P2Y12 Inhibition in Patients Requiring Oral Anticoagulation After Percutaneous Coronary Intervention: The SWAP-AC-2 Study.

BACKGROUND: Among patients treated with a novel oral anticoagulant (NOAC) undergoing percutaneous coronary intervention (PCI), combination therapy with clopidogrel (ie, known as dual antithrombotic therapy [DAT]) is the treatment of choice. However, there are concerns for individuals with impaired response to clopidogrel. OBJECTIVES: The authors sought to assess the pharmacodynamic (PD) effects of clopidogrel vs low-dose ticagrelor in patients with impaired clopidogrel response assessed by the ABCD-GENE score. METHODS: This was a prospective, randomized PD study of NOAC-treated patients undergoing PCI. Patients with an ABCD-GENE score ≥10 (n = 39), defined as having impaired clopidogrel response, were randomized to low-dose ticagrelor (n = 20; 60 mg twice a day) or clopidogrel (n = 19; 75 mg once a day). Patients with an ABCD-GENE score <10 (n = 42) were treated with clopidogrel (75 mg once a day; control cohort). PD assessments at baseline and 30 days post-randomization (trough and peak) were performed to assess P2Y12 signaling (VerifyNow P2Y12 reaction units [PRU], light transmittance aggregometry, and vasodilator-stimulated phosphoprotein); makers of thrombosis not specific to P2Y12 signaling were also assessed. The primary endpoint was PRU (trough levels) at 30 days. RESULTS: At 30 days, PRU levels were reduced with ticagrelor-based DAT compared with clopidogrel-based DAT at trough (23.0 [Q1-Q3: 3.0-46.0] vs 154.5 [Q1-Q3: 77.5-183.0]; P < 0.001) and peak (6.0 [Q1-Q3: 4.0-14.0] vs 129.0 [Q1-Q3: 66.0-171.0]; P < 0.001). Trough PRU levels in the control arm (104.0 [Q1-Q3: 35.0-167.0]) were higher than ticagrelor-based DAT (P = 0.005) and numerically lower than clopidogrel-based DAT (P = 0.234). Results were consistent by light transmittance aggregometry and vasodilator-stimulated phosphoprotein. Markers measuring other pathways leading to thrombus formation were largely unaffected. CONCLUSIONS: In NOAC-treated patients undergoing PCI with an ABCD-GENE score ≥10, ticagrelor-based DAT using a 60-mg, twice-a-day regimen reduced platelet P2Y12 reactivity compared with clopidogrel-based DAT. (Tailoring P2Y12 Inhibiting Therapy in Patients Requiring Oral Anticoagulation After PCI [SWAP-AC-2]; NCT04483583).

Switching from Dual Antiplatelet Therapy with Aspirin Plus a P2Y12 Inhibitor to Dual Pathway Inhibition with Aspirin Plus Vascular-Dose Rivaroxaban: The Switching Anti-Platelet and Anti-Coagulant Therapy (SWAP-AC) Study.

BACKGROUND: To date, there are 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 (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 (TF), and a combination of collagen, ADP, and TF (maximum platelet aggregation %); thrombin generation (TG). Assays were performed at baseline and 30 days postrandomization. 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. CLINICAL TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov Unique Identifier: NCT04006288.

Switching From Cangrelor to Prasugrel in Patients Undergoing Percutaneous Coronary Intervention: The Switching Antiplatelet-6 (SWAP-6) Study.

BACKGROUND: A drug-drug interaction (DDI) may occur when transitioning from intravenous P2Y12 inhibition with cangrelor to oral P2Y12 inhibition with prasugrel. However, this has never been tested in patients undergoing percutaneous coronary intervention (PCI). OBJECTIVES: This study sought to rule out a DDI when cangrelor and prasugrel are concomitantly administered in PCI patients. METHODS: SWAP-6 (Switching Antiplatelet-6) was a prospective, randomized, 3-arm, open-label pharmacokinetic (PK) and pharmacodynamic (PD) study. Patients (N = 77) were randomized to 1) prasugrel only at the start of PCI, 2) cangrelor plus prasugrel concomitantly at the start of PCI, or 3) cangrelor at the start of PCI plus prasugrel at the end of infusion. Cangrelor infusion was maintained for 2 hours. PK/PD assessments were performed at baseline and 6 time points postrandomization. The primary endpoint was noninferiority in VerifyNow (Werfen) P2Y12 reaction units measured at 4 hours after randomization between cangrelor plus prasugrel concomitantly administered vs prasugrel only. PK assessments included plasma levels of the active metabolite of prasugrel. RESULTS: Compared with prasugrel, cangrelor further enhances P2Y12 inhibitory effects. At 4 hours postrandomization, P2Y12 reaction unit levels were significantly lower with prasugrel only compared to cangrelor and prasugrel concomitantly administered (least squares means difference = 130; 95% CI: 85-176), failing to meet the prespecified noninferiority margin. Findings were corroborated by multiple PD assays. The active metabolite of prasugrel levels were not affected by concomitant administration of cangrelor and were low at the end of cangrelor infusion. CONCLUSIONS: In patients undergoing PCI, concomitant administration of prasugrel with cangrelor leads to a marked increase in platelet reactivity after stopping cangrelor infusion, supporting the presence of a DDI. (Switching Antiplatelet Therapy-6 [SWAP-6]; NCT04668144).

Cangrelor in Patients With Coronary Artery Disease Pretreated With Ticagrelor: The Switching Antiplatelet (SWAP)-5 Study.

BACKGROUND: There are no studies specifically designed to rule out a drug-drug interaction (DDI) when cangrelor is used among patients who have been pretreated with ticagrelor. OBJECTIVES: This study sought to rule out a DDI among cangrelor-treated patients who have been pretreated with ticagrelor. METHODS: In this prospective, randomized, double-blind, placebo-controlled, crossover, pharmacokinetic (PK) and pharmacodynamic (PD) study, patients with coronary artery disease (N = 20) were pretreated with a 180-mg ticagrelor loading dose and after 1 hour randomized to placebo or cangrelor (bolus and infusion for 2 hours). Patients crossed over after 1 to 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, vasodilator-stimulated phosphoprotein, and Total Thrombus-Formation Analysis System. PK/PD assessments were performed at 7 time points. RESULTS: Compared with placebo, adding cangrelor to patients pretreated with ticagrelor resulted in a significant reduction in PRU at 30 minutes and 1 hour after starting infusion. At 2 hours after stopping cangrelor/placebo infusion, PRU were low and similar in both groups (16.9 vs 12.6; mean difference: 4.3; 95% CI: -28.6 to 37.3), meeting the noninferiority primary endpoint (predefined noninferiority 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 pretreated 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. (PD and PK Profiles of Switching Between Cangrelor and Ticagrelor Following Ticagrelor Pre-treatment [SWAP-5]; NCT04634162).

Platelet P2Y12 inhibiting therapy in adjunct to vascular dose of rivaroxaban or aspirin: a pharmacodynamic study of dual pathway inhibition vs. dual antiplatelet therapy.

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.

Pharmacodynamic Profiles of Dual-Pathway Inhibition with or without Clopidogrel versus Dual Antiplatelet Therapy in Patients with Atherosclerotic Disease.

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.

Pharmacodynamic Effects of Vorapaxar in Prior Myocardial Infarction Patients Treated With Potent Oral P2Y12 Receptor Inhibitors With and Without Aspirin: Results of the VORA-PRATIC Study.

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 P2Y12 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 P2Y12 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<0.001; primary end point). This effect was attenuated but still significant in the absence of aspirin (dual therapy versus DAPT at 30 days: mean difference=-15; 95% CI,-23 to -7; P<0.001; between-group comparisons, P<0.05). Vorapaxar abolished TRAP-induced aggregation (P<0.001), without affecting thrombin generation and clot strength. There were no differences in markers of P2Y12 reactivity. Markers sensitive to aspirin-induced effects increased (P<0.001) in the dual-therapy arm. Conclusions In post-myocardial infarction patients treated with potent P2Y12 inhibitors, vorapaxar reduces platelet-driven global thrombogenicity, an effect that persisted, albeit attenuated, in the absence of aspirin and without affecting markers of P2Y12 reactivity or clot kinetics. The clinical implications of these PD observations warrant future investigation. Registration URL: https://www.clini​caltr​ials.gov. Unique identifier: NCT02545933.

Incidence and Outcomes of Surgical Bailout During TAVR: Insights From the STS/ACC TVT Registry.

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 < 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. 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.

Trends and Outcomes of Alternative-Access Transcatheter Aortic Valve Replacement.

BACKGROUND: Alternative access (AA) is still required for a significant proportion of patients undergoing transcatheter aortic valve replacement (TAVR). We sought to compare the clinical outcomes of patients undergoing AA vs transfemoral (TF) access. METHODS: We retrospectively evaluated the outcomes of patients undergoing AA-TAVR between April 2011 and November 2016, and compared them with those who had TF-TAVR. Chi-square and Mann-Whitney U-tests were used to compare the groups and Kaplan-Meier analysis was performed to estimate long-term survival. RESULTS: TAVR was performed in a total of 600 patients, of which 78 (13%) had AA and 522 (87%) had TF access. Patients undergoing AA were younger, and had higher prevalence of chronic obstructive pulmonary disease, peripheral vascular disease, prior myocardial infarction, and prior sternotomy. Greater than mild paravalvular regurgitation (4.2% vs 0.0%; P=.04) and unplanned vascular surgery (5.4% vs 1.3%; P=.09) were more frequent in the TF group. However, patients who underwent AA had longer hospital stay (median 4 days [interquartile range, 3-7 days] vs 3 days [interquartile range, 3-4 days]; P<.001) and an increased incidence of prolonged ventilation (5.1% vs 1.3%; P=.06), 30-day all-cause (5.1% vs 1.7%; P=.08), and cardiovascular mortality (5.1% vs 1.3%; P=.04). The 6-month (15.7% vs 5.7%; P<.01) and 12-month (16.7% vs 10.2%; P=.07) mortality rates were higher for patients undergoing AA. The usage of AA significantly decreased over time (P=.01), primarily driven by a decrease in transapical (P<.001) and direct aortic access (P=.02). CONCLUSIONS: AA-TAVR is associated with an increased incidence of postoperative adverse events, including mortality, when compared with those undergoing TF access.

Platelet Inhibition With Cangrelor and Crushed Ticagrelor in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

BACKGROUND: The platelet inhibitory effects induced by oral P2Y12 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 P2Y12 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 P2Y12 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 P2Y12 reaction units by VerifyNow and platelet reactivity index by vasodilator-stimulated phosphoprotein. RESULTS: Compared with placebo, cangrelor was associated with reduced P2Y12 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<0·001; primary end point). Parallel findings were shown with platelet reactivity index. Accordingly, high on-treatment platelet reactivity rates were reduced with cangrelor. After discontinuation of cangrelor/placebo infusion, there were no differences in levels of platelet reactivity between groups, ruling out a drug-drug interaction when cangrelor and ticagrelor are concomitantly administered. 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 P2Y12 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.

Pharmacodynamic Effects of Vorapaxar in Patients With and Without Diabetes Mellitus: Results of the OPTIMUS-5 Study.

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).

A Staged Approach of Proximal Left Anterior Descending Coronary Artery Percutaneous Intervention Followed by Minimally Invasive Valve Surgery.

BACKGROUND AND AIM OF THE STUDY: A subset of patients requiring coronary revascularization of the proximal left anterior descending coronary artery (LAD) and valve surgery may benefit from a staged approach, rather than combined median sternotomy coronary artery bypass graft (CABG) and valve surgery. METHODS: A retrospective evaluation was made of the outcomes of patients with significant proximal LAD and valvular heart disease undergoing a staged approach of percutaneous coronary intervention (PCI) followed by minimally invasive valve surgery (MIVS) at the authors' institution between February 2009 and April 2014. A Kaplan-Meier analysis was performed to estimate mid-term survival. RESULTS: A total of 68 consecutive patients (mean age 75.2 ± 8.9 years) was identified. PCI was performed for one- or two-vessel disease in 76.5% and 23.5% of the patients, respectively. Within a median of 39 days (IQR 11-62 days), 91.2% of patients underwent primary MIVS, and 8.8% underwent re-operative MIVS, of which 58 (85.3%) were single-valve and 10 (14.7%) were double-valve operations. At the time of surgery, 72.1% of the patients were receiving dual anti-platelet therapy. The 30-day mortality was 2.9%. At a mean follow up of 26 ± 16 months, 7.4% of the patients had a non-target vessel acute coronary syndrome, and the survival rate was 88.2%. CONCLUSIONS: Among a select group of patients with proximal LAD and valvular disease, a staged approach of PCI followed by MIVS can be safely performed for primary or re-operative surgery, with excellent mid-term outcomes.

Staged percutaneous coronary intervention followed by minimally invasive mitral valve surgery versus combined coronary artery bypass graft and mitral valve surgery for two-vessel coronary artery disease and moderate to severe ischemic mitral regurgitation.

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.

Hybrid approach of percutaneous coronary intervention followed by minimally invasive mitral valve surgery: a 5-year single-center experience.

BACKGROUND: The current study evaluated the safety and feasibility of staged ("hybrid") percutaneous coronary intervention (PCI) followed by isolated minimally invasive mitral valve (MV) surgery [PCI + minimally invasive mitral valve surgery (MIMVS)], for patients with concomitant coronary artery and MV disease. METHODS: A total of 93 patients who underwent PCI + MIMVS for coronary artery and MV disease between February 2009 and April 2014 were retrospectively analyzed. RESULTS: There were 54 (58.1%) men and 39 (41.9%) women. The mean age was 73±8 years, and all patients had severe mitral regurgitation. PCI was performed for single-vessel coronary artery disease in 40 (43%) patients, two-vessel in 49 (52.7%), and three-vessel in 4 (4.3%). Within a median of 48 days (IQR, 18-71) after PCI, 78 (83.9%) patients underwent primary valve surgery, and 15 (16.1%) underwent re-operative valve surgery, with 56 (60.2%) having MV replacement, and 37 (39.8%) having MV repair. Sixty-five (69.9%) patients were being treated with dual anti-platelet therapy at the time of surgery. The median number of transfused intra-operative red blood cell units was 1 (IQR, 0-2), and the intensive care unit and hospital lengths of stay were 46 hours (IQR, 27-76) and 8 days (IQR, 5-11), respectively. Post-operatively, there was 1 (1.1%) cerebrovascular accident, 2 (2.2%) patients developed acute kidney injury, and 4 (4.3%) required a re-operation for bleeding. Thirty-day mortality occurred in 4 (4.3%) patients. At a mean follow-up of 15.3±13.2 months, 3 (3.4%) patients required target-vessel revascularization. The survival rate was 89% and 85% at 1 and 3 years, respectively. CONCLUSIONS: In patients with concomitant coronary artery and MV disease, PCI + MIMVS can be safely performed and is associated with good short-term and follow-up outcomes.

Outcomes of a Combined Approach of Percutaneous Coronary Revascularization and Cardiac Valve Surgery.

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.

Coronary Artery Disease Complexity on the Outcomes of a Staged Approach of PCI Followed by Minimally Invasive Valve Surgery.

OBJECTIVE: A 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. METHODS: We 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). RESULTS: There 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%). CONCLUSIONS: A 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.

Anterior Mitral Leaflet Augmentation for Ischemic Mitral Regurgitation Performed Via a Right Thoracotomy Approach.

Ischemic mitral regurgitation (MR) after myocardial infarction is associated with poor long-term survival, and the optimal treatment strategy remains debated. The most common repair technique used is a restrictive annuloplasty. However, up to 15% to 30% of patients experience recurrent MR owing to progressive left ventricular remodeling and geometric distortion of the mitral valve apparatus. Anterior mitral leaflet augmentation using a pericardial patch, in combination with a true-sized mitral annuloplasty, has been proposed as an adjunctive technique to increase the durability of valve repair for ischemic MR. Herein, we describe 2 cases of anterior mitral leaflet augmentation with annuloplasty repair for severe ischemic MR via a minimally invasive right thoracotomy, and review the literature regarding patient selection and clinical outcomes of this technique.

A Meta-Analysis of Early Versus Delayed Surgery for Valvular Infective Endocarditis Complicated by Embolic Ischemic Stroke.

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.

A Systematic Review of Mitral Valve Repair With Autologous Pericardial Leaflet Augmentation for Rheumatic Mitral Regurgitation.

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.