Clinical significance of residual ischaemia in acute myocardial infarction complicated by cardiogenic shock undergoing venoarterial-extracorporeal membrane oxygenation.

AIMS: Although culprit-only revascularization during the index procedure has been recommended in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS), the reduction in residual ischaemia is also emphasized to improve clinical outcomes. However, few data are available about the significance of residual ischaemia in patients undergoing mechanical circulatory supports. This study aimed to evaluate the effects of residual ischaemia on clinical outcomes in patients with AMI undergoing venoarterial-extracorporeal membrane oxygenation (VA-ECMO). METHODS AND RESULTS: Patients with AMI with multivessel disease who underwent VA-ECMO due to refractory CS were pooled from the RESCUE and SMC-ECMO registries. The included patients were classified into three groups according to residual ischaemia evaluated using the residual Synergy between percutaneous coronary intervention with Taxus and Cardiac Surgery (SYNTAX) score (rSS): rSS = 0, 0 < rSS ≤ 8, and rSS > 8. The primary outcome was 1-year all-cause death. A total of 408 patients were classified into the rSS = 0 (n = 100, 24.5%), 0 < rSS ≤ 8 (n = 136, 33.3%), and rSS > 8 (n = 172, 42.2%) groups. The cumulative incidence of the primary outcome differed significantly according to rSS (33.9 vs. 55.4 vs. 66.1% for rSS = 0, 0 < rSS ≤ 8, and rSS > 8, respectively, overall P < 0.001). In a multivariable model, rSS was independently associated with the risk of 1-year all-cause death (adjusted hazard ratio 1.03, 95% confidence interval 1.01-1.05, P = 0.003). Conversely, the baseline SYNTAX score was not associated with the risk of the primary outcome. Furthermore, when patients were stratified by rSS, the primary outcome did not differ significantly between the high and low delta SYNTAX score groups. CONCLUSION: In patients with AMI with refractory CS who underwent VA-ECMO, residual ischaemia was associated with an increased risk of 1-year mortality. Future studies are needed to evaluate the efficacy and safety of revascularization strategies to minimize residual ischaemia in patients with CS supported with VA-ECMO. CLINICAL TRIAL REGISTRATION: REtrospective and Prospective Observational Study to Investigate Clinical oUtcomes and Efficacy of Left Ventricular Assist Device for Korean Patients With Cardiogenic Shock (RESCUE), NCT02985008.

Impact of gender on mid-term prognosis of patients undergoing coronary artery bypass grafting.

OBJECTIVES: We evaluated the impact of sex on mid-term prognosis in patients who underwent coronary artery bypass grafting (CABG). Data on gender differences in current management or clinical outcomes after CABG are controversial, and there have been limited data focusing on them. METHODS: This was a retrospective and prospective, single-center, observational study. Between January 2001 and December 2017, 6613 patients who underwent CABG were enrolled from an institutional registry of Samsung Medical Center, Seoul, Korea (Clinicaltrials.gov, NCT03870815) and divided into two groups according to sex (female group, n = 1679 vs. male group, n = 4934). The primary outcome was cardiovascular death or myocardial infarction (MI) at 5 years. Propensity score matching analysis was performed to reduce confounding factors. RESULTS: During a mean follow-up duration of 54 months, a total of 252 cardiovascular death or MIs occurred (female, 78 [7.5%] vs. male, 174 [5.7%]). Multivariate analysis revealed no significant difference in the incidence of cardiovascular death or MI at 5 years between female and male groups (hazard ratio [HR] 1.05; 95% confidence interval [CI] 0.78 to 1.41; p = 0.735). After propensity score matching, the incidence of cardiovascular death or MI was still similar between the two groups (HR 1.08; 95% CI 0.76 to 1.54; p = 0.666). The similarity of long-term outcomes between the two groups was consistent across various subgroups. There was also no significant difference in the risk of 5-year cardiovascular death or MI between males and females according to age (pre- and postmenopausal status) (p for interaction = 0.437). CONCLUSIONS: After adjusting for baseline differences, sex does not appear to influence long-term risk of cardiovascular death or MI in patients undergoing CABG. CLINICAL TRIALS.GOV NUMBER: NCT03870815.

P2Y12 inhibitor monotherapy in complex percutaneous coronary intervention: A post-hoc analysis of SMART-CHOICE randomized clinical trial.

BACKGROUND: It remains unclear whether P2Y12 monotherapy, especially clopidogrel, following short-duration dual antiplatelet therapy (DAPT) is associated with favorable outcomes in patients undergoing complex percutaneous coronary intervention (PCI). Therefore, this study analyzed the efficacy and safety of P2Y12 inhibitor monotherapy, mostly clopidogrel (78%), in complex PCI following short-term DAPT. METHODS: The post-hoc analysis of the SMART-CHOICE trial involving 2,993 patients included 498 cases of complex PCIs, defined by at least one of the following features: 3 vessels treated, ≥ 3 stents implanted, ≥ 3 lesions treated, bifurcation with ≥ 2 stents implanted, and a total stent length of ≥ 60 mm. The primary endpoint was major adverse cardiac and cerebrovascular event (MACCE), defined as the composite of all-cause death, myocardial infarction, and stroke. The primary safety endpoint included bleeding, defined as Bleeding Academic Research Consortium (BARC) types 2 to 5. RESULTS: Complex PCI group had a higher risk of MACCE (4.0% vs. 2.3%, hazard ratio [HR] = 1.74, 95% confidence interval [CI]: 1.05-2.89, p = 0.033) and a similar risk of BARC types 2-5 bleeding (2.6% vs. 2.6%, HR = 1.02, 95% CI: 0.56-1.86, p = 0.939) compared with those without complex PCIs. Patients undergoing complex PCIs, followed by P2Y12 inhibitor monotherapy and 12 months of DAPT exhibited similar rates of MACCE (3.8% vs. 4.2%, HR = 0.92, 95% CI: 0.38-2.21, p = 0.853). CONCLUSIONS: P2Y12 inhibitor monotherapy, mostly clopidogrel, following 3 months of DAPT did not increase ischemic events in patients with complex PCIs.

Safety of 3-Month Dual Antiplatelet Therapy After Implantation of Ultrathin Sirolimus-Eluting Stents With Biodegradable Polymer (Orsiro): Results From the SMART-CHOICE Trial.

Background This study sought to investigate the safety of 3-month dual antiplatelet therapy (DAPT) in patients receiving ultrathin sirolimus-eluting stents with biodegradable polymer (Orsiro). Methods and Results The SMART-CHOICE (Smart Angioplasty Research Team: Comparison Between P2Y12 Antagonist Monotherapy vs Dual Anti- platelet Therapy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents) randomized trial compared 3-month DAPT followed by P2Y12 inhibitor monotherapy with 12-month DAPT in 2993 patients undergoing percutaneous coronary intervention. The present analysis was a prespecified subgroup analysis for patients receiving Orsiro stents. As a post hoc analysis, comparisons between Orsiro and everolimus-eluting stents were also done among patients receiving 3-month DAPT. Of 972 patients receiving Orsiro stents, 481 patients were randomly assigned to 3-month DAPT and 491 to 12-month DAPT. At 12 months, the target vessel failure, defined as a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization, occurred in 8 patients (1.7%) in the 3-month DAPT group and in 14 patients (2.9%) in the 12-month DAPT group (hazard ratio [HR], 0.58; 95% CI, 0.24-1.39; P=0.22). In whole population who were randomly assigned to receive 3-month DAPT (n=1495), there was no significant difference in the target vessel failure between the Orsiro group and the everolimus-eluting stent group (n=1014) (1.7% versus 1.8%; HR, 0.96; 95% CI, 0.41-2.22; P=0.92). Conclusions In patients receiving Orsiro stents, clinical outcomes at 1 year were similar between the 3-month DAPT followed by P2Y12 inhibitor monotherapy and 12-month DAPT strategies. With 3-month DAPT, there was no significant difference in target vessel failure between Orsiro and everolimus-eluting stents. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02079194.

Wirelessly controlled, bioresorbable drug delivery device with active valves that exploit electrochemically triggered crevice corrosion.

Implantable drug release platforms that offer wirelessly programmable control over pharmacokinetics have potential in advanced treatment protocols for hormone imbalances, malignant cancers, diabetic conditions, and others. We present a system with this type of functionality in which the constituent materials undergo complete bioresorption to eliminate device load from the patient after completing the final stage of the release process. Here, bioresorbable polyanhydride reservoirs store drugs in defined reservoirs without leakage until wirelessly triggered valve structures open to allow release. These valves operate through an electrochemical mechanism of geometrically accelerated corrosion induced by passage of electrical current from a wireless, bioresorbable power-harvesting unit. Evaluations in cell cultures demonstrate the efficacy of this technology for the treatment of cancerous tissues by release of the drug doxorubicin. Complete in vivo studies of platforms with multiple, independently controlled release events in live-animal models illustrate capabilities for control of blood glucose levels by timed delivery of insulin.

Effect of P2Y12 Inhibitor Monotherapy vs Dual Antiplatelet Therapy on Cardiovascular Events in Patients Undergoing Percutaneous Coronary Intervention: The SMART-CHOICE Randomized Clinical Trial.

Importance: Data on P2Y12 inhibitor monotherapy after short-duration dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention are limited. Objective: To determine whether P2Y12 inhibitor monotherapy after 3 months of DAPT is noninferior to 12 months of DAPT in patients undergoing PCI. Design, Setting, and Participants: The SMART-CHOICE trial was an open-label, noninferiority, randomized study that was conducted in 33 hospitals in Korea and included 2993 patients undergoing PCI with drug-eluting stents. Enrollment began March 18, 2014, and follow-up was completed July 19, 2018. Interventions: Patients were randomly assigned to receive aspirin plus a P2Y12 inhibitor for 3 months and thereafter P2Y12 inhibitor alone (n = 1495) or DAPT for 12 months (n = 1498). Main Outcomes and Measures: The primary end point was major adverse cardiac and cerebrovascular events (a composite of all-cause death, myocardial infarction, or stroke) at 12 months after the index procedure. Secondary end points included the components of the primary end point and bleeding defined as Bleeding Academic Research Consortium type 2 to 5. The noninferiority margin was 1.8%. Results: Among 2993 patients who were randomized (mean age, 64 years; 795 women [26.6%]), 2912 (97.3%) completed the trial. Adherence to the study protocol was 79.3% of the P2Y12 inhibitor monotherapy group and 95.2% of the DAPT group. At 12 months, major adverse cardiac and cerebrovascular events occurred in 42 patients in the P2Y12 inhibitor monotherapy group and in 36 patients in the DAPT group (2.9% vs 2.5%; difference, 0.4% [1-sided 95% CI, -∞% to 1.3%]; P = .007 for noninferiority). There were no significant differences in all-cause death (21 [1.4%] vs 18 [1.2%]; hazard ratio [HR], 1.18; 95% CI, 0.63-2.21; P = .61), myocardial infarction (11 [0.8%] vs 17 [1.2%]; HR, 0.66; 95% CI, 0.31-1.40; P = .28), or stroke (11 [0.8%] vs 5 [0.3%]; HR, 2.23; 95% CI, 0.78-6.43; P = .14) between the 2 groups. The rate of bleeding was significantly lower in the P2Y12 inhibitor monotherapy group than in the DAPT group (2.0% vs 3.4%; HR, 0.58; 95% CI, 0.36-0.92; P = .02). Conclusions and Relevance: Among patients undergoing percutaneous coronary intervention, P2Y12 inhibitor monotherapy after 3 months of DAPT compared with prolonged DAPT resulted in noninferior rates of major adverse cardiac and cerebrovascular events. Because of limitations in the study population and adherence, further research is needed in other populations. Trial Registration: ClinicalTrials.gov Identifier: NCT02079194.

Second-generation drug-eluting stenting versus coronary artery bypass grafting for treatment of coronary chronic total occlusion.

BACKGROUND: Limited data are available regarding the long-term clinical outcomes of percutaneous coronary intervention (PCI) using second-generation drug-eluting stents (DESs) versus coronary artery bypass grafting (CABG) for the treatment of coronary artery disease (CAD) with chronic total occlusion (CTO). We compared the clinical outcomes of patients with multivessel CAD including CTO lesions treated with PCI using DESs versus CABG. METHODS: We analyzed data from 423 consecutive patients who underwent successful revascularization for CTO between March 2008 and February 2012. Death or myocardial infarction (MI) and major adverse cardiac and cerebrovascular events (MACCE) were compared between patients treated with PCI using second-generation DESs (n=232, 2nd DES group) versus those treated with CABG (n=191, CABG group). To reduce selection bias according to treatment strategy and other potential confounding factors, inverse probability of treatment weighting (IPTW) was also performed. RESULTS: During a median follow-up duration of 32 months, there was no significant difference in death or MI [hazard ratio (HR): 0.69; 95% confidence interval (CI): 0.29-1.63; p=0.399] or MACCE (HR: 1.32; 95% CI: 0.74-2.35; p=0.341) between the 2nd DES group and the CABG group based on multivariable analysis. After IPTW adjustment, the incidences of death or MI (HR: 0.72; 95% CI: 0.26-1.95; p=0.518) and MACCE (HR: 1.49; 95% CI: 0.76-2.91; p=0.244) remained similar in the two groups. In subgroup analysis, the effect of second-generation drug-eluting stenting was comparable to that of CABG across various subgroups without a significant p-value for the interaction. CONCLUSIONS: The efficacy of PCI using second-generation DES was comparable to that of CABG in CTO patients with multivessel CAD.

Cardioprotective Effects of Intracoronary Morphine in ST-Segment Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention: A Prospective, Randomized Trial.

BACKGROUND: A cardioprotective role of morphine acting via opioid receptors has been demonstrated, and previous preclinical studies have reported that morphine could reduce reperfusion injury and myocardial infarct size in a way similar to that of ischemic periconditioning. This study aimed to evaluate the effect of intracoronary morphine on myocardial infarct size in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. METHODS AND RESULTS: This study was designed as a 2-center, prospective, randomized, open-label, blinded end point trial. A total of 91 ST-elevation myocardial infarction patients with thrombolysis in myocardial infarction flow grade of 0 to 1 undergoing primary percutaneous coronary intervention were randomly assigned to a morphine or control group at a 1:1 ratio. The morphine group received 3 mg of morphine sulfate diluted with 3 mL of normal saline, and the control group received 3 mL of normal saline into a coronary artery immediately after restoration of coronary flow. The primary end point was myocardial infarct size assessed by cardiac magnetic resonance imaging The cardiac magnetic resonance images were evaluated for 42 and 38 patients in the morphine and control groups, respectively. Myocardial infarct size was not different between the 2 groups (25.6±11.2% versus 24.6±10.5%, P=0.77), nor was the extent of microvascular obstruction or myocardial salvage index (6.0±6.3% versus 5.1±4.6%, P=0.91; 31.1±15.2% versus 30.3±10.9%, P=0.75, respectively). There was no difference in peak creatine kinase-MB level, final thrombolysis in myocardial infarction flow, myocardial brush grade, or complete resolution of ST-segment. CONCLUSIONS: Intracoronary morphine administration could not reduce myocardial infarct size in ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01738100.

Clinical implications of residual SYNTAX score after percutaneous coronary intervention in patients with chronic total occlusion and multivessel coronary artery disease: a comparison with coronary artery bypass grafting.

AIMS: In this study we sought to evaluate the clinical impact of the residual SYNTAX score (rSS) after percutaneous coronary intervention (PCI) in patients with chronic total occlusion (CTO) and multivessel coronary artery disease (CAD). METHODS AND RESULTS: We analysed data from 1,043 patients with CTO and multivessel CAD who were treated with PCI or coronary artery bypass grafting (CABG). Patients were divided into three groups: patients with rSS≤12 after PCI (rSS≤12 group, n=445), patients with rSS>12 after PCI (rSS>12 group, n=150), and patients who underwent CABG (CABG group, n=448). We compared the incidence of cardiac death among the three groups. During a median follow-up period of 42 months, cardiac death occurred in 14 patients (3.1%) in the rSS≤12 group, 14 patients (9.3%) in the rSS>12 group, and 29 patients (6.5%) in the CABG group. On multivariate analysis, the rSS≤12 group had a significantly lower incidence of cardiac death than the rSS>12 group (hazard ratio [HR] 0.35, 95% confidence interval [CI]: 0.16 to 0.75; p=0.01), but had an incidence of cardiac death similar to that of the CABG group (HR 0.63, 95% CI: 0.32 to 1.23; p=0.17). CONCLUSIONS: An rSS≤12 after PCI may reduce the risk of cardiac mortality and could be a measure of reasonable incomplete revascularisation in patients with CTO and multivessel CAD.

Association of ß-blocker therapy with long-term clinical outcomes in patients with coronary chronic total occlusion.

There are limited data regarding the efficacy of ß-blockers for secondary prevention in patients with coronary chronic total occlusion (CTO). Therefore, we investigated the association of ß-blocker therapy with long-term clinical outcomes in CTO patients. From March 2003 to February 2012, a total of 2024 CTO patients treated with either medical therapy alone or revascularization were enrolled in the study. We assessed 1596 patients with stable ischemic heart disease and divided them into the ß-blocker group (n = 932) and the no-ß-blocker group (n = 664). The primary outcome was all-cause death. The median follow-up duration was 3.9 (interquartile range: 2.0-6.2) years. All-cause death occurred in 11.6% patients in the ß-blocker group and 13.6% patients in the no-ß-blocker group (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.61-1.08; P = 0.15). In the propensity score-matched population (570 pairs), all-cause death occurred in 12.3% patients in the ß-blocker group and 12.8% patients in the no-ß-blocker group (HR: 0.93, 95% CI: 0.67-1.29; P = 0.66). In subgroup analysis, ß-blocker therapy was associated with better outcome, in terms of all-cause death, in patients with CTO of the left anterior descending coronary artery and Synergy Between PCI with Taxus and Cardiac Surgery (SYNTAX) score ≥23 (P for interaction = 0.01 and 0.02, respectively). In conclusion, ß-blocker therapy was not associated with favorable long-term clinical outcomes in stable CTO patients, regardless of treatment strategy. However, ß-blocker therapy might be beneficial in a highly selective group of CTO patients with a high ischemic burden.

Clinical outcomes of multiple chronic total occlusions in coronary arteries according to three therapeutic strategies: Bypass surgery, percutaneous intervention and medication.

BACKGROUND: Limited data exist regarding clinical outcomes of multiple chronic total occlusions (CTOs) according to therapeutic strategies, coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), and medical treatment (MT). METHODS: From March 2003 to February 2012, a total of 2024 patients with at least one CTO were enrolled in retrospective, single-center registry. 393 patients with at least two CTOs were categorized based on the intention-to-treat principle. Propensity-score matching was performed. The primary outcome was major adverse cardiac and cerebral events (MACCE). RESULTS: Of 393 patients with multiple CTOs, 169 patients (43%) were referred for CABG, 130 (33%) for PCI, and 94 (24%) for MT. Median overall follow-up duration was 46.5 (interquartile range 22.7 to 74.6) months. After propensity-score matching analysis, CABG had lower rates of MACCE when compared with PCI (HR=0.43, 0.21-0.85, P=0.01) and MT (HR=0.10, 0.04-0.27, P<0.01). Rates of repeat revascularization was significantly lower in CABG, compared with PCI (HR=0.05, 0.01-0.40, P<0.01) and MT (HR=0.01, 0.00-0.54, P=0.02). CABG had similar rates of cardiac death compared with PCI group (HR=0.97, 0.37-2.53, P=0.95), but had significantly lower rates of cardiac death compared with MT (HR=0.24, 0.08-0.75, P=0.01). CONCLUSIONS: For management of multiple CTOs, MT alone was associated with higher incidence of cardiac death and MACCE compared with CABG. PCI was associated with higher incidence of MACCE, as driven by higher repeat revascularization rate. These findings suggest that CABG might be associated with better clinical outcome and considered as the preferred treatment strategy in patients with multiple CTOs.

Long-term survival benefit of revascularization compared with medical therapy in patients with coronary chronic total occlusion and well-developed collateral circulation.

OBJECTIVES: The purpose of this study was to compare the long-term clinical outcomes of patients with chronic total occlusion (CTO) and well-developed collateral circulation treated with revascularization versus medical therapy. BACKGROUND: Little is known about the clinical outcomes and optimal treatment strategies of CTO with well-developed collateral circulation. METHODS: We screened 2,024 consecutive patients with at least 1 CTO detected on coronary angiogram. Of these, we analyzed data from 738 patients with Rentrop 3 grade collateral circulation who were treated with medical therapy alone (n = 236), coronary artery bypass grafting (n = 170) or percutaneous coronary intervention (n = 332; 80.1% successful). Patients who underwent revascularization and medical therapy (revascularization group, n = 502) were compared with those who underwent medical therapy alone (medication group, n = 236) in terms of cardiac death and major adverse cardiac events (MACE), defined as the composite of cardiac death, myocardial infarction, and repeat revascularization. RESULTS: During a median follow-up duration of 42 months, multivariate analysis revealed a significantly lower incidence of cardiac death (hazard ratio [HR]: 0.29; 95% confidence interval [CI]: 0.15 to 0.58; p < 0.01) and MACE (HR: 0.32; 95% CI: 0.21 to 0.49; p < 0.01) in the revascularization group compared with the medication group. After propensity score matching, the incidence of cardiac death (HR: 0.27; 95% CI: 0.09 to 0.80; p = 0.02) and MACE (HR: 0.44; 95% CI: 0.23 to 0.82; p = 0.01) were still significantly lower in the revascularization group than in the medication group. CONCLUSIONS: In patients with coronary CTO and well-developed collateral circulation, aggressive revascularization may reduce the risk of cardiac mortality and MACE.

Laterally spreading tumors of the colorectum: clinicopathologic features and malignant potential by macroscopic morphology.

BACKGROUND/AIMS: Laterally spreading tumors (LSTs) are being increasingly reported nowadays. The aims of this study were to analyze the clinicopathologic characteristics and to identify the risk factors of malignancy in patients with LSTs by morphological subclassification. PATIENTS AND METHODS: The authors retrospectively reviewed 326 LSTs (287 patients). Patient characteristics, endoscopic findings, and histologic findings were analyzed. Endoscopic findings were subdivided into homogeneous, mixed nodular, flat elevated, and pseudo-depressed subtypes. The clinicopathological features of these subtypes were compared. RESULTS: Of the 287 patients treated, 173 (50.3 %) were male and overall mean patient age was 65 ± 10 years (ranged 35 to 83 year). Of the 326 LSTs diagnosed, 116 (35.6 %) were homogeneous and 102 (31.3 %) were flat elevated subtype. The location was significantly different among morphological subtype. Tumors of the mixed nodular subtype were significantly larger than the tumors of the other three subtypes (p = 0.00). Of the 326 lesions, 279 underwent endoscopic mucosal resection (granular type 88.1 % (177/201)/nongranular type 81.6 % (102/125)). Two hundred forty-nine lesions (76.4 %) were resected en bloc, and 45 lesions (13.8 %) were resected using the piecemeal technique. Piecemeal resection was significantly more common for the pseudo-depressed subtype (27.0 %, p = 0.00). The overall malignancy rate on a lesion basis was 8.6 %. The malignancy rate increased with lesion size and was higher for the pseudo-depressed (24.3 %) and the mixed nodular subtype (14.1 %). Submucosal invasion was noted for 16 % of pseudo-depressed lesions, and this was significantly higher than the invasion rates of the other subtypes (p = 0.06). By multivariate analysis, morphologic subtype, especially the pseudo-depressed or mixed nodular subtype and size larger than 20 mm were risk factor of malignancy. CONCLUSIONS: The clinicopathological features of laterally spreading tumors differ with respect to macroscopic morphology, and the risk of malignant transformation is significantly higher for the mixed nodular or pseudo-depressed subtypes and lesion larger than 20 mm. Careful consideration is required when choosing a treatment modality, and lesions of the mixed nodular and pseudo-depressed subtypes should be completely removed.