg/qd) plus a P2Y12 inhibitor [clopidogrel (75 mg/qd; n = 30), ticagrelor (90 mg/bid; n = 30), or prasugrel (10 mg/qd; n = 30)]. Patients in each cohort were randomized to maintain DAPT or switch to DPI (aspirin 81 mg/qd plus rivaroxaban 2.5 mg/bid). PD assessments included: VerifyNow P2Y12 reaction units; light transmittance aggregometry following stimuli with adenosine diphosphate (ADP), tissue factor, and a combination of collagen, ADP, and TF (CATF, maximum platelet aggregation %); thrombelastograph coagulation analyzer; thrombin generation (TG). Assays were performed at baseline (on DAPT) and 30 days post-randomization (trough and peak). Switching from DAPT to DPI occurred without major side effects. DAPT was associated with enhanced P2Y12 inhibition, while DPI with reduced TG. Platelet-mediated global thrombogenicity (primary endpoint) showed no differences between DAPT and DPI in the ticagrelor (14.5% [0.0–63.0] vs. 20.0% [0.0–70.0]; p = 0.477) and prasugrel (20.0% [0.0–66.0] vs. 4.0% [0.0–70.0]; p = 0.482), but not clopidogrel (27.0% [0.0–68.0] vs. 53.0% [0.0–81.0]; p = 0.011), cohorts. Conclusion In patients with CCS, switching from different DAPT regimens to DPI was feasible, showing enhanced P2Y12 inhibition with DAPT and reduced TG with DPI, with no differences in platelet-mediated global thrombogenicity between DPI and ticagrelor- and prasugrel, but not clopidogrel-, based DAPT.

To rule out a drug-drug interaction (DDI) among cangrelor-treated patients who have been pre-treated with ticagrelor.There are no studies specifically designed to rule out a DDI when cangrelor is used among patients who have been pre-treated with ticagrelor.In this prospective, randomized, double-blind, placebo-controlled, cross-over, pharmacokinetic (PK) and pharmacodynamic (PD) study, patients with coronary artery disease (n=20) were pre-treated with a 180-mg ticagrelor loading dose (LD) and after 1 hour randomized to placebo or cangrelor (bolus and infusion for 2 hours). Patients crossed over after 1-4 weeks of washout. PK analysis included ticagrelor plasma levels and its active metabolite. PD assessments included: VerifyNow P2YCompared to placebo, adding cangrelor to patients pre-treated with ticagrelor resulted in a significant reduction in PRU at 30 min and 1 hour after starting infusion. At 2 hours after stopping cangrelor/placebo infusion, PRU was low and similar in both groups (16.9 vs. 12.6; mean difference: 4.3; 95%CI: -28.6; 37.3), meeting the non-inferiority primary endpoint (pre-defined non-inferiority margin 45 PRU). Consistent findings were shown with all PD assays. PK tracked PD findings with no differences between groups in plasma levels of ticagrelor and its metabolite.Compared with placebo, the use of cangrelor in patients pre-treated with ticagrelor results in enhanced platelet inhibition with no differences in PK/PD profiles after discontinuation of drug infusion indicating the absence of a DDI.

Cardiovascular disease (CVD) remains the leading cause of death in the United States. However, percutaneous interventional cardiovascular therapies are often underutilized in Blacks, Hispanics, and women and may contribute to excess morbidity and mortality in these vulnerable populations. The Society for Cardiovascular Angiography and Interventions (SCAI) is committed to reducing racial, ethnic, and sex-based treatment disparities in interventional cardiology patients. Accordingly, each of the SCAI Clinical Interest Councils (coronary, peripheral, structural, and congenital heart disease [CHD]) participated in the development of this whitepaper addressing disparities in diagnosis, treatment, and outcomes in underserved populations. The councils were charged with summarizing the available data on prevalence, treatment, and outcomes and elucidating potential reasons for any disparities. Given the huge changes in racial and ethnic composition by age in the United States (Figure 1), it was difficult to determine disparities in rates of diagnosis and we expected to find some racial differences in prevalence of disease. For example, since the average age of patients undergoing transcatheter aortic valve replacement (TAVR) is 80 years, one may expect 80% of TAVR patients to be non-Hispanic White. Conversely, only 50% of congenital heart interventions would be expected to be performed in non-Hispanic Whites. Finally, we identified opportunities for SCAI to advance clinical care and equity for our patients, regardless of sex, ethnicity, or race.

Visual Abstract, Highlights • Our study supports the feasibility of using rapid CYP2C19 genotyping among both patients with stable and acute coronary syndrome undergoing diagnostic coronary angiography, with intent to undergo ad hoc PCI, in real-world clinical practice. • Rapid bedside genetic testing assay allows for very rapid turnaround times of results, with patients approached the same day of their procedure and availability of CYP2C19 genotypes within 1 h of sampling and before patients undergoing PCI. • Among carriers of CYP2C19 loss-of-function alleles undergoing PCI there were no differences in levels of platelet inhibition between prasugrel and ticagrelor (loading and maintenance dosing)., Summary The feasibility of rapid genetic testing in patients undergoing percutaneous coronary intervention (PCI) and the comparison of the pharmacodynamic effects of prasugrel versus ticagrelor among carriers of cytochrome P450 2C19 loss-of-function alleles treated with PCI has been poorly explored. Rapid genetic testing using the Spartan assay was shown to be feasible and provides results in a timely fashion in a real-world setting of patients undergoing coronary angiography (n = 781). Among patients (n = 223, 28.5%), carriers of at least 1 loss-of-function allele treated with PCI (n = 65), prasugrel, and ticagrelor achieve similar levels of platelet inhibition. (A Pharmacodynamic Study Comparing Prasugrel Versus Ticagrelor in Patients Undergoing PCI With CYP2C19 Loss-of-function [NCT02065479])

Aims Dual pathway inhibition (DPI) by adding a vascular dose of rivaroxaban to a single antiplatelet agent has emerged as a promising antithrombotic strategy. However, in most studies the antiplatelet agent of choice used in adjunct to a vascular dose of rivaroxaban was aspirin, and data on a P2Y12 inhibitor and how this DPI regimen compares with standard dual antiplatelet therapy (DAPT) are limited. Methods and results This investigation was a substudy analysis conducted in selected cohorts of patients with stable atherosclerotic disease enrolled from a larger prospective, open-label, parallel-group pharmacodynamic (PD) study. We analysed data from 40 patients treated with either clopidogrel- or ticagrelor-based DAPT first, and clopidogrel- or ticagrelor-based DPI thereafter. PD measures explored key pathways involved in thrombus formation and included markers of (1) P2Y12 reactivity, (2) platelet-mediated global thrombogenicity, (3) cyclooxygenase-1 activity, (4) thrombin receptor-activating peptide (TRAP)-induced platelet aggregation, (5) tissue factor (TF)-induced platelet aggregation, and (6) thrombin generation. Compared with DAPT, on a background of the same P2Y12 inhibitor (clopidogrel or ticagrelor), DPI was associated with reduced thrombin generation, increased markers of cyclooxygenase-1 activity and TRAP-induced platelet aggregation, and no differences in markers of P2Y12 signalling, platelet-mediated global thrombogenicity, and TF-induced platelet aggregation. In an analysis according to P2Y12 inhibitor type, ticagrelor reduced markers of platelet-mediated global thrombogenicity, P2Y12 signalling, and rates of high platelet reactivity compared with clopidogrel. Conclusion Compared with DAPT with aspirin and a P2Y12 inhibitor, the use of a P2Y12 inhibitor in adjunct to a vascular dose of rivaroxaban as part of a DPI strategy is associated with similar effects on platelet-mediated global thrombogenicity but reduced thrombin generation. A DPI strategy with ticagrelor is associated with enhanced antithrombotic efficacy, the clinical implications of which warrant larger scale investigations. Clinical trial registration ClinicalTrials.gov identifier: NCT03718429.

Aim Inhibition of thrombin-mediated signaling processes using a vascular dose of rivaroxaban in adjunct to antiplatelet therapy, known as dual-pathway inhibition (DPI), reduces atherothrombotic events in patients with stable atherosclerotic disease. However, there are limited data on the pharmacodynamic (PD) effects of this strategy and how it compares to standard dual antiplatelet therapy (DAPT). Methods and Results This investigation was conducted in selected cohorts of patients (n = 40) with stable atherosclerotic disease—enrolled within a larger prospective, open-label, parallel-group PD study—who were treated with either aspirin plus clopidogrel (DAPT), aspirin plus rivaroxaban 2.5 mg/bid (DPI), or DAPT plus rivaroxaban 2.5 mg/bid. Multiple PD assays providing a comprehensive assessment of markers of thrombosis were used. PD endpoints included platelet-mediated global thrombogenicity measured by light transmittance aggregometry (LTA) following stimuli with CATF (collagen-related peptide + adenosine diphosphate [ADP] + tissue factor [TF]), markers of P2Y12 reactivity, markers of platelet aggregation using LTA following several stimuli (arachidonic acid, ADP, collagen, TF, and thrombin receptor-activating peptide [TRAP]), thrombin generation, and thrombus formation. There was no difference in platelet-mediated global thrombogenicity between groups. Rivaroxaban significantly reduced thrombin generation and was associated with a trend toward reduced TF-induced platelet aggregation. Clopidogrel-based treatments reduced markers of P2Y12 signaling and TRAP-induced platelet aggregation. There were no differences between groups on markers of cyclooxygenase-1-mediated activity. Conclusion Compared with DAPT, DPI does not result in any differences in platelet-mediated global thrombogenicity, but reduces thrombin generation. These PD observations suggest that modulating thrombin generation—by means of factor Xa inhibition—in adjunct to antiplatelet therapy provides effective antithrombotic effects, supporting the efficacy and safety findings of a DPI strategy observed in clinical trials.

Health care practices are influenced by variety of factors. These factors that include social determinants, race and ethnicity, and gender not only affect access to health care but can also affect quality of care and patient outcomes. These are a source of health care disparities. This article acknowledges that these disparities exist in getting optimal care in structural heart disease, reviews the literature and proposes steps that can help reduce these disparities on personal and committee levels.

Summary: Vorapaxar reduces thrombotic cardiovascular events at the expense of increased bleeding. However, the differential pharmacodynamic (PD) effects of vorapaxar according to diabetes mellitus (DM) status are unknown. Moreover, although withdrawal of aspirin has emerged as a bleeding reduction strategy, the PD effects of stopping aspirin in patients treated with vorapaxar also are unknown. In this prospective PD investigation, vorapaxar was associated with reduced platelet-mediated thrombogenicity without affecting clot kinetics irrespective of DM status. However, platelet-mediated thrombogenicity increased after aspirin withdrawal, particularly among patients with DM. (Optimizing anti-Platelet Therapy In diabetes MellitUS-5 Study [OPTIMUS-5]; NCT02548650) Key Words: dual antiplatelet therapy, pharmacodynamics, platelets, thrombin, vorapaxar

Objectives The aim of this study was to evaluate the incidence and outcomes of surgical bailout during transcatheter aortic valve replacement (TAVR). Background The incidence and outcomes of unplanned conversion to open heart surgery, or “surgical bailout,” during TAVR are not well characterized. Methods Data from the Society of Thoracic Surgeons/American College of Cardiology TVT (Transcatheter Valve Therapy) Registry was analyzed with respect to whether surgical bailout was performed during the index TAVR procedure. A Cox proportional hazards models was used to evaluate 1-year mortality and major adverse cardiovascular events. Results Between November 2011 and September 2015, a total of 47,546 patients underwent TAVR. Surgical bailout during TAVR was performed in 1.17% of the cases (n = 558); the most frequent indications were valve dislodgement (22%), ventricular rupture (19.9%), and aortic valve annular rupture (14.2%). The incidence of surgical bailout significantly decreased over time (first tertile 1.25%, second tertile 1.43%, third tertile 1.04%; p = 0.0088). The 30-day and 1-year incidence of major adverse cardiovascular events (54.6% vs. 7.4% [p Conclusions In a large, nationally representative registry, the need for surgical bailout in patients undergoing TAVR is low, and its incidence has decreased over time. However, surgical bailout after TAVR is associated with poor outcomes, including 50% mortality at 30 days.

Objectives The aim of this study was to assess if intravenous methylnaltrexone can counteract the effects of morphine on the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of ticagrelor. Background Morphine delays the onset of action of oral P2Y12 receptor inhibitors, including ticagrelor, by inhibiting gastric emptying and leading to delayed drug absorption. Methylnaltrexone is a peripheral opioid receptor antagonist that has the potential to prevent opioid-induced peripherally mediated side effects (e.g., gastric emptying inhibition) without affecting analgesia. Methods In this prospective, randomized, double-blind, placebo-controlled, crossover study, aspirin-treated patients with stable coronary artery disease (n = 30) were randomized to receive methylnaltrexone (0.3 mg/kg intravenous) or matching placebo. After methylnaltrexone or placebo administration, all patients received morphine (5 mg intravenous). This was followed 15 min later by a 180-mg loading dose of ticagrelor. Patients crossed over to the alternative study treatment after 7 ± 2 days of washout. PK and PD assessments were performed at 12 time points (6 pre- and 6 post-crossover). PK analysis included measurement of plasma levels of ticagrelor and its major active metabolite (AR-C124910XX). PD assessments included VerifyNow P2Y12, light transmittance aggregometry, and vasodilator-stimulated phosphoprotein. Results Only marginal changes in plasma levels of ticagrelor (and its major active metabolite) were observed with ticagrelor: maximum plasma concentration and area under the plasma concentration versus time curve from time 0 to the last measurable concentration were 38% and 30% higher, respectively, in patients receiving methylnaltrexone compared with those receiving placebo, but no differences in time to maximum plasma concentration were observed. There were no differences in P2Y12 reaction units by VerifyNow P2Y12 between groups at each time point, including 2 h (the primary endpoint; p = 0.261). Similarly, there were no differences in PD markers assessed by light transmittance aggregometry and vasodilator-stimulated phosphoprotein. Conclusions In patients with coronary artery disease receiving morphine, intravenous administration of the peripheral opioid receptor antagonist methylnaltrexone leads to only marginal changes in plasma levels of ticagrelor and its major metabolite, without affecting levels of platelet reactivity. (Effect of Methylnaltrexone on the PK/PD Profiles of Ticagrelor in Patients Treated With Morphine; NCT02403830)

Background: The platelet inhibitory effects induced by oral P2Y 12 receptor antagonists are delayed in patients with ST-segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention (P-PCI). In turn, this leads to a gap in platelet inhibition, exposing patients to an increased risk of early thrombotic complications and underscoring the need to define strategies associated with more effective platelet inhibition in the peri–primary percutaneous coronary intervention period. Cangrelor is an intravenous P2Y 12 inhibitor with prompt and potent antiplatelet effects. However, to date, there are limited data on the effects of cangrelor used in combination with ticagrelor in patients undergoing primary percutaneous coronary intervention. Moreover, questions have emerged on the potential for drug–drug interactions during the transition from cangrelor to oral P2Y 12 inhibitors. Methods: This was a prospective, randomized, double-blind, placebo-controlled pharmacodynamic study conducted in patients undergoing primary percutaneous coronary intervention (n=50) who were randomized to treatment with either cangrelor or matching placebo (bolus followed by 2-hour infusion). All patients received ticagrelor 180-mg loading dose administered as crushed tablets at the time of cangrelor/placebo bolus administration. Pharmacodynamic analyses were performed at 8 time points. Pharmacodynamic effects were measured as P2Y 12 reaction units by VerifyNow and platelet reactivity index by vasodilator-stimulated phosphoprotein. Results: Compared with placebo, cangrelor was associated with reduced P2Y 12 reaction units as early as 5 minutes after bolus, which persisted during the entire duration of drug infusion, including at 30 minutes (63 [32–93] versus 214 [183–245]; mean difference, 152 [95% CI, 108–195]; P Conclusions: In patients undergoing primary percutaneous coronary intervention, cangrelor is an effective strategy to bridge the gap in platelet inhibition associated with the use of oral P2Y 12 inhibition induced by ticagrelor. Ticagrelor can be administered as a crushed formulation concomitantly with cangrelor without any apparent drug–drug interaction. The clinical implications of these pharmacodynamic findings warrant investigation in an adequately powered clinical trial. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03247738

Aims Patients with diabetes mellitus (DM) and chronic kidney disease (CKD) are at increased risk of atherothrombotic events. Ticagrelor reduces ischaemic events compared to clopidogrel, with the greatest risk reduction in patients with both DM and CKD. How CKD status affects the pharmacodynamic (PD) and pharmacokinetic (PK) profiles of different ticagrelor maintenance dose regimens in patients with DM is unknown. Methods and results In this randomized, crossover study, patients with DM on treatment with dual antiplatelet therapy (aspirin and clopidogrel) were stratified according to CKD status and randomized to ticagrelor 90 or 60 mg bid. PK/PD assessments were performed at baseline, after 7–10 days of ticagrelor (peak and trough), and after 7–10 days of alternative ticagrelor regimen (peak and trough). PK assessments included plasma concentrations of ticagrelor and its major metabolite. PD assessments included vasodilator-stimulated phosphoprotein (VASP)–platelet reactivity index (PRI), VerifyNow P2Y12, and light transmittance aggregometry (LTA). A total of 92 patients with DM (CKD, n = 44; non-CKD, n = 48) were randomized. Levels of platelet reactivity were lower with the 90 mg compared with the 60 mg ticagrelor dose, which was statistically significant in non-CKD but not in CKD patients for most PD measures. There were no significant differences in the primary endpoint (trough levels of VASP–PRI following ticagrelor 90 mg dosing) between cohorts (31 ± 20 vs. 25 ± 14; P = 0.105). VerifyNow and LTA provided similar findings. PK assessments tracked PD profiles showing increased plasma concentrations of ticagrelor and its major metabolite in CKD compared to non-CKD patients. Conclusion In patients with DM, although ticagrelor maintenance dose regimens (60 and 90 mg) yield potent P2Y12 inhibition, levels of platelet reactivity tended to be higher and subject to broader variability in non-CKD compared with CKD patients. Clinical trial registration http://www.clinicaltrials.gov Unique Identifier: NCT02539160.

Background: Diabetes mellitus (DM) is a key risk factor for the development of chronic kidney disease (CKD) and patients having both risk factors have increased risk of atherothrombotic events, underscoring the importance of antiplatelet therapy. Ticagrelor reduces ischemic events compared with clopidogrel, with the greatest risk reduction in patients with both DM and CKD. However, how CKD status affects the pharmacodynamic (PD) and pharmacokinetic (PK) profiles of different ticagrelor dosing regimens in DM patients is unknown. Methods: This was a prospective, randomized, cross-over study testing the PD/PK profiles of ticagrelor 90mg bid and 60mg bid among DM patients with and without CKD. All patients had coronary artery disease and were on dual antiplatelet therapy with aspirin (81mg qd) and clopidogrel (75mg qd). PD and PK assessments were performed at 3 visits: baseline, after 7-10 days of ticagrelor therapy (pre-crossover; peak and trough), and after 7-10 days of alternative ticagrelor regimen (post-crossover; peak and trough). Results: A total of 92 patients were randomized (CKD-, n=48; CKD+, n=44). Platelet reactivity as assessed by multiple assays (VASP-PRI; VerifyNow P2Y12; LTA) was increased with 60mg compared with 90 mg, which was statistically significant in CKD- but not in CKD+ patients for most PD measures (Figure). Although trough levels of platelet reactivity were numerically lower in CKD+ patients compared with CKD-, there was no significant difference in the pre-defined primary endpoint (trough levels of VASP-PRI following ticagrelor 90 mg dosing) between DM subjects with and without CKD (31±20 vs 25±14; mean difference= 6.4; 95% CI: -1.1 to 14.3; p=0.105; primary endpoint; Figure). PK assessments tracked PD profiles. Conclusions: In patients with DM, platelet inhibition by ticagrelor is similar irrespective of CKD status. However, the PD effects of the 60mg ticagrelor regimen is reduced compared with the 90mg regimen in patients without CKD.

Background Vorapaxar as an adjunct to dual antiplatelet therapy ( DAPT ) reduces thrombotic events in patients with prior myocardial infarction at the expense of increased bleeding. Withdrawal of aspirin has emerged as a bleeding reduction strategy. The pharmacodynamic effects of vorapaxar with potent P2Y 12 inhibitors as well as the impact of dropping aspirin is unexplored and represented the aim of the VORA‐PRATIC (Vorapaxar Therapy in Patients With Prior Myocardial Infarction Treated With Newer Generation P2Y 12 Receptor Inhibitors Prasugrel and Ticagrelor) study. Methods and Results Post–myocardial infarction patients (n=130) on standard DAPT (aspirin+prasugrel or ticagrelor) were randomized to 1 of 3 arms: (1) triple therapy: aspirin+prasugrel/ticagrelor+vorapaxar; (2) dual therapy (drop aspirin): prasugrel/ticagrelor+vorapaxar; (3) DAPT : aspirin+prasugrel/ticagrelor. Pharmacodynamic assessments were performed at 3 time points (baseline and 7 and 30 days). Vorapaxar reduced CAT (collagen‐ADP‐TRAP)–induced platelet aggregation, a marker of platelet‐mediated global thrombogenicity (triple therapy versus DAPT at 30 days: mean difference=–27; 95% CI ,–35 to –19; P DAPT at 30 days: mean difference=–15; 95% CI ,–23 to –7; P P P 12 reactivity. Markers sensitive to aspirin‐induced effects increased ( P Conclusions In post–myocardial infarction patients treated with potent P2Y 12 inhibitors, vorapaxar reduces platelet‐driven global thrombogenicity, an effect that persisted, albeit attenuated, in the absence of aspirin and without affecting markers of P2Y 12 reactivity or clot kinetics. The clinical implications of these PD observations warrant future investigation. Registration URL : https://www.clini​caltr​ials.gov . Unique identifier: NCT 02545933.

Background: Adjunctive coronary atherectomy (CA) can be utilized in treating severely calcified coronary lesions; however, the temporal trends, patient selection, and variation in use of CA have not been well described. We sought to assess the trends in usage, interhospital variability, and outcomes with CA among patients undergoing percutaneous coronary intervention (PCI). Methods: All patients undergoing PCI in the National Cardiovascular Data Registry CathPCI Registry from July 1, 2009 to December 31, 2016 (N=3 864 377) were analyzed based on utilization of either rotational or orbital CA. Intervals using date of index CA grouped into 2009 Q3 to 2010, 2011 to 2012, 2013 to 2014, and 2015 to 2016 and hospital-level quartiles based on annual CA volumes were evaluated. The primary outcome measure was in-hospital major adverse cardiac events defined as a composite of all-cause mortality, periprocedural myocardial infarction, or stroke. Independent variables associated with outcomes were determined. Results: CA represented 1.7% (n=65 033) of the total PCI volume. Among hospitals performing PCI (n=1672), 577 (34.5%) did not perform any CA. Patients treated with CA were elderly, more often male, and had a history of diabetes, prior myocardial infarction, PCI, and coronary artery bypass grafting. The utilization of CA increased from 1.1% in Q3 2009 to 3.0% in Q4 of 2016 (5% quarterly increase in odds of CA; OR [95% CI], 1.05 [1.04–1.06], P P P P =0.01) and lower rates of PCI failure or complication requiring coronary artery bypass grafting (0.67 [0.56–0.79], P P Conclusions: Although CA is performed infrequently, its use has increased over time. After accounting for potential confounders, higher CA volume was associated with lower risk of major adverse events counterbalanced by small risk of coronary perforation.

Background: Vascular and bleeding complications were commonly reported in transcatheter aortic valve replacement clinical trials. Little is known about complication rates in contemporary US clinical practice or clinical outcomes associated with these complications. Methods: In the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry, we evaluated patients undergoing transcatheter aortic valve replacement from November 1, 2011 to June 30, 2016. The primary outcomes were in-hospital vascular complications and bleeding events. Secondary outcomes included all-cause mortality, stroke, and rehospitalization at 1 year. P values for trends were calculated for rates over time, and multivariable logistic regression was used to determine the association between vascular/bleeding complications and in-hospital clinical outcomes. Results: Overall, 34 893 patients undergoing transcatheter aortic valve replacement at 445 hospitals were analyzed. Of these, 9.3% (n=3257) experienced a vascular complication while 7.6% (n=2651) had an in-hospital bleeding event. Rates of both vascular complications and bleeding events decreased over time ( P value for trend test Conclusions: In patients undergoing transcatheter aortic valve replacement in the US, vascular complications and in-hospital bleeding events were common, but rates have declined over time with significant variation in complication rates across hospital sites. Vascular and bleeding complications are both associated with worse short- and long-term clinical outcomes including all-cause mortality. Further innovation to reduce sheath sizes and optimize antithrombotic therapy is necessary to reduce the incidence of these detrimental complications.

Background: The optimal treatment for concomitant two-vessel coronary artery disease (CAD) and moderate to severe ischemic mitral regurgitation (IMR) remains unclear. We compared the results of a staged percutaneous coronary intervention followed by minimally invasive mitral valve surgery (PCI+MIVS) versus combined coronary artery bypass graft and mitral valve surgery (CABG+MVS) in this population. Methods: All consecutive patients with two-vessel CAD and moderate to severe IMR, who underwent PCI+MIVS or CABG+MVS at our institution between February 2009 and April 2014, were retrospectively evaluated. Results: There were nine patients identified who underwent PCI+MIVS, and 15 who underwent CABG+MVS, with a mean age of 71±7, and 70±7 years, respectively (P=0.86). The remaining baseline characteristics were similar between both groups, with the exception of a higher prevalence of pre-operative clopidogrel administration (78% versus 27%, P=0.03) and left anterior descending plus left circumflex CAD (78% versus 27%, P=0.03), in those who underwent PCI+MIVS. The PCI+MIVS approach was associated with decreased mean cardiopulmonary bypass (111±41 versus 167±49 min, P=0.01) and aortic cross-clamp (79±32 versus 129±35 min, P=0.003) times, and less median number of intraoperative packed red blood transfusions {2 [interquartile range (IQR), 0–2] versus 3 units (IQR, 1–4), P=0.05}, when compared with CABG+MVS. The rate of mitral valve repair, postoperative complications, 30-day mortality, and 1-year survival did not differ between the surgical approaches. Conclusions: PCI+MIVS for two-vessel CAD and moderate to severe IMR is feasible, and associated with satisfactory outcomes, as compared with CABG+MVS.

ObjectiveA staged approach of percutaneous coronary intervention (PCI) followed by minimally invasive valve surgery (MIVS) is an alternative to the combined coronary artery bypass graft and valve surgery for patients with concomitant coronary artery (CAD) and valvular heart disease. We sought to evaluate the impact of the complexity of CAD, as assessed by the Syntax score, on the outcomes of the staged approach.MethodsWe retrospectively evaluated 138 patients who underwent PCI and MIVS at our institution between January 2009 and June 2013. The baseline Syntax score was calculated, and the patients were divided into two groups: low risk (Syntax scores, 0–22) or intermediate-high risk (>22).ResultsThere were 125 patients with low (mean ± standard deviation, 8 ± 5) and 13 with intermediate-high (mean ± standard deviation, 26 ± 4) Syntax scores. Baseline, PCI, and operative characteristics were similar between the groups, except for an observed higher incidence of peripheral arterial disease, multivessel coronary disease, mitral valve replacement, and a higher predicted The Society of Thoracic Surgeons mortality risk score in the intermediate-high Syntax group. The short-term postoperative complications, 30-day mortality, and 3-year survival (84% vs 77%) were similar between the groups. Patients in the intermediate-high-risk group had a higher incidence of repeat target vessel revascularization during follow-up (0.8% vs 16.7%).ConclusionsA staged approach of PCI followed by MIVS is a safe and feasible alternative for patients with valvular heart disease and concomitant CAD. However, it may confer an increased incidence of repeat target vessel revascularization in patients with intermediate- to high-complexity CAD.

A subset of patients requiring coronary revascularization and valve surgery may benefit from a combined approach of percutaneous coronary intervention (PCI) and valve surgery, as opposed to the standard median sternotomy approach of combined coronary artery bypass and valve surgery. To evaluate its potential benefits and limitations, a literature search was performed using PubMed EMBASE, Ovid, and the Cochrane library, through March 2016 to identify all studies involving a combined approach of PCI and valve surgery in patients with coronary artery and valvular disease. There were five studies included in the study with a total of 324 patients, of which 75 (23.1%) had a history of previous cardiac surgery. The interval between PCI and surgery ranged from simultaneous intervention to a median of 38 days (interquartile range, 18–65 days). The surgical approach performed consisted of a minimally invasive one or median sternotomy. There were 275 single valve surgery (84.9%) and 49 double-valve surgery (15.1%) with a 30-day mortality ranging from 0% to 5.5%. The 1-year survival ranged from 78% to 96%, and the follow-up period ranged from 1.3 to 5 years. Herein, we present a review of the literature using this technique.

Background Although clopidogrel is the most widely used P2Y12 inhibitor, loss-of-function (LOF) allelic variants located within the hepatic cytochrome P450 (CYP) 2C19 gene lead to attenuated bioactivation, increased rates of high platelet reactivity (HPR), and worse outcomes in patients undergoing percutaneous coronary intervention (PCI). Drug regulating authorities have suggested using alternative P2Y12 inhibitors (i.e., prasugrel or ticagrelor) in these patients. However, tailoring antiplatelet therapy in clinical practice according to results of genetic testing has been limited due to lack of access to promptly available results. Moreover, there are no head-to-head pharmacodynamic (PD) comparisons of prasugrel vs ticagrelor among patients with CYP2C19 LOF alleles. Purpose The aim of this study was to evaluate the feasibility of using rapid genetic testing in clinical practice and to compare the PD effects of prasugrel vs ticagrelor in patients undergoing PCI with CYP2C19 LOF alleles. Methods This was a prospective, randomized study conducted in patients with stable coronary artery disease and non-ST elevation acute coronary syndrome scheduled for left heart catheterization (LHC) with the intent to undergo PCI. Patients underwent rapid genetic testing using the Spartan RX assay, which defines CYP2C19 genetic status within 1 hour, allowing patients to be genotyped the same day of their LHC. Patients who were carriers of at least one LOF (*2 or *3) allele were randomized to receive either prasugrel [60mg loading dose (LD) - 10mg/day maintenance dose (MD)] or ticagrelor (180mg LD - 90mg b.i.d MD). Blood samples for PD analysis by VerifyNow were collected at 5 time points: baseline (prior to PCI), 30 minutes, 2 hours, 24 hours (or at hospital discharge whichever came first), and 1–4 weeks post-LD. All patients were treated with aspirin. The primary endpoint of our study was the non-inferiority in platelet reactivity, measured as PRU, at 24 hours of prasugrel vs ticagrelor in LOF allele carriers. Results A total of 781 consecutive patients scheduled for LHC were genotyped, of whom 223 (28.5%) were carriers of at least one LOF. Of these, 65 patients underwent PCI and randomized to prasugrel (n=32) vs ticagrelor (n=33). PRU levels at 24 hours were 33 vs 36 (prasugrel vs ticagrelor; mean difference = −3; 95% CI: −28 to 22; p=0.814) meeting the primary endpoint of non-inferiority. Both prasugrel and ticagrelor significantly reduced PRU to a similar extent with no differences between groups at all other time points (Figure). Accordingly, HPR rates were low and similar between groups. PRU by VerifyNow Conclusion Rapid genetic testing using the Spartan assay is feasible providing results in a timely fashion in a real-world clinical practice of patients undergoing PCI. Among patients with CYP2C19 LOF carrier status, prasugrel and ticagrelor are associated with similar levels of platelet inhibition. Acknowledgement/Funding Genetic testing was provided by Spartan RX

Background Patients with bicuspid aortic valve stenosis (BAV) were excluded from all the trileaflet aortic valve stenosis (TAV) pivotal trials, and therefore, their outcomes are not clearly defined. The aim of the study was to evaluate the outcomes of transcatheter aortic valve replacement (TAVR) in patients with BAV and compared them with those of TAV. Methods We evaluated the outcomes following TAVR of patients with BAV at our institution between April 2011 and November 2016 and compared them with the outcomes of patients with TAV treated with TAVR. The χ2 and the Mann-Whitney U tests were used to compare the groups, and a Kaplan-Meier analysis was performed to estimate long-term survival. Results TAVR was performed in a total of 567 patients, from which 50 (8.8%) had BAV and 517 (91.2%) had TAV. Patients with BAV were younger and had higher prevalence of chronic obstructive pulmonary disease, lower prevalence of coronary artery disease, higher body mass index, and lower Society of Thoracic Surgeons score (STS PROM). Patients with BAV had a slightly higher mean aortic valve gradient postoperatively (median 12 mm Hg [10-15] vs 10 [7-13], P mild 4.0% vs 3.5%, P = .541). Clinical outcomes were not different between the groups, including stroke (2.0% vs 1.5, P = .567) and the 30-day all-cause mortality (6.0% vs 1.5, P = .064). The 2-year survival (82.0% vs 83.4, P = .476) was similar between the groups. Conclusions This initial experience suggests that TAVR can be safely performed in patients with BAV, achieving similar short-term procedural and clinical outcomes when compared with patients with TAV.

The platelet inhibitory effects induced by oral P2YThis was a prospective, randomized, double-blind, placebo-controlled pharmacodynamic study conducted in patients undergoing primary percutaneous coronary intervention (n=50) who were randomized to treatment with either cangrelor or matching placebo (bolus followed by 2-hour infusion). All patients received ticagrelor 180-mg loading dose administered as crushed tablets at the time of cangrelor/placebo bolus administration. Pharmacodynamic analyses were performed at 8 time points. Pharmacodynamic effects were measured as P2YCompared with placebo, cangrelor was associated with reduced P2YIn patients undergoing primary percutaneous coronary intervention, cangrelor is an effective strategy to bridge the gap in platelet inhibition associated with the use of oral P2YURL: https://www.clinicaltrials.gov . Unique identifier: NCT03247738.

A systematic review was conducted to assess the efficacy of mitral valve repair using glutaraldehyde-treated autologous pericardial leaflet augmentation for rheumatic mitral regurgitation (MR). Five retrospective studies were identified, which included 196 patients with moderate or greater MR. There was 1 operative death (0.5%). At a mean follow-up of 3.2 ± 2.2 years, moderate or greater MR reoccurred in 22 patients (11.2%), reoperation was required in 9 (4.6%), and the cumulative survival was 98.9%. Finally, outcomes were similar between the patients who underwent augmentation of the anterior vs the posterior mitral leaflet. Pericardial leaflet augmentation is a viable technique for the treatment of rheumatic MR.

Objective An embolic ischemic stroke occurs in 10% to 40% of patients with valvular infective endocarditis (IE) and confers significant morbidity. The optimal timing of valve surgery in this population is not well defined. Methods With the use of PubMed, EMBASE, Ovid, and Cochrane databases, a systematic review identified 14 studies through October 2015 that compared early versus delayed surgery for valvular IE complicated by an ischemic stroke. Early surgery was defined as 3 days or less in one, 7 days or less in eight, and 14 days or less in five studies. Risk ratios (RRs) were calculated by the Mantel-Haenszel method under a fixed- or random-effects model, for the outcomes of perioperative stroke, operative mortality, and 1-year survival. Results A total of 833 patients (early surgery, 330; delayed surgery, 503) were included. The majority of operations were for aortic and/or mitral valve IE, with prosthetic valve IE present in 0% to 60%. Infection with Staphylococcus aureus ranged from 19% to 66%, and heart failure prevalence at the time of operation was 24% to 66%. Early surgery was associated with an increased risk of operative mortality (RR, 1.72; 95% confidence interval [CI], 1.27–2.34; P = 0.0005), which was significant regardless of surgery within the first 7 days (RR, 2.19; 95% CI, 1.45–3.31; P = 0.0002) or 14 days (RR, 1.72; 95% CI, 1.12–2.64; P = 0.01) after stroke. Surgical timing did not affect the risk of perioperative ischemic or hemorrhagic stroke or 1-year survival. Conclusions In patients with valvular IE complicated by ischemic stroke, early surgery is associated with an increased risk of operative mortality, with no observed benefit in 1-year survival.

The aim of this study was to evaluate the incidence and outcomes of surgical bailout during transcatheter aortic valve replacement (TAVR).The incidence and outcomes of unplanned conversion to open heart surgery, or "surgical bailout," during TAVR are not well characterized.Data from the Society of Thoracic Surgeons/American College of Cardiology TVT (Transcatheter Valve Therapy) Registry was analyzed with respect to whether surgical bailout was performed during the index TAVR procedure. A Cox proportional hazards models was used to evaluate 1-year mortality and major adverse cardiovascular events.Between November 2011 and September 2015, a total of 47,546 patients underwent TAVR. Surgical bailout during TAVR was performed in 1.17% of the cases (n = 558); the most frequent indications were valve dislodgement (22%), ventricular rupture (19.9%), and aortic valve annular rupture (14.2%). The incidence of surgical bailout significantly decreased over time (first tertile 1.25%, second tertile 1.43%, third tertile 1.04%; p = 0.0088). The 30-day and 1-year incidence of major adverse cardiovascular events (54.6% vs. 7.4% [p 0.0001] and 63.92% vs. 20.29% [p 0.0001]) and all-cause mortality (50.00% vs. 4.98% [p 0.0001] and 59.79% vs. 17.06% [p 0.0001]) were significantly higher in those who underwent bailout. Independent predictors of surgical bailout included female sex, hemoglobin, left ventricular ejection fraction, nonelective cases, and nonfemoral access. Body surface area was the only independent predictor of survival after surgical bailout.In a large, nationally representative registry, the need for surgical bailout in patients undergoing TAVR is low, and its incidence has decreased over time. However, surgical bailout after TAVR is associated with poor outcomes, including 50% mortality at 30 days.

Objectives To assess the treatment effect of TAVR versus SAVR on clinical outcomes to 3 years in patients stratified by chronic kidney disease (CKD) by retrospectively studying patients randomized to TAVR or SAVR. Background The impact of CKD on mid-term outcomes of patients undergoing TAVR versus SAVR is unclear. Methods Patients randomized to TAVR or SAVR in the CoreValve US Pivotal High Risk Trial were retrospectively stratified by eGFR: none/mild or moderate/severe CKD. To evaluate the impact of baseline CKD in TAVR patients only, all patients undergoing an attempted TAVR implant in the US Pivotal Trial and CAS were stratified by baseline eGFR into none/mild, moderate, and severe CKD. The primary endpoint was major adverse cardiovascular and renal events (MACRE), a composite of all-cause mortality, myocardial infarction, stroke/TIA, and new requirement of dialysis. Results Moderate/severe CKD was present in 62.7% and 60.7% of high-risk patients randomized to TAVR or SAVR, respectively. Baseline characteristics were similar between TAVR and SAVR patients in both CKD subgroups, except for higher rates of diabetes and higher serum creatinine in SAVR patients. Among high-risk patients with moderate/severe CKD, TAVR provided a lower 3-year MACRE rate compared with SAVR: 42.1% vs. 51.0, P = .04. Of 3,733 extreme- and high-risk TAVR patients, 39.9% had none/mild, 53.8% moderate, and 6.4% severe CKD. Worsening baseline CKD was associated with increased 3-year MACRE rates [none/mild 51.5%, moderate 54.5%, severe 63.1%, P = .001]. Conclusions TAVR results in lower 3-year MACRE versus SAVR in high-risk patients with moderate/severe CKD. In patients undergoing TAVR, worsening CKD increases mid-term mortality and MACRE. Randomized trials of TAVR vs. SAVR in patients with moderate-severe CKD would help elucidate the best treatment for these complex patients. Trial registration CoreValve US Pivotal Trial: NCT01240902. CoreValve Continued Access Study: NCT01531374.

Patent foramen ovale (PFO) is a cardiac anatomic structure frequently found in the general population, with an estimated prevalence of 25%–30%. PFO has been linked to increased risk for thromboembolism, including ischemic systemic and cerebrovascular events. The risk stems from the potential of paradoxical embolization of thrombi originating from the venous system through the anatomic patency onto the left-heart circulation. In fact, PFO has been found in up to 40%–50% of adult patients with stroke of unknown origin (cryptogenic) using transesophageal echocardiography and serves as an independent predictor of cryptogenic stroke. To decrease the risk of recurrent cerebrovascular events in this population, multiple treatment strategies, including medical therapy, device closure, and surgical repair, have been initiated and studied. Although data on the medical management of cryptogenic stroke in the setting of PFO are limited, the available evidence supports the notion that both aspirin (81–325 mg/day) and warfarin (international normalized ratio goal 2–3) decrease the risk of recurrent cryptogenic stroke in patients with PFO, with the latter potentially achieving lower recurrence rates. However, the preferred therapy, the ideal antiplatelet dosing, the duration of therapy, and the benefit of newer antiplatelet agents (P2Y12 inhibitors) are still unknown. Current guidelines denote that there is insufficient evidence to establish whether anticoagulation is superior or equivalent to aspirin. Nevertheless, the guidelines recommend at least antiplatelet therapy for patients with PFO and prior ischemic cerebrovascular events. A large body of literature supports the application of percutaneous devices for closure of PFO, as it decreases the incidence of recurrent stroke in patients with cryptogenic stroke. Two PFO closure devices, the Amplatzer PFO occluder and the GORE Cardioform, have shown a 45% and 76% risk reduction, respectively, in randomized controlled trials, compared with medical therapy alone. The Amplatzer PFO occluder is already US Food and Drug Administration approved for this indication (since 2016) and the GORE Cardioform closure device is expected to receive approval by the end of 2017. Accordingly, the guidelines stand to change in the near future to include PFO device closure in addition to standard medical therapy for the management of patients with cryptogenic stroke. Surgical closure of PFO appears to be a safe approach; nevertheless, conflicting data exist regarding the efficacy of elimination of an interatrial shunt, and a valid concern for recurrent cerebrovascular events remains. As no direct comparison is currently available between the three main management approaches, there are no clear advantages of surgery over medical therapy or over percutaneous device closure. Accordingly, a surgical approach should be considered as the last therapeutic option, limited to select patients who sustained cryptogenic stroke with a high risk of recurrent events in whom both device closure and medical therapy have failed or are contraindicated.

Systemic embolization from a primary cardiac tumor is a relatively frequent presentation. However, an acute myocardial infarction due to coronary embolization is rarely seen. We offer an unusual case of a 50-year-old man who presented with severe angina and was diagnosed with an inferolateral ST-segment-elevation myocardial infarction. Aside from otherwise healthy coronary arteries, his coronary angiogram revealed an acute occlusion of the first obtuse marginal branch, which was treated with balloon angioplasty. Because no residual plaque or dissection was found after the angioplasty, an embolic source was suspected. An echocardiogram then revealed a large mobile left atrial myxoma prolapsing into the left ventricle, so the patient underwent minimally invasive resection. Detailed pathologic examination of the myxoma revealed a concomitant high-grade B-cell lymphoma.

Background A staged approach of percutaneous coronary intervention (PCI) followed by minimally invasive valve surgery (MIVS) is an alternative to the conventional combined coronary artery bypass and valve surgery for patients with concomitant coronary artery and valve disease. Limited data exist on degree of the completeness of revascularization achieved with this approach and its impact on outcomes. Methods A total of 138 patients, who underwent a staged approach between January 2009 and June 2013, were retrospectively evaluated. Coronary angiograms were reviewed by two cardiologists blinded to outcomes and were then categorized into two groups: complete or incomplete revascularization, which was defined as ≥1 major epicardial coronary arteries of at least 2.0 mm diameter with ≥70% untreated obstruction after the index PCI and before MIVS. Results Complete and incomplete revascularization was achieved in 105 (76%) and 33 (24%) patients, respectively. The patients with incomplete revascularization had a lower ejection fraction, a higher STS score, and more prior myocardial infarctions and multi-vessel coronary artery disease. There were no differences in the post-operative complications, 30-day mortality, or 3-year survival (84 vs. 83%, P = 0.68). After a median follow-up of 29 months, incompletely revascularized patients had a higher incidence of acute coronary syndrome (2.9 vs. 12.9%, P = 0.05). Conclusions In patients undergoing a staged approach of PCI followed by MIVS, incomplete revascularization did not significantly impact the short or mid-term survival, but was associated with an increased incidence of acute coronary syndrome at follow-up. © 2015 Wiley Periodicals, Inc.