Efficacy of Coronary Sinus Pacing for Cardiogenic Shock Due to Percutaneous Coronary Intervention-induced Sick Sinus Syndrome: Two Case Reports.

We herein report two cases of atrial pacing with coronary sinus (CS) pacing performed to improve hemodynamic instability in cardiogenic shock due to percutaneous coronary intervention (PCI)-induced sick sinus syndrome (SSS). Ventricular pacing alone made it difficult to stabilize hemodynamics due to SSS, which had been caused by the lack of reflow and slow flow of the sinus node artery (SNA) jailed with a stent. Adding atrial pacing with CS pacing may be useful, as in our two cases, where ventricular pacing alone was unable to stabilize hemodynamics.

A novel extracorporeal cardiopulmonary resuscitation strategy using a hybrid emergency room for patients with pulseless electrical activity.

BACKGROUND: Whether extracorporeal cardiopulmonary resuscitation (ECPR) is indicated for patients with pulseless electrical activity (PEA) remains unclear. Pulmonary embolism with PEA is a good candidate for ECPR; however, PEA can sometimes include an aortic disease and intracranial haemorrhage, with extremely poor neurological outcomes, and can thus not be used as a suitable candidate. We began employing an ECPR strategy that utilised a hybrid emergency room (ER) to perform computed tomography (CT) before extracorporeal membrane oxygenation (ECMO) induction from January 2020. Therefore, the present study aimed to evaluate the effectiveness of this ECPR strategy. METHODS: Medical records of patients who transferred to our hybrid ER and required ECPR for PEA between January 2020 and November 2021 were reviewed. RESULTS: Twelve consecutive patients (median age, 67 [range, 57-73] years) with PEA requiring ECPR were identified in our hybrid ER. Among these patients, nine were diagnosed using an initial CT scan (intracranial haemorrhage (3); cardiac tamponade due to aortic dissection (3); aortic rupture (2); and cardiac rupture (1)), and unnecessary ECMO was avoided. The remaining three patients underwent ECPR, and two of them survived with favourable neurological outcomes. Patients not indicated for ECPR were excluded before ECMO induction. CONCLUSION: Our ECPR strategy that involved the utilisation of a hybrid ER may be useful for the exclusion of patients with PEA not indicated for ECPR and decision making.

Successful interhospital transfer for extracorporeal cardiopulmonary resuscitation of a patient who had a cardiac arrest after cesarean section.

BACKGROUND: Studies describing the effectiveness of extracorporeal cardiopulmonary resuscitation (ECPR) for peripartum cardiopulmonary arrest are lacking. CASE PRESENTATION: A 39-year-old woman underwent elective cesarean section. Right after surgery, she fell into a cardiac arrest and was promptly transferred to our institute by ambulance. On arrival, we immediately initiated ECPR, within 63 min of the cardiac arrest. Return of spontaneous circulation was achieved 80 min after induction of extracorporeal membrane oxygenation. As the hemodynamics of the patient stabilized, extracorporeal membrane oxygenation was discontinued on day 3 of hospitalization. The patient's cerebral performance category score was 3 at discharge, which improved to 2 after 3 months. CONCLUSION: This case suggests that prompt interhospital transfer and ECPR might be effective for peripartum cardiac arrest due to nonhemorrhagic events.

Association Between Converting Asystole From Initial Shockable ECG Rhythm Before Extracorporeal Cardiopulmonary Resuscitation and Outcome.

BACKGROUND: Initial electrocardiogram (ECG) rhythm is a predictor of outcomes in out-of-hospital cardiac arrest (OHCA) in patients receiving extracorporeal cardiopulmonary resuscitation (ECPR). However, ECG rhythm often changes before ECPR, and the consequence of this change remains unclear. This study aimed to assess the relationship between the conversion of ECG rhythm from initial shockable rhythm before ECPR and mortality. PATIENTS AND METHODS: This was a retrospective cohort study of OHCA patients with initial shockable rhythm who underwent ECPR between January 2010 and September 2020. Patients were classified into two groups: asystole (patients whose ECG rhythm converted to asystole at any time before initiating ECPR) and non-asystole (patients whose ECG rhythm did not convert to asystole at any time before initiating ECPR) groups. The primary outcome was in-hospital mortality. RESULTS: A total of 102 patients were included in the study; in-hospital mortality rate was 46.1% (n = 47) and 76 (74.5%) patients had unfavorable neurological outcomes (Cerebral Performance Category: 3-5). There were 33 and 69 patients in the asystole and non-asystole groups, respectively. The mortality rates in the asystole and non-asystole groups were 69.7% and 34.8%, respectively (P = 0.001). On multivariable analysis, the asystole group showed a significant association with mortality (odds ratio, 5.42; 95% confidence interval, 2.11-15.36; P < 0.001). CONCLUSION: Conversion to asystole before ECPR at any time in patients with OHCA is associated with mortality in patients with an initial shockable ECG rhythm.

Impact of the Antithrombotic Effects of Prasugrel on Mid-Term Vascular Healing in Acute Coronary Syndrome vs. Stable Coronary Artery Disease.

BACKGROUND: The impact of antiplatelet drug effects on mid-term local arterial responses following percutaneous coronary intervention (PCI) remains uncertain. We evaluated the impact of the platelet reactivity of prasugrel on mid-term vascular healing between acute coronary syndrome (ACS) and stable coronary artery disease (CAD).Methods and Results:We conducted a prospective, 12-center study in 125 patients with ACS and 126 patients with stable CAD who underwent PCI with an everolimus-eluting stent (EES) and received dual antiplatelet therapy (DAPT) with prasugrel and aspirin. Serial optical coherence tomography (OCT) was performed immediately after PCI and at the 9-month follow-up to assess the association of P2Y12reaction units (PRU) with the frequency of malapposed or uncovered struts and intrastent thrombi (IST). The incidence of abnormal mid-term OCT findings did not different between the ACS and CAD arms, regardless of clinical presentation, except that uncovered struts were more frequent in the ACS than CAD arm. PRU at PCI was significantly associated with the frequency of IST at follow-up, but not with uncovered and malapposed struts. PRU at PCI was the only independent predictor of IST detected at follow-up (odds ratio 1.009). CONCLUSIONS: In patients undergoing EES implantation and receiving prasugrel, achieving an adequate antiplatelet effect at the time of stent implantation may regulate thrombus formation throughout the follow-up period.

Early and Mid-Term Vascular Responses to Optical Coherence Tomography-Guided Everolimus-Eluting Stent Implantation in Stable Coronary Artery Disease.

BACKGROUND: Analysis of pooled clinical data has shown the safety of 3 months of dual antiplatelet therapy with everolimus-eluting cobalt-chromium stents (Co-Cr EESs). This study evaluated early and mid-term vascular responses to Co-Cr EESs in patients with stable coronary artery disease. METHODS: The Multicenter Comparison of Early and Late Vascular Responses to Everolimus-Eluting Cobalt-Chromium Stent and Platelet Aggregation Studies in Patients With Stable Angina Managed as Elective Case (MECHANISM-Elective) study (NCT02014818) is a multicenter optical coherence tomography (OCT) registry. Enrolled patients were evaluated by OCT immediately after everolimus-eluting stent implantation were prospectively allocated to 1 month (n = 50) or 3 months (n = 50) OCT follow-up and then received a 12-month OCT evaluation. The incidences of intrastent thrombus (IS-Th) and irregular protrusion (IRP) were also assessed. RESULTS: The percentage of uncovered struts was 6.4% ± 10.3% at 1 month (P < 0.001 vs. postprocedure) and 0.5% ± 0.9% at 12 months (P < 0.001 vs. 1 month). The corresponding values in the 3-month cohort were 2.0% ± 2.5% (P < 0.001 vs. postprocedure) and 0.5% ± 1.5% (P < 0.001 vs. 3 months). The incidence of IS-Th was 32.7% at 1 month, 5.4% at 3 months, and 2.0% at 12 months. IRP was observed in 21.8% of patients post-EES but had totally resolved at 1, 3, and 12 months. CONCLUSION: Early and mid-term vascular reactions after Co-Cr EES implantation in stable patients with coronary artery disease in the MECHANISM-Elective included dynamic resolution of IS-Th and IRP and rapid decrease in uncovered struts. Thus, EES may allow shortening of dual antiplatelet therapy duration less than 3 months in this patient subset.

Impact of dual antiplatelet therapy with adjusted-dose prasugrel on mid-term vascular response in patients undergoing elective percutaneous coronary intervention with everolimus-eluting stents.

The impact of dual antiplatelet therapy (DAPT) with adjusted-dose (3.75 mg/day) prasugrel for Japanese patients has not been fully investigated in terms of local arterial healing following the elective percutaneous coronary intervention (PCI). The ROUTE-01 elective study was a prospective, 12-center and single-arm registry that enrolled 123 patients who underwent elective PCI with everolimus-eluting stents (EESs) under DAPT with a combination of adjusted-dose prasugrel and aspirin. Serial optical coherence tomography (OCT) was performed at the index PCI and 9-month follow-up to assess the relationship between in-stent thorombus (IST) and residual platelet reactivity measuring platelet reactivity unit (PRU). The patients were classified as extensive, intermediate, and poor metabolizers by cytochrome P450 2C19 (CYP2C19) loss-of-function polymorphisms. The prevalence of IST was 9.0% by 9-month OCT, with no difference amongst the three groups (p = 0.886). The incidences of malapposed and uncovered struts were not different among the groups. PRU was not statistically different among the groups. In multivariate logistic regression analysis, the independent predictor for IST on 9-month OCT was irregular protrusion (odds ratio = 8.952, p = 0.037) on post-PCI OCT, not CYP2C19 loss-of-function polymorphisms. An adequate anti-thrombotic effect with an acceptable incidence of IST was observed irrespective of CYP2C19 loss-of-function polymorphisms. Our data suggests that adjusted-dose prasugrel and aspirin is a feasible treatment option in Japanese patients treated with EESs in elective PCI.

Impact of the angiographic burden on the incidence of out-of-hospital ventricular fibrillation in patients with acute myocardial infarction.

Ventricular fibrillation (VF) is a catastrophic complication of spontaneous (type 1) acute myocardial infarction (AMI). This study sought to clarify the angiographic coronary characteristics related to out-of-hospital VF in AMI patients. We retrospectively reviewed 464 consecutive cases of suspicious AMI, including type 1 AMI, with or without out-of-hospital VF. In addition to patient demographics, proximal left coronary artery (LCA) disease, multivessel disease (MVD), and chronic total occlusion (CTO) were assessed via coronary angiography and compared between patients with and without out-of-hospital VF. Coronary angiography was evaluated for 74 patients with out-of-hospital VF and for 237 without. Male sex (93.2 vs. 83.1%; P = 0.036), Killip class ≥ 2 (89.2 vs. 16.5%; P < 0.001), and ST elevation myocardial infarction (83.8 vs. 66.7%; P = 0.003) were more frequent in the out-of-hospital VF group. The culprit lesions located in the proximal left coronary artery (62.2 vs. 29.5%; P < 0.001), MVD (75.7 vs. 41.8%, P < 0.001), and CTO (43.2 vs. 10.5%, P < 0.001) were more frequently observed in patients with out-of-hospital VF. Multivariate logistic regression analysis identified the culprit lesion located in the proximal LCA [odds ratio (OR) 2.86; 95% confidence interval (CI) 1.34-6.08], the presence of CTO (OR 8.52; 95% CI 3.35-21.65), and MVD (OR 3.69; 95% CI 1.57-8.65) as predictors of out-of-hospital VF. For type 1 AMI patients, advanced disease burden including the culprit lesion located in the proximal LCA and coexistence of CTO or MVD might be associated with out-of-hospital VF.

Sphingosine kinase 2 is a nuclear protein and inhibits DNA synthesis.

Sphingosine kinase-1 (SPHK1) is a key enzyme catalyzing the formation of an important bioactive lipid messenger, sphingosine 1-phosphate, and is implicated in the regulation of cell proliferation and antiapoptotic processes. Biological features of another isozyme SPHK2, however, remain unclear. The present studies were undertaken to characterize SPHK2 by comparison with SPHK1. When SPHK2 was transiently expressed in various cell lines, it was localized in the nuclei as well as in the cytosol, whereas SPHK1 was distributed in the cytosol but not in the nucleus. We have mapped a functional nuclear localization signal (NLS) to the N-terminal region of SPHK2. We have observed that the expression of SPHK2 in various cell types causes inhibition of DNA synthesis, resulting in the cell cycle arrest at G1/S phase. We have also demonstrated that an NLS mutant of SPHK2, SPHK2R93E/R94E, failed to enter the nucleus and to inhibit DNA synthesis. Moreover, a fusion protein, NLS-SPHK1, where SPHK1 was fused to the NLS sequence of SPHK2 acquired the ability to enter nuclei and inhibited DNA synthesis. These results indicate that SPHK2 localizes in the nuclei and causes inhibition of DNA synthesis, and this may affect subsequent cellular events.

Identification and characterization of RPK118, a novel sphingosine kinase-1-binding protein.

Sphingosine kinase (SPHK) is a key enzyme catalyzing the formation of sphingosine 1 phosphate (SPP), a lipid messenger that is implicated in the regulation of a wide variety of important cellular events through intracellular as well as extracellular mechanisms. However, the molecular mechanism of the intracellular actions of SPP remains unclear. Here we have cloned a novel sphingosine kinase-1 (SPHK1)-binding protein, RPK118, by yeast two-hybrid screening. RPK118 contains several functional domains whose sequences are homologous to other known proteins including the phox homology domain and pseudokinase 1 and 2 domains and is shown to be a member of an evolutionarily highly conserved gene family. The pseudokinase 2 domain of RPK118 is responsible for SPHK1 binding as judged by yeast two-hybrid screening and immunoprecipitation studies. RPK118 is also shown to co-localize with SPHK1 on early endosomes in COS7 cells expressing both recombinant proteins. Furthermore, RPK118 specifically binds to phosphatidylinositol 3-phosphate. These results strongly suggest that RPK118 is a novel SPHK1-binding protein that may be involved in transmitting SPP-mediated signaling into the cell.