BACKGROUND: Although venoarterial extracorporeal membrane oxygenation (VA-ECMO) is beneficial for the treatment of profound cardiogenic shock, peripheral VA-ECMO cannulation can increase left ventricular afterload, thus compromising myocardial recovery. We investigated whether early routine left ventricular unloading can reduce 30-day mortality compared with the conventional approach in patients with cardiogenic shock undergoing VA-ECMO. METHODS: This randomized clinical trial involved 116 patients with cardiogenic shock undergoing VA-ECMO from March 2021 to September 2022 at Chonnam National University Hospital, Gwangju, South Korea. The patients were randomly assigned to undergo either early routine left ventricular unloading with transseptal left atrial cannulation within 12 hours after randomization (n=58) or the conventional approach, which permitted rescue transseptal left atrial cannulation in case of an increased left ventricular afterload (n=58). The primary outcome was all-cause mortality within 30 days. RESULTS: All 116 randomized patients (mean age, 67.6±13.5 years; 34 [29.3%] women) completed the trial. At 30 days, all-cause death had occurred in 27 (46.6%) patients in the early group and 26 (44.8%) patients in the conventional group (hazard ratio, 1.02 [95% CI, 0.59–1.74]; P =0.942). Crossover to rescue transseptal left atrial cannulation occurred in 29 patients (50%) in the conventional group according to a clear indication. Time to rescue transseptal cannulation in the conventional group was a median of 21.8 (interquartile range, 12.4–52.2) hours after randomization. There were no significant differences in other secondary outcomes between the 2 groups except for a shorter time to disappearance of pulmonary congestion in the early group (median, 3 [interquartile range, 2–6] versus 5 [interquartile range, 3–7] days; P =0.027). CONCLUSIONS: Among patients with cardiogenic shock undergoing VA-ECMO, early routine left ventricular unloading with transseptal left atrial cannulation did not reduce 30-day mortality compared with the conventional strategy, which permitted rescue transseptal left atrial cannulation. These findings should be cautiously interpreted until the results of multicenter trials using other unloading modalities become available. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04775472.

Background: In the absence of obstructive coronary stenoses, abnormality of noninvasive stress tests (NIT) in patients with chronic coronary syndromes may indicate myocardial ischemia of nonobstructive coronary arteries (INOCA). The differential prognosis of INOCA according to the presence of coronary microvascular dysfunction (CMD) and incremental prognostic value of CMD with intracoronary physiologic assessment on top of NIT information remains unknown. Methods and Results: From the international multicenter registry of intracoronary physiologic assessment (ILIAS [Inclusive Invasive Physiological Assessment in Angina Syndromes] registry, N=2322), stable patients with NIT and nonobstructive coronary stenoses with fractional flow reserve >0.80 were selected. INOCA was diagnosed when patients showed positive NIT results. CMD was defined as coronary flow reserve ≤2.5. According to the presence of INOCA and CMD, patients were classified into 4 groups: group 1 (no INOCA nor CMD, n=116); group 2 (only CMD, n=90); group 3 (only INOCA, n=41); and group 4 (both INOCA and CMD, n=40). The primary outcome was major adverse cardiovascular events, a composite of all‐cause death, target vessel myocardial infarction, or clinically driven target vessel revascularization at 5 years. Among 287 patients with nonobstructive coronary stenoses (fractional flow reserve=0.91±0.06), 81 patients (38.2%) were diagnosed with INOCA based on positive NIT. By intracoronary physiologic assessment, 130 patients (45.3%) had CMD. Regardless of the presence of INOCA, patients with CMD showed a significantly lower coronary flow reserve and higher hyperemic microvascular resistance compared with patients without CMD ( P <0.001 for all). The cumulative incidence of major adverse cardiovascular events at 5 years were 7.4%, 21.3%, 7.7%, and 34.4% in groups 1 to 4. By documenting CMD (groups 2 and 4), intracoronary physiologic assessment identified patients at a significantly higher risk of major adverse cardiovascular events at 5 years compared with group 1 (group 2: adjusted hazard ratio [HR _adjusted ], 2.88; 95% CI, 1.52–7.19; P =0.024; group 4: HR _adjusted , 4.00; 95% CI, 1.41–11.35; P =0.009). Conclusions: In stable patients with nonobstructive coronary stenoses, a diagnosis of INOCA based only on abnormal NIT did not identify patients with higher risk of long‐term cardiovascular events. Incorporating intracoronary physiologic assessment to NIT information in patients with nonobstructive disease allowed identification of patient subgroups with up to 4‐fold difference in long‐term cardiovascular events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04485234.

Background: As an initial treatment strategy, percutaneous coronary intervention (PCI) for coronary chronic total occlusion (CTO) did not show midterm survival benefits compared with optimal medical therapy (OMT). We sought to evaluate the benefit of PCI compared with OMT in patients with CTO over extended long‐term follow‐up. Methods and Results: Between March 2003 and February 2012, 2024 patients with CTO were enrolled in a single‐center registry and followed for ≈10 years. We excluded patients with CTO who underwent coronary artery bypass graft (n=477) and classified patients into the CTO‐PCI group (n=883) or OMT group (n=664) according to initial treatment strategy. Patients with multivessel disease received PCI for obstructive non‐CTO lesions in both groups. In the CTO‐PCI group, 699 patients (79.2%) underwent successful revascularization. The CTO‐PCI group had a lower 10‐year rate of cardiac death (10.4% versus 22.3%; hazard ratio [HR], 0.44 [95% CI, 0.32–0.59]; P <0.001) than the OMT group. After propensity score matching analyses, the CTO‐PCI group had a lower 10‐year rate of cardiac death (13.6% versus 20.8%; HR, 0.64 [95% CI, 0.45–0.91]; P =0.01) than the OMT group. The relative reduction in cardiac death at 10 years was mainly driven by a relative reduction between 3 and 10 years (8.3% versus 16.6%; HR, 0.43 [95% CI, 0.27–0.71]; P <0.001) but not at 3 years (5.7% versus 5.0%; HR, 1.12 [95% CI, 0.63–2.00]; P =0.71). The beneficial effects of CTO‐PCI were consistent among subgroups. Conclusions: As an initial treatment strategy, CTO‐PCI might reduce late cardiac death compared with OMT in patients with CTO. Extended follow‐up of randomized trials may confirm the findings of the present study.

Atherothrombotic events are influenced by systemic hypercoagulability and fibrinolytic activity. The present study evaluated thrombogenicity indices and their prognostic implications according to disease acuity. From the consecutive patients undergoing percutaneous coronary intervention (PCI), those with thrombogenicity indices (n = 2705) were grouped according to disease acuity [acute myocardial infarction (AMI) vs. non-AMI]. Thrombogenicity indices were measured by thromboelastography (TEG). Blood samples for TEG were obtained immediately after insertion of the PCI sheath, and TEG tracing was performed within 4 h post-sampling. Major adverse cardiovascular events (MACE, a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke) were evaluated for up to 4 years. Compared with non-AMI patients, AMI patients had higher platelet-fibrin clot strength [maximal amplitude (MA): 66.5 ± 7.8 vs. 65.3 ± 7.2 mm, P < 0.001] and lower fibrinolytic activity [clot lysis at 30 min (LY₃₀): 0.9 ± 1.8% vs. 1.1 ± 1.9%, P < 0.001]. Index AMI presentation was associated with MA [per one-mm increase: odds ratio (OR): 1.024; 95% confidence interval (CI): 1.013–1.036; P < 0.001] and LY₃₀ (per one% increase: OR: 0.934; 95% CI: 0.893–0.978; P = 0.004). The presence of high platelet-fibrin clot strength (MA ≥68 mm) and low fibrinolytic activity (LY₃₀ < 0.2%) was synergistically associated with MACE occurrence. In the multivariable analysis, the combined phenotype of ‘MA ≥ 68 mm’ and ‘LY₃₀ < 0.2%’ was a major predictor of post-PCI MACE in the AMI group [adjusted hazard ratio (HR): 1.744; 95% CI: 1.135–2.679; P = 0.011], but not in the non-AMI group (adjusted HR: 1.031; 95% CI: 0.499–2.129; P = 0.935). AMI occurrence is significantly associated with hypercoagulability and impaired fibrinolysis. Their combined phenotype increases the risk of post-PCI atherothrombotic event only in AMI patients. These observations may support individualized therapy that targets thrombogenicity for better outcomes in patients with AMI. Gyeongsang National University Hospital (G-NUH) Registry, NCT04650529. The association between thrombogenicity and AMI occurrence, and their prognostic implications for long-term cardiovascular outcomes were investigated. Abbreviations: AMI, acute myocardial infarction; HR, hazard ratio; LY30, percentage of the clot that has lysed 30 minutes after the time of maximum amplitude; MA, maximum amplitude; MACE, major adverse cardiovascular events; OR, odds ratio; PCI, percutaneous coronary intervention; TEG, thromboelastography.