Primary Reperfusion Research Articles

Focusing on women: dissecting sex-specific factors in cardiogenic shock through a large cohort and propensity score matching

Abstract Background Sex differences in cardiogenic shock (CS) are crucial for tailored interventions. We explored sex-based disparities a CS-registry encompassing both acute myocardial infarction (AMI) and non-AMI-CS. Purpose Investigate specific risk variables by type and sex of CS. Compare women-specific risk in CS types and through a propensity score matching (PSM). Methods 9430 patients in a CS registry, 4414 non-AMI-CS (2432 men, 1982 women) and 5016 AMI-CS (4025 men, 991 women). Utilized KM curves, Cox regression, and a multivariable model (for significant variables P<0.05) to identify sex-specific risk factors. Conducted PSM (K=1, 1:1 radius, caliper 0.2) for significant demographic and management variables, and incorporate age, DM2, MCS, PAC, mechanical ventilation (MV), hemodialysis, and exact for SCAI; and for AMI-CS, considered type of MI and primary reperfusion; to assess sex influence on CS mortality. Results Men with AMI an non-AMI-CS are younger, higher BMIs, and smoking history is more prevalent(P<0.05). Women with AMI had higher comorbidities, including HTN, HF, CKD, and AF(P<0.001). Conversely, men with non-AMI exhibit higher dyslipidemia, COPD, previous MI, PCI, and CABG(P<0.001). In terms of CS management, women with AMI are less likely to receive primary reperfusion(P<0.001), while women receive a higher number of vasoactive(P<0.001). Women receive less dobutamine and levosimendan in non-AMI-CS(P<0.001) but more norepinephrine in AMI & non-AMI(P<0.05), finally, more vasopressin in AMI-CS(P=0.006). The SCAI classification indicates that women with AMI tend to have a higher proportion of higher SCAI classes compared to men in AMI-CS (P<0.001) but comparable in non-AMI(P=0.296). Despite these differences, women experience higher mortality in both AMI & non-AMI(P<0.001 & 0.025).(Table 1) Also, different intensities in management strategies are seen by SCAI, and sex in general has been more intense in MCS(AMI) and vasoactive drugs(non-AMI) in men(data not shown). In multivariate analysis, we notice differences in the specific risk factors in men vs women.(Fig1). In mortality, had differences in both AMI and non-AMI-CS. In the case of AMI-CS Logrank(LR) P<0.001, 30 day-RMST of 2.11(1.12-3.08, P<0.001) days less, with a HR of 1.48(1.28-1.72, P<0.001) for women in AMI-CS. In non-AMI-CS LR P=0.006 in 30-days RSMT, a difference of diminished survival of 0.85(0.08-1.62, P=0.03) days, a HR of 1.18(1.05-1.32; P=0.007) for women in non-AMI-CS. (Fig1). When applying PSM, AMI-CS(931 vs 931) although differences arise in LR P=0.048, no differences are seen in 30-day RSMT 1.09(-0.17-2.35, P=0.09), HR 1.22(1.0-1.48, P=0.052). Non-AMI-CS(1406 vs 1406) no differences were appreciated(LR P=0.359), 30-day RSMT 0.4(-0.55-1.36, P=0.407), a HR 1.07(0.92-1.24, P=0.366). (Fig1). Conclusion Women's distinct risk factors may outweigh the impact of sex alone on outcomes. Sex-specific risk factors vary by CS type, underscoring the importance of tailored approaches.Table 1.Differences by CS type & sexFig 1.Forrest plot by CS type & sex

Mechanical right ventricular involvement is independent of right coronary arterial bed and has a prognostic impact in acute myocardial infarction complicated by cardiogenic shock

Abstract Background In Acute Myocardial Infarction complicated by Cardiogenic Shock(AMI-CS), understanding the implications of right ventricular involvement (RVi) is crucial for refining risk stratification and optimizing management. Purpose Distinguish the prognosis in RVi at baseline(RVB) and persistent(RVP) in AMI-CS Methods 357 patients with AMI-CS+PAC serial measures at 0, 6, 12, 24h. RVi was defined as the presence of all 4 criteria PAPI<1; RVSWi≤4.08; RAP≥15 mmHg; and PVC/PCP≥0.86 and persistent as the presence of the 4 criteria at 4 time points. For hemodynamic measures, repeated measures ANOVA; and KM curves and Cox regression were performed. Results 300 without vs 57 with RVB. Additionally, 344 without vs 13 had RVP. Killip-Kimball classification showed a higher significant association with both RVB(P=0.042). A higher percentage of RVB received vasopressin(P=0.008), and there was a significant association with levosimendan use(P=0.009) in RVP. The higher MODS score, RVB(P=0.017) and RVP(P=0.029). The number of vasoactives was higher in RVB(P=0.031) RVP(P=0.009). Finally, the phenotypic characterization revealed a significant association with RVB(P=0.001) and RVP(P=0.032) more cardio-metabolic. The SCAI-CSWG classification indicated a higher proportion in the E category for both RVB(P=0.046) and not significant in RVP(P=0.405). Overall, mortality rates did not differ significantly between in RVB(P=0.174) or RVP(P=0.117), although there was a trend towards higher mortality in patients with RVi. Age, sex, DM, HTN, previous MI, PCI, CABG, stroke, and type of MI, primary reperfusion, LVEF, and laboratory parameters did not differ. RVB had higher heart rate(P=0.036), RAP, PASP(both P<0.001), lower SBP(P=0.049), cardiac output(P=0.004), index(P=0.001), power(P=0.012), power index(P=0.002), CPI(RAP), perfusion pressure, PAPi(both P<0.001), Stroke volume(SV, P=0.001), SVi(P<0.001), LVSWi(P=0.001), and RVSWi(P<0.001). RVP higher RAP(<0.001), and lower cardiac output(P=0.008), index(P=0.005), power(P=0.034), power index(P=0.029), CPI(RAP)(P=0.002), perfusion pressure(P=0.035), PAPi(P<0.001), SV(P=0.018), SVi(P=0.011), LVSWi(P=0.034) RVSWi(P<0.001). Importantly interaction between group*time was found in RVB in RAP(P<0.001), mPAP(P=0.038), perfusion pressure(P=0.002) and RVSWi(P<0.001) and in RVP in SV(P=0.014), SVi(P=0.013) and LVSWi(P=0.028) suggest that RVi had different hemodynamic response. For RVB a reduction of -4.16 days in survival time (-7.79, -0.54, P=0.024); Logrank P=0.035. Similarly, for RVP demonstrated a significant reduction of -7.27 days (-14.08, -0.47, P=0.036); Logrank P=0.017. No significant of the culprit artery in RVB, RVP (P>0.05) was observed. RVB and RVP was strongly associated with a higher prevalence of RVi (STe-V3/4R) on ECG (35.1 vs. 11.7%, and 61.5 vs. 13.7%, P<0.001). Conclusion In AMI-CS, RVi, whether baseline or persistent, is associated with distinct hemodynamic profiles and a trend toward higher mortality.Figure 1.Hemodynamics of RVB(A-C) & RVP(D-F)Figure 2.Survival of RVB, RVP (A, B) & HR(C)

Prognostic importance of persistent elevations in high-sensitivity troponin T in the early convalescent phase (two weeks) following high-risk myocardial infarction: insights from the PARADISE-MI trial

Abstract Introduction Myocardial infarction (MI) is defined by a rise and fall in cardiac troponin (cTn) with clinical evidence of acute myocardial ischemia. How often cTn remains elevated in high-risk patients stabilized following MI and the relation between convalescent cTn levels and subsequent clinical outcomes in these patients is unknown. Aims To evaluate the prognostic importance of high-sensitivity cTn T (hs-cTnT) in the early convalescent phase of a MI for a range of cardiovascular (CV) outcomes in patients enrolled in the Prospective ARNI vs ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI). Methods Patients ≥18 years without prior heart failure (HF) (n=5661) were randomized to sacubitril/valsartan or ramipril within 0.5 to 7 days of MI complicated by transient pulmonary congestion, LVEF ≤40%, or both. Hs-cTnT was measured using the Roche Elecsys Troponin T-high-sensitive assay in 1093 patients two weeks after randomization (median 2.6 weeks after the index MI). Associations between log (2)-transformed hs-cTnT and clinical outcomes were investigated in landmark analyses using Cox regression models adjusted for clinical covariates of known prognostic importance and NT-proBNP (Figure). Results Median week 2 hs-cTnT concentration was 34 ng/L [IQR 17-94 ng/L] and exceeded the 99th percentile upper reference limit in 69% of patients. Patients with persistently elevated hs-cTnT concentrations (n=753) were older, more likely men, more commonly had atrial fibrillation and lower estimated glomerular filtration rate and less likely had a prior MI. They more commonly had presented with ST-segment elevation MI and pulmonary congestion and had higher concentrations of NT-proBNP. Rates of primary reperfusion were similar. Log(2)-transformed hs-cTnT was only weakly correlated with LVEF (rho = -0.15, p<0.001), irrespective of the type of MI. hs-cTnT was independently and linearly associated with the primary composite outcome of CV death or incident HF (adj HR 1.17 per doubling; 95% CI, 1.03 – 1.34), all-cause death (adj HR 1.20; 95% CI, 1.01 – 1.44) and CV death (adj HR 1.25; 95% CI, 1.02 – 1.52) but not with non-CV death (adj HR 1.04; 95% CI, 0.70-1.54). hs-cTnT was not significantly associated with recurrent fatal or non-fatal MI (adj HR 1.00; 95% CI, 0.85-1.18) (Figure). Concentrations of week 2 hs-cTnT were not altered by sacubitril/valsartan relative to ramipril (+4%; 95% CI, -8% to 18%). Conclusions Persistent elevations in hs-cTnT during the early convalescent phase following high-risk MI are common and are associated with heightened risk of all-cause death, CV death and incident HF but not of recurrent MI or non-CV death. hs-cTnT measured ~2.5 weeks after high-risk MI provides incremental prognostic information beyond traditional risk factors and NT-proBNP.

Differences in risk profiles and clinical outcomes according to age in patients with high-risk myocardial infarction: insights from the PARADISE-MI trial

Abstract Introduction Temporal declines in rates of rehospitalization and death after acute myocardial infarction (MI) have not been uniform across age groups. A better understanding of how risk profiles and clinical outcomes differ after MI by age may allow for targeted treatment and prevention strategies. Aims To investigate risk profiles and clinical outcomes following high-risk MI according to age in the Prospective ARNI vs ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI). Methods Adults without prior heart failure (HF) were randomized to sacubitril/valsartan versus ramipril within 0.5 to 7 days of a MI complicated by transient pulmonary congestion and/or left ventricular systolic dysfunction and additional risk-augmenting factors. Associations between age and clinical outcomes were analyzed using Cox proportional hazards regression models, which were additionally adjusted for baseline demographic and clinical covariates (Figure). Results The mean age of the 5,661 PARADISE-MI participants was 64 ± 11 years. Patients aged ≥75 years (n=1051) were more likely women, had more hypertension and atrial fibrillation and lower estimated glomerular filtration rate, were less likely to present with ST-segment elevation MI and regardless of type of MI were less likely to receive primary reperfusion and guideline-based medical therapy (Table). Age was significantly associated with all-cause death (HR 1.54 per 10-year increase; 95% CI, 1.41-1.68) and was more strongly associated with non-CV death (HR 2.09; 95% CI, 1.70-2.56) than with CV death (HR 1.43; 95% CI, 1.29-1.57). Age was also associated with incident HF (HR 1.37; 95% CI, 1.25-1.49) (Figure). Multivariable adjustment attenuated the risk relationship of age with recurrent fatal or non-fatal MI (HR 1.08; 95% CI, 0.96-1.21) and the coronary composite outcome (HR 1.01; 95% CI, 0.93-1.09). The relative treatment effect of sacubitril/valsartan versus ramipril on the primary composite outcome of CV death or incident HF was not significantly modified by age (p-interaction = 0.19). Conclusions Following high-risk MI, age was most strongly associated with subsequent non-CV death followed by CV death and incident HF, but was not independently associated with recurrent coronary events. The heightened risk of CV death and HF with advancing age was not explained by differences in clinical characteristics. Older patients may require closer surveillance and more aggressive treatment after MI to mitigate the elevated risk of CV death and HF.

Clinical Impact of Reperfusion Techniques and Occlusion Sites in Thrombectomy: Insights from the ASSIST Stroke Registry

BACKGROUND Mechanical thrombectomy has changed the landscape of acute ischemic stroke treatment, offering improved outcomes for patients with large vessel occlusions. The interplay between reperfusion techniques and occlusion sites remains a critical consideration in treatment decisions. This study investigates the impact of primary reperfusion techniques—stent retriever classic, stent retriever combination with aspiration, and direct aspiration—on procedural and clinical outcomes at different occlusion sites. METHODS Using data from the ASSIST registry, a prospective multinational initiative, patients with anterior circulation acute ischemic stroke with large vessel occlusions (n = 1477) were included. Three primary occlusion sites—M1 segment of the middle cerebral artery, M2 segment of the middle cerebral artery, and the internal carotid artery—were studied. Univariate tests and multivariable logistic regression models were used to assess associations between reperfusion techniques and procedural and clinical outcomes, including the expanded thrombolysis in cerebral infarction score and the modified Rankin Scale, stratified by occlusion site. RESULTS Achieving expanded thrombolysis in cerebral infarction ≥2c after first pass was lower in internal carotid artery occlusions (18.2%, P <0.0001) with direct aspiration alone compared with stent retriever classic (38.2%) or stent retriever combination with aspiration (43.3%), while no differences were seen for M1 segment of the middle cerebral artery ( P = 0.77) and M2 segment of the middle cerebral artery ( P = 0.29) occlusions. Bailout maneuvers, which were more frequent in the direct aspiration group for all occlusion sites, did not result in longer procedure times or different final recanalization outcomes in direct aspiration compared with stent retriever classic or stent retriever combination with aspiration. Overall, there were no differences in the rate of patients with modified Rankin Scale scores of 0–2 at 90 days. No differences in safety outcomes were observed. CONCLUSIONS This study provides insight into the complex relationship between reperfusion techniques and occlusion sites in patients with acute ischemic stroke and shows that certain techniques have advantages in certain occlusion sites. As the field evolves, further research is warranted to refine our understanding of these dynamics and inform clinical practice.

Attention to STEMI patients in our region: what is the adherence to the quality indicators from a population perspective?

Abstract Funding Acknowledgements None. Introduction The use of quality indicators (QI) proposed by the Association for Acute Cardiovascular Care (ACVC) for processes carried out in cardiology services represents an excellent internal quality control of their operation. Purpose The aim is to assess adherence to the main QI in the care of acute ST-elevation myocardial infarction (STEMI) in our region, according to data from the population-based registry of myocardial infarction in that area. Methods Evaluation of adherence to the main QI proposed by the ESC Association for ACVC, by retrospective analysis (data from in-hospital and out-of-hospital care) of patients with STEMI from our regional Infarction Registry attended between 2017 and 2020, in both tertiary and secondary hospitals of the public and private care network, providing data with a population-based character. Results QI were analysed in 1355 patients categorised as STEMI in our regional Infarction Registry between 2017 and 2020. 71% of patients were male. The number of STEMI per year ranged from 358 in 2019 to 316 in 2020. Primary percutaneous coronary intervention (PCI) was performed in 87% of patients. In 53% the first medical contact occurs in out-of-hospital care, while 25% occur in emergency departments (ED) of PCI capable hospitals and 12% in emergency departments of non-PCI hospitals. Forty-two percent of patients firstly attended out-of-hospital or in non-PCI centres achieve revascularisation in less than 90 minutes, but less than 30% of patients seen in PCI centres achieve revascularisation in less than 60 minutes. Radial access was used in 92% of cases. LVEF was assessed during admission in 98% and LDL-cholesterol was determined in 87%. Ninety-one per cent of patients were discharged on dual antiplatelet therapy, 96% on statins and a large proportion of patients with left ventricular dysfunction received angiotensin-converting enzyme inhibitors (78%) and beta-blockers (88%). Conclusion There is good overall adherence to major QI related to care of patients with STEMI in our region. However, there are indicators that could be optimised, particularly those related to timely primary reperfusion. Networked care thanks to the local Infarction Code means a significant reduction in reperfusion times, avoiding unnecessary referrals to Emergency Departments.

Reperfusion therapies in patients with intermediate- and high-risk pulmonary embolism: insights from a multicenter registry

Abstract Funding Acknowledgements None. Background Most acute pulmonary embolism (PE) patients receive anticoagulation as a sole treatment. Reperfusion therapies are required in high-risk (HR) and in intermediate-risk (IR)-PE patients with clinical deterioration. Systemic thrombolysis (ST) is the first-line reperfusion therapy, but due to contraindications and major bleeding concerns, catheter-directed therapies (CDT) are rising as a suitable alternative. Purpose The main objective of this study was to look for predictors that lead physicians to decide between different PE therapies in a contemporary cohort of patients. Methods This ambispective registry included consecutive IR- and HR-acute PE patients evaluated by local Pulmonary Embolism Response Team in two tertiary centers from 2014 to 2022. The patients were grouped according to the elected therapy: anticoagulation alone, CDT or ST. If more than one reperfusion therapy was used, the patient was assigned to the group of the first administered therapy. Predictors of reperfusion therapy assignment were evaluated using a logistic regression analysis. Also, early safety outcomes and procedural results after CDT were analyzed. Results A total of 274 patients were included. Of them, 112 received only anticoagulation, 96 received ST as primary treatment, and 66 underwent CDT at first. Baseline characteristics are displayed in Picture 1. Patients in the ST group were significantly younger (p<0.01). Comorbidities were higher in the CDT group compared to the other two. Patients undergoing CDT or ST had higher PE severity parameters at hospital admission than the anticoagulation group (e.g. shock index, RV involvement, or lactate levels; p<0.01 for all). The Pulmonary Embolism Severity Index score, which incorporates comorbidities and PE severity parameters, was higher in CDT patients compared to the other two groups (p<0.01). Picture 2 shows the trend in the choice between the two primary reperfusion therapies over the years. After multivariable analysis, the Charlson comorbidity index, recent surgery and bilateral central PE remained independent predictors for the use of CDT instead of ST (p<0.05 for all). A significant decrease in the systolic and mean pulmonary artery pressure and a significant increase in systolic blood pressure after procedure was detected in patients undergoing CDT. Regarding early safety outcomes, intracranial bleeding occurred only in the ST group. In contrast, the incidence of major bleeding, acute kidney injury and 30-day mortality did not differ between CDT and ST groups. Conclusion This contemporary registry used CDT as primary therapy in 24% of IHR and HR patients, mainly in comorbid and post-surgical patients, and increased over time. CDT was a safe and effective alternative to ST, achieving significant and early improvement in right ventricular function and hemodynamics.Baseline characteristicsChoice of reperfusion therapy over time

Standardized Pre-clinical Surgical Animal Model Protocol to Investigate the Cellular and Molecular Mechanisms of Ischemic Flap Healing

BackgroundSome of the most complex surgical interventions to treat trauma and cancer include the use of locoregional pedicled and free autologous tissue transfer flaps. While the techniques used for these reconstructive surgery procedures have improved over time, flap complications and even failure remain a significant clinical challenge. Animal models are useful in studying the pathophysiology of ischemic flaps, but when repeatability is a primary focus of a study, conventional in-vivo designs, where one randomized subset of animals serves as a treatment group while a second subset serves as a control, are at a disadvantage instigated by greater subject-to-subject variability. Our goal was to provide a step-by-step methodological protocol for creating an alternative standardized, more economical, and transferable pre-clinical animal research model of excisional full-thickness wound healing following a simulated autologous tissue transfer which includes the primary ischemia, reperfusion, and secondary ischemia events with the latter mimicking flap salvage procedure.ResultsUnlike in the most frequently used classical unilateral McFarlane’s caudally based dorsal random pattern skin flap model, in the herein described bilateral epigastric fasciocutaneous advancement flap (BEFAF) model, one flap heals under normal and a contralateral flap—under perturbed conditions or both flaps heal under conditions that vary by one within-subjects factor. We discuss the advantages and limitations of the proposed experimental approach and, as a part of model validation, provide the examples of its use in laboratory rat (Rattus norvegicus) axial pattern flap healing studies. ConclusionsThis technically challenging but feasible reconstructive surgery model eliminates inter-subject variability, while concomitantly minimizing the number of animals needed to achieve adequate statistical power. BEFAFs may be used to investigate the spatiotemporal cellular and molecular responses to complex tissue injury, interventions simulating clinically relevant flap complications (e.g., vascular thrombosis) as well as prophylactic, therapeutic or surgical treatment (e.g., flap delay) strategies in the presence or absence of confounding risk factors (e.g., substance abuse, irradiation, diabetes) or favorable wound-healing promoting activities (e.g., exercise). Detailed visual instructions in BEFAF protocol may serve as an aid for teaching medical or academic researchers basic vascular microsurgery techniques that focus on precision, tremor management and magnification.Graphical

Anti-inflammatory effects of quinolinyl analog of resveratrol targeting TLR4 in MCAO/R ischemic stroke rat model

BackgroundAmong adults, stroke is the main causes of mortality and permanent disability. Neuroinflammation is one of the main causes of stoke-mediated neuronal death. Our previous study revealed that (E)-5-(2-(Quinolin-4-yl) vinyl) benzene-1, 3-diol (RV01), a quinolinyl analog of resveratrol, inhibits microglia-induced neuroinflammation and safeguards neurons from inflammatory harm. The preventive role of RV01 in ischemic stroke and its underlying cellular mechanisms and molecular targets remain poorly understood. PurposeTo investigate whether RV01 alleviates ischemia-reperfusion (I/R) injury by inhibiting microglia-mediated neuroinflammation and determine the potential molecular mechanisms and targets by which RV01 inhibits the I/R-mediated microglia activation. MethodsRat middle cerebral artery occlusion and reperfusion (MCAO/R) and BV-2 or primary microglial cells oxygen-glucose deprivation and reperfusion (OGD/R) models were established. The neurological behavior scores, 2, 3, 5-triphenyl tetrazolium chloride staining and immunofluorescence were used to detect the neuroprotective effect of RV01 in the MCAO/R rats. In addition, the mRNA expression levels of IL-6, TNF-α, and IL-1β were detected to reveal the antineuroinflammatory effect of RV01. Moreover, a western blot assay was performed to explore the protein expression changes in NF-κB-mediated neuroinflammation. Finally, we identified TLR4 as an RV01 target through molecular docking, drug sensitivity target stability analysis, cellular thermal shift analysis, and surface plasmon resonance techniques. ResultsRV01 reduced the infarct volume and neurological deficits, increased the rotarod duration, and decreased the number of rightward deflections in the MCAO/R rats. RV01 inhibited the NF-κB signaling pathway in vitro and in vivo, as demonstrated by the reduction in the transcription factor p65-mediated expression of several inflammatory factors including IL-6, TNF-α, and IL-1β. Further studies showed that its protective effect was associated with targeting the TLR4 protein. Notably, the anti-inflammatory effect of RV01 was markedly reinforced by the TLR4 knockdown, but inhibited by the overexpression of TLR4. Results revealed that the conditioned medium derived from the RV01-treated BV-2 cells significantly decreased the OGD/R-mediated neuronal damage. ConclusionOur results are the first to reveal the protective effects of RV01 on cerebral ischemia, depending on its inhibitory effect on the NF-κB pathway by targeting TLR4. RV01 could be a potential protective agent in ischemic stroke treatment.

Facility-based approach for the management of acute ST segment elevation myocardial infarction with cardiogenic shock in a rural medical centre: the Durango model

IntroductionCardiogenic shock (CS) complicates 5%–15% of cases of acute myocardial infarction (AMI) with inpatient mortality greater than 40%. The implementation of standardised protocols may improve clinical outcomes in patients with...

Higher number vasopressor usage linked to poorer outcomes despite obtaining hemodynamic goals in acute myocardial infarction complicated by cardiogenic shock

Abstract Introduction Despite using vasoactive drugs to achieve hemodynamic goals in AMI-CS, the outcome of patients that achieve these goals and its relation with the number of drugs is uncertain. Methods 309 AMI-CS+PAC patients, divided by vasoactives 0-1, 2, or >2. Repeated measures ANOVA was used to compare 24-h hemodynamic data. The primary outcome was in-hospital mortality, and univariate and multivariate analyses were performed, adjusting for age, sex, type of MI, SCAI, multiorgan failure (MOF), and type of reperfusion. We also examined patients who achieved hemodynamic goals and analyzed the high achievers(≥5 goals) based on: MAP, CI, CPI, RAP, PCWP, and PAPI. Results 57 had 0-1, 76 =2, and 176 >2 vasoactives. Most patients were male(82%) with a median age 61(53-67) and had STEMI(82.8%). No differences in age, diabetes, previous HF, MI, PCI, CABG, smoking history, OHCA, or type of AMI. Killip-Kimball was overall worse in 2 and >2 groups(P<0.001). LVEF decreased as drugs increased (>2=30, 2=35, 0-1=40%; P<0.001). Higher leucocyte count, Cr, AST, ALT, LDH, and lactate with lower platelets, eGFR, and pH were seen as the number of drugs increased. No differences in Hb, electrolytes, albumin, C-reactive protein, primary reperfusion, angiography, number of vessels, or revascularization were noted. The use of mechanical ventilation and hemodialysis was lower in the 0-1 group. SCAI, MODS, MOF, and AKI were higher in 2 and >2 group. Mortality was higher in the>2 group(67.6) compared to 2 (31.6) and 0-1 (12.3%; P<0.001). In the serial measures, CI (Fig1A), CPO, CPI (Fig1B), CPIRAP, SBP, MAP, and PAPI(Fig1D,C) had lower values in the >2 group compared with the 2 or 0-1(P<0.001), whereas higher RAP and PCWP were seen in the >2 group(P<0.001, 0.009, Fig1E,F). The number of vasoactives was an independent predictor of mortality, and the estimated probability of mortality was higher as the number of drugs increased, despite achieving hemodynamic goals(Fig1; blue= 0-1, green=2, red >2). In the global cohort, patients receiving 2 or more vasoactive drugs had an increased hazard ratio compared to those receiving 0-1 drugs (Fig2C-D). Among high hemodynamic goal achievers (n=115), a difference in the Kaplan-Meier analysis was observed when compared with the 0-1 group, but no difference was seen with 2 drugs(HR 2.31[0.55-9.7; 0.252], HRadj 2.12[0.43-10.46; 0.358]). However, differences were observed when >2 drugs were used(HR 6.85[3.57-22.51; 0.002] and HRadj 7.38[1.96-27.77; 0.003])(Fig2B). In addition, a comparison of each variable subgroup achiever showed differences between the 0-1 and >2 vasoactives even after adjustment. In contrast, when compared vs 2 vasoactives, only CI, CPI, CPIRAP, and PAPI retained significance after adjustment(Fig2C-D). Conclusion Despite achieving hemodynamic goals in AMI-CS, the use of more vasoactive drugs may result in poorer outcomes. Furthermore, investigating strategies to reduce vasoactives, such as upfront MCS is warranted.Fig 1.Blue=0-1 Green=2 Red=>2 vasoactiveFig 2.

The Role of Nrf2 in Relieving Cerebral Ischemia-Reperfusion Injury.

Ischemic stroke includes two related pathological damage processes: brain injury caused by primary ischemia and secondary ischemia reperfusion (I/R) injury. I/R injury has become a worldwide health problem. Unfortunately, there is still a lack of satisfactory drugs for ameliorating cerebral I/R damage. Nrf2 is a vital endogenous antioxidant protein, which combines with Keap1 to maintain a dormant state under physiological conditions. When pathological changes such as I/R occurs, Nrf2 dissociates from Keap1 and activates the expression of downstream antioxidant proteins to exert a protective effect. Recent research have shown that the activated Nrf2 not only effectively inhibits oxidative stress, but also performs the ability to repair the function of compromised mitochondria, alleviate endoplasmic reticulum stress, eliminate inflammatory response, reduce blood-brain barrier permeability, inhibit neuronal apoptosis, enhance the neural network remolding, thereby exerting significant protective effects in alleviating the injuries caused by cell oxygen-glucose deprivation, or animal cerebral I/R. However, no definite clinical application report demonstrated the efficacy of Nrf2 activators in the treatment of cerebral I/R. Therefore, further efforts are needed to elaborate the role of Nrf2 activators in the treatment of cerebral I/R. Here, we reviewed the possible mechanisms underlying its potential pharmacological benefits in alleviating cerebral I/R injury, so as to provide a theoretical basis for studying its mechanism and developing Nrf2 activators.

COVID-19 infected ST-Elevation myocardial infarction in India (COSTA INDIA)

ObjectiveTo find out differences in the presentation, management and outcomes of COVID-19 infected STEMI patients compared to age and sex-matched non-infected STEMI patients treated during the same period. MethodsThis was a retrospective multicentre observational registry in which we collected data of COVID-19 positive STEMI patients from selected tertiary care hospitals across India. For every COVID-19 positive STEMI patient, two age and sex-matched COVID-19 negative STEMI patients were enrolled as control. The primary endpoint was a composite of in-hospital mortality, re-infarction, heart failure, and stroke. Results410 COVID-19 positive STEMI cases were compared with 799 COVID-19 negative STEMI cases. The composite of death/reinfarction/stroke/heart failure was significantly higher among the COVID-19 positive STEMI patients compared with COVID-19 negative STEMI cases (27.1% vs 20.7% p value = 0.01); though mortality rate did not differ significantly (8.0% vs 5.8% p value = 0.13). Significantly lower proportion of COVID-19 positive STEMI patients received reperfusion treatment and primary PCI (60.7% vs 71.1% p value=< 0.001 and 15.4% vs 23.4% p value = 0.001 respectively). Rate of systematic early PCI (pharmaco-invasive treatment) was significantly lower in the COVID-19 positive group compared with COVID-19 negative group. There was no difference in the prevalence of high thrombus burden (14.5% and 12.0% p value = 0.55 among COVID-19 positive and negative patients respectively) ConclusionsIn this large registry of STEMI patients, we did not find significant excess in in-hospital mortality among COVID-19 co-infected patients compared with non-infected patients despite lower rate of primary PCI and reperfusion treatment, though composite of in-hospital mortality, re-infarction, stroke and heart failure was higher.

Outcomes of Acute Coronary Syndrome Patients Who Presented with Cardiogenic Shock versus Patients Who Developed Cardiogenic Shock during Hospitalization.

Background: Cardiogenic shock (CS) continues to be a severe and fatal complication of acute coronary syndrome (ACS). CS patients have a high mortality rate despite significant progress in primary reperfusion, the management of heart failure and the expansion of mechanical circulatory support strategies. The present study addressed the clinical characteristics, management, and outcomes of ACS patients complicated with CS. Methods: We performed an observational study, using the 2000-2013 Acute Coronary Syndrome Israeli Surveys (ACSIS) database and identified hospitalizations of ACS patients complicated with CS. Patients' demographics and clinical characteristics, complications and outcomes were evaluated. We assessed the outcomes of ACS patients with CS at arrival (on the day of admission) compared with ACS patients who arrived without CS and developed CS during hospitalization. Results: The cohort included 13,434 patients with ACS diagnoses during the study period. Of these, 4.2% were complicated with CS; 224 patients were admitted with both ACS and CS; while 341 ACS patients developed CS only during the hospitalization period. The latter patients had significantly higher rates of MACEs compared with the group of ACS patients who presented with CS at arrival (73% vs. 51%; p < 0.0001). Similarly, the rates of in-hospital mortality (55% vs. 36%; p < 0.0001), 30-day mortality (64% vs. 50%; p = 0.0013) and 1-year mortality (73% vs. 59%; p = 0.0016) were higher in ACS patients who developed CS during hospitalization vs. ACS patients with CS at admission. There was a significant decrease in 1-year mortality trends during the 13 years of this study presented in ACS patients from both groups. Conclusions: Patients who developed CS during hospitalization had higher mortality and MACE rates compared with those who presented with CS at arrival. Further studies should focus on this subgroup of high-risk patients.

Clinical controversies in the management of acute pulmonary embolism: evaluation of four important but controversial aspects of acute pulmonary embolism management that are still subject of debate and research

ABSTRACT Introduction Acute pulmonary embolism (PE) is a disease with a broad spectrum of clinical presentations. While some patients can be treated at home or may even be left untreated, other patients require an aggressive approach with reperfusion treatment. Areas covered (1) Advanced reperfusion treatment in hemodynamically stable acute PE patients considered to be at high risk of decompensation and death, (2) the treatment of subsegmental pulmonary embolism, (3) outpatient treatment for hemodynamically stable PE patients with signs of right ventricle (RV) dysfunction, and (4) the optimal approach to identify and treatpost-PE syndrome. Expert opinion Outside clinical trials, hemodynamically stable acute PE patients should not be treated with primary reperfusion therapy. Thrombolysis and/or catheter-directed therapy are only to be considered as rescue treatment. Subsegmental PE can be left untreated in selected low-risk patients, after proximal deep vein thrombosis has been ruled out. Patients with an sPESI or Hestia score of 0 criteria can be treated at home, independent of the presence of RV overload. Finally, health-care providers should be aware of post-PE syndrome and diagnose chronic thromboembolic pulmonary disease (CTEPD) as early as possible. Persistently symptomatic patients without CTEPD benefit from exercise training and cardiopulmonary rehabilitation.

Effect of Rivaroxaban vs Enoxaparin on Major Cardiac Adverse Events and Bleeding Risk in the Acute Phase of Acute Coronary Syndrome

Parenteral enoxaparin is a preferred anticoagulant used in the acute phase for patients with acute coronary syndrome (ACS). The safety and efficacy of short-term low-dose rivaroxaban in this clinical setting remain unknown. To compare the safety and efficacy of rivaroxaban vs enoxaparin in the acute phase of ACS. This multicenter, prospective, open-label, active-controlled, equivalence and noninferiority trial was conducted from January 2017 through May 2021 with a 6-month follow-up at 21 hospitals in China. Participants included patients with ACS missing the primary reperfusion window or before selective revascularization. Data were analyzed from November 2021 to November 2022. Participants were randomized 1:1:1 to oral rivaroxaban 2.5 mg or 5 mg or 1 mg/kg subcutaneous enoxaparin twice daily in addition to dual antiplatelet therapy (DAPT; aspirin 100 mg and clopidogrel 75 mg once daily) for a mean of 3.7 days. The primary safety end point was bleeding events, as defined by the International Society on Thrombosis and Haemostasis, and the primary efficacy end point was major adverse cardiovascular events (MACEs), including cardiac death, myocardial infarction, rerevascularization, or stroke during the 6-month follow-up. Of 2055 enrolled patients, 2046 (99.6%) completed the trial (mean [SD] age 65.8 [8.2] years, 1443 [70.5%] male) and were randomized to enoxaparin (680 patients), rivaroxaban 2.5 mg (683 patients), or rivaroxaban 5 mg (683 patients). Bleeding rates were 46 patients (6.8%) in the enoxaparin group, 32 patients (4.7%) in the rivaroxaban 2.5 mg group, and 36 patients (5.3%)in the rivaroxaban 5 mg group (rivaroxaban 2.5 mg vs enoxaparin: noninferiority hazard ratio [HR], 0.68; 95% CI, 0.43 to 1.07; P = .005; rivaroxaban 5 mg vs enoxaparin: noninferiority HR, 0.88; 95% CI, 0.70 to 1.09; P = .001). The incidence of MACEs was similar among groups, and noninferiority was reached in the rivaroxaban 5 mg group (HR, 0.60; 95% CI, 0.31 to 1.16, P = .02) but not in the rivaroxaban 2.5 mg group (HR, 0.68; 95% CI, 0.36 to 1.30; P = .05) compared with the enoxaparin group. In this equivalence and noninferiority trial, oral rivaroxaban 5 mg showed noninferiority to subcutaneous enoxaparin (1 mg/kg) for patients with ACS treated with DAPT during the acute phase. Results of this feasibility study provide useful information for designing future randomized clinical trials with sufficient sample sizes. ClinicalTrials.gov Identifier: NCT03363035.

Systemic thrombolytic and ultrasound-assisted catheter-directed thrombolysis for treatment of acute pulmonary embolism: a 7-year, multicenter experience.

Treatment of acute pulmonary embolism (PE) varies based upon risk stratification and ranges from outpatient oral anticoagulation to emergency surgical embolectomy. Patients with high-risk PE can be considered for systemic thrombolytic (ST) based upon guideline recommendations, but intermediate-risk PE does not currently have strong evidence to guide primary reperfusion strategies via thrombolytic administration. Ultrasound-assisted catheter-directed thrombolysis (USAT) is an alternative reperfusion option to ST but is not currently recommended as first line in any key guidelines due to limited available evidence. This retrospective, multicenter, observational study compares 210 patients treated with USAT (n = 105) or ST (n = 105) for acute high- or intermediate-risk PE in three hospitals. Baseline characteristics were significant in that severity of illness was higher in those that received ST, which limited comparisons of outcomes. The primary outcome of major bleeding in patients receiving USAT was 15.2% and 22.9% in those that received ST. Efficacy of reperfusion strategy was observed to be 86.7% of patients in USAT group and 65.7% in ST group. Reperfusion strategies had no difference in in-hospital death, intensive care length of stay, or hospital length of stay. Predefined subgroup analysis found that high-risk PE had higher mortality (14.7%) than intermediate-risk PE (0%) regardless of reperfusion strategy. Upon multivariate analysis, high-risk PE was the only independent risk factor for major bleeding while USAT therapy and intermediate-risk PE were independent predictors of efficacy. Due to the difference in baseline severity of illness, direct comparisons in primary outcomes to each group was not performed. We have described real world usage of both USAT and ST and which patients were likely to receive each therapy at these institutions.

681 RIGHT ARM PAIN WITH RIGHT BUNDLE BRANCH BLOCK: SHOULD WE PERFORM TROPONIN ASSAY?

Abstract We present the case report of a 67 year old man with no previous cardiovascular history, who was admitted to our emergency department (ED) for two days onset of right arm pain which was not responsive to painkillers. On admission, he was asymptomatic for typical angina. His BP was 190/100 mmHg, HR 80 bpm, SpO2 99% and apyretic. The clinical examination was unremarkable. The ECG showed sinus rhythm, complete right-bundle-branch-block (RBBB) and left-axis deviation, negative T-waves in V1-V2 and positive T-waves in V3 &amp;gt; V6 (figure 1A) (no previous ECGs were available). The blood samples showed normal renal function and blood count. Surprisingly, there was a progressive rise in troponin I levels 0.023 &amp;gt; 0.061 &amp;gt; 0.38 ng/ml (ULN 0.010 ng/ml). Echocardiography revealed preserved LVEF without major regional wall motion abnormalities (RWMA), nor any valvulopathy. Despite the atypical presentation and ECG, the troponin rise was strongly suggestive for an acute coronary syndrome (ACS), so the patient was sent to the Cath lab to undergo coronary angiography (CAG). At the time of the CAG he was asymptomatic. The exam revealed thrombotic occlusion of mid-segment left anterior descending artery (LAD). Primary PCI with DES implantation was performed obtaining TIMI 3 flow (figure2). The remaining hospital stay was uneventful, the patient was discharged asymptomatic after 4 days. Pre-discharge echocardiography reported normal LVEF with no RWMA. Discharge ECG showed persistency of the RBBB with negative T-waves from V1 to V4 (figure 1B). On 3 months follow up visit the patient is asymptomatic with preserved LVEF. On ECG there is persistency of RBBB and normalization of the T-waves in the precordial leads (figure 1C). Discussion This case report is an atypical presentation of acute thrombotic occlusion of an epicardial coronary artery, without the typical ST segment elevation (STEMI equivalent) and without the typical angina. RBBB may represent an uncommon ECG presentation of acute myocardial ischemia, with an incidence from 2 to 6% overall, with TIMI 0 flow in the infarct-related artery only in half of the cases. RBBB (especially new or presumably new onset RBBB) is also associated with increased mortality and morbidity, possibly due to delay in diagnosis and primary reperfusion strategies. Troponin dosage was fundamental to understand that we were facing an acute coronary syndrome, however we were not expecting complete occlusion of the LAD. In conclusion, the presence of RBBB on admission may delay primary reperfusion strategies, especially when symptoms are atypical. However, in case of unresponsive pain and presumably new-onset conduction disturbances on ECG it is mandatory to perform troponin assay and therefore drive the correct timing of coronary revascularization.

A STUDY ON THE PROGNOSTIC SIGNIFICANCE OF HYPONATREMIA IN ACUTE MYOCARDIAL INFARCTION- A PROSPECTIVE LONGITUDINAL STUDY

Background: Hyponatremia, dened as a serum sodium concentration &lt;135 mEq/L, is the most common electrolyte disorder in hospitalized patients. Hyponatremia also increases the morbidity and mortality following myocardial infarction. MI is a major cause of death and is a global health problem reaching epidemic in both developed as well as in developing countries. Aims and Objectives: To study hyponatremia as a prognostic marker in patients with acute myocardial infarction-STEMI and NSTEMI. Material and Methods: This prospective, longitudinal observational study was conducted during December 2018 – October 2020 in 152 cases of acute MI. Results: Male preponderance in the patients hospitalised due to acute MI was 73.03%. The mean age of females was 59.46±9.42 years affected by acute MI was more than males i.e. 53.23±9.92 years. Hyponatremia was present in 39.47% of the cases with acute MI. Mild hyponatremia was the most prevalent 71.67% and severe hyponatremia was the least prevalent 3.33%. Diabetes mellitus was more prevalent in cases of MI with hyponatremia 53.33% vs 25%. The GRACE scores were higher in the cases having hyponatremia and increases with the increase in severity of hyponatremia. The TIMI scores were higher in the cases having hyponatremia and increases with the increase in severity of hyponatremia. The mean duration of hospital stay was 9.99 ± 8.69 days. STEMI was more prevalent 75.66% than NSTEMI. AWMI cases were more in the population with hyponatremia 78% than in the population with normal serum sodium 53.85%. Acute MI cases with hyponatremia had lower mean LVEF than those with normal serum sodium levels. Primary reperfusion therapy (thrombolysis/primary PCI) was done in 44.08% of the cases and no signicant association was found between it and outcomes in the hyponatremia group. Complications were present in 23.03% of the cases in hyponatremia group (p &lt;0.05). Mortality was present in 2.64% of the cases and more common in the cases with hyponatremia (p&gt;0.05). The odds of complications (including death) was 2.91 times in the cases with hyponatremia as compared to cases with normal serum sodium levels, 2.47 times in the cases with mild hyponatremia as compared to cases with normal serum sodium levels, 3.42 times in the cases with moderate hyponatremia as compared to cases with normal serum sodium levels and 25 times in the cases severe hyponatremia as compared to cases with normal serum sodium levels. Conclusion: It can be concluded that the severity of MI is more in cases with hyponatremia and hyponatremia is associated with poorer outcomes in terms of complications post MI and mortality.

Percutaneous treatment options for acute pulmonary embolism: a clinical consensus statement by the ESC Working Group on Pulmonary Circulation and Right Ventricular Function and the European Association of Percutaneous Cardiovascular Interventions.

There is a growing clinical and scientific interest in catheter-directed therapy (CDT) of acute pulmonary embolism (PE). Currently, CDT should be considered for patients with high-risk PE, in whom thrombolysis is contraindicated or has failed. Also, CDT is a treatment option for initially stable patients in whom anticoagulant treatment fails, i.e., those who experience haemodynamic deterioration despite adequately dosed anticoagulation. However, the definition of treatment failure (primary reperfusion therapy or anticoagulation alone) remains an important area of uncertainty. Moreover, several techniques for CDT are available without evidence supporting one over the other, and variation in practice with regard to periprocedural anticoagulation is considerable. The aim of this position paper is to describe the currently available CDT approaches in PE patients and to standardise patient selection, the timing and technique of the procedure itself as well as anticoagulation regimens during CDT. We discuss several clinical scenarios of the clinical evaluation of the "efficacy" of thrombolysis and anticoagulation, including treatment failure with haemodynamic deterioration and treatment failure based on a lack of improvement. This clinical consensus statement serves as a practical guide for CDT, complementary to the formal guidelines.