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1.
Open Heart ; 11(1)2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38843905

ABSTRACT

BACKGROUND: There is increasing awareness that patients without standard modifiable risk factors (SMuRFs; diabetes, hypercholesterolaemia, hypertension and smoking) may represent a unique subset of patients with acute coronary syndrome (ACS). We aimed to investigate the prevalence and outcomes of patients with SMuRF-less ACS undergoing percutaneous coronary intervention (PCI) compared with those with SMuRFs. METHODS: We analysed data from the Melbourne Interventional Group PCI Registry. Patients with coronary artery disease were excluded. The primary outcome was 30-day mortality. Secondary outcomes included in-hospital and 30-day events. Long-term mortality was investigated using Cox-proportional hazards regression. RESULTS: From 1 January 2005 to 31 December 2020, 2727/18 988 (14.4%) patients were SMuRF less, with the proportion increasing over time. Mean age was similar for patients with and without SMuRFs (63 years), and fewer females were SMuRF-less (19.8% vs 25.4%, p<0.001). SMuRF-less patients were more likely to present with cardiac arrest (6.6% vs 3.9%, p<0.001) and ST-elevation myocardial infarction (59.1% vs 50.8%, p<0.001) and were more likely to experience postprocedural cardiogenic shock (4.5% vs 3.6%, p=0.019) and arrhythmia (11.2% vs 9.9%, p=0.029). At 30 days, mortality, myocardial infarction, revascularisation and major adverse cardiac and cerebrovascular events did not differ between the groups. During median follow-up of 7 years, SMuRF-less patients had an adjusted 13% decreased rate of mortality (HR 0.87 (95% CI 0.78 to 0.97)). CONCLUSIONS: The proportion of SMuRF-less patients increased over time. Presentation was more often a devastating cardiac event compared with those with SMuRFs. No difference in 30-day outcomes was observed and SMuRF-less patients had lower hazard for long-term mortality.


Subject(s)
Acute Coronary Syndrome , Percutaneous Coronary Intervention , Registries , Humans , Acute Coronary Syndrome/therapy , Acute Coronary Syndrome/mortality , Acute Coronary Syndrome/epidemiology , Acute Coronary Syndrome/surgery , Female , Male , Percutaneous Coronary Intervention/adverse effects , Middle Aged , Prevalence , Aged , Risk Factors , Treatment Outcome , Time Factors , Risk Assessment/methods , Retrospective Studies , Follow-Up Studies , Survival Rate/trends , Hospital Mortality/trends , Victoria/epidemiology
2.
Article in English | MEDLINE | ID: mdl-38876940

ABSTRACT

BACKGROUND: The American College of Cardiology / American Heart Association (ACC/AHA) introduced a coronary lesion classification in 1988 to stratify coronary lesions for probability of procedural success and complications after coronary angioplasty. Our aim is to assess the validity of the ACC/AHA lesion classification in predicting outcomes of percutaneous coronary intervention (PCI) in a contemporary cohort of patients. METHODS: Consecutive PCI procedures performed between 2005 and 2018, were divided into three periods. At each period, the ACC/AHA lesion classification (A, B1, B2, C) was analysed with respect to procedural characteristics, in-hospital and 30-day outcomes, as well as long-term mortality by linkage to the National Death Index (NDI). RESULTS: In total, 21,437 lesions were included with 7399 lesions (2005-2009), 6917 lesions (2010-2014) and 7121 lesions (2015-2018). There was a progressive increase in the number of complex lesions treated over time with ACC/AHA type C (15 %, 21 % and 26 %, p < 0.01). The rate of PCI procedural success decreased with increase in the complexity of lesions treated across all three periods (p < 0.01). Further, in-hospital and 30-day major adverse cardiovascular events (MACE), major adverse cardiac and cerebrovascular events (MACCE) increased across all three time periods (all p < 0.05). CONCLUSIONS: Our study validates the ACC/AHA lesion classification as a meaningful tool for prediction of PCI outcomes. Despite advances in PCI techniques and technology, complex lesion PCI defined by this classification continues to be associated with adverse outcomes.

3.
Circ Cardiovasc Interv ; 17(4): e013738, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38487882

ABSTRACT

BACKGROUND: Suboptimal coronary reperfusion (no reflow) is common in acute coronary syndrome percutaneous coronary intervention (PCI) and is associated with poor outcomes. We aimed to develop and externally validate a clinical risk score for angiographic no reflow for use following angiography and before PCI. METHODS: We developed and externally validated a logistic regression model for prediction of no reflow among adult patients undergoing PCI for acute coronary syndrome using data from the Melbourne Interventional Group PCI registry (2005-2020; development cohort) and the British Cardiovascular Interventional Society PCI registry (2006-2020; external validation cohort). RESULTS: A total of 30 561 patients (mean age, 64.1 years; 24% women) were included in the Melbourne Interventional Group development cohort and 440 256 patients (mean age, 64.9 years; 27% women) in the British Cardiovascular Interventional Society external validation cohort. The primary outcome (no reflow) occurred in 4.1% (1249 patients) and 9.4% (41 222 patients) of the development and validation cohorts, respectively. From 33 candidate predictor variables, 6 final variables were selected by an adaptive least absolute shrinkage and selection operator regression model for inclusion (cardiogenic shock, ST-segment-elevation myocardial infarction with symptom onset >195 minutes pre-PCI, estimated stent length ≥20 mm, vessel diameter <2.5 mm, pre-PCI Thrombolysis in Myocardial Infarction flow <3, and lesion location). Model discrimination was very good (development C statistic, 0.808; validation C statistic, 0.741) with excellent calibration. Patients with a score of ≥8 points had a 22% and 27% risk of no reflow in the development and validation cohorts, respectively. CONCLUSIONS: The no-reflow prediction in acute coronary syndrome risk score is a simple count-based scoring system based on 6 parameters available before PCI to predict the risk of no reflow. This score could be useful in guiding preventative treatment and future trials.


Subject(s)
Acute Coronary Syndrome , Myocardial Infarction , No-Reflow Phenomenon , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Adult , Humans , Female , Middle Aged , Aged , Male , Percutaneous Coronary Intervention/adverse effects , Acute Coronary Syndrome/diagnostic imaging , Acute Coronary Syndrome/therapy , Coronary Angiography , Treatment Outcome , Risk Factors , Myocardial Infarction/etiology , ST Elevation Myocardial Infarction/diagnostic imaging , ST Elevation Myocardial Infarction/therapy , ST Elevation Myocardial Infarction/etiology , No-Reflow Phenomenon/diagnostic imaging , No-Reflow Phenomenon/etiology
4.
Am J Cardiol ; 219: 25-34, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38447892

ABSTRACT

Metabolic syndrome (MetS) provides significant risk for coronary disease, however long-term prognosis after percutaneous coronary intervention (PCI) has been understudied. We assessed the prevalence and outcomes of patients with MetS from an Australian PCI cohort. We retrospectively examined data from the Melbourne Interventional Group multicenter PCI registry using a modified definition for MetS including ≥3 of the following: hypertension, diabetes mellitus, dyslipidemia, and body mass index ≥30 kg/m2. Thirty-day outcomes and long-term mortality were compared with patients without MetS. Cox regression methods were used to assess the multivariable effect of MetS on long-term mortality. Of 41,146 patients, 12,228 (34%) had MetS. Patients with MetS experienced greater 30-day myocardial infarction (2.2% vs 1.8%, p = 0.013), whereas patients without MetS had a trend for greater 30-day mortality (3.0% vs 3.4%, p = 0.051) and greater in-hospital major bleeding (1.7% vs 2.4%, p <0.001). After a median follow-up of 5.62 years (Q1 2.03, Q3 8.89), patients with MetS experienced greater mortality (24% vs 19%, p <0.001). After adjustment, MetS was not an independent predictor of long-term mortality (hazard ratio 0.95 confidence interval 0.86 to 1.05, p = 0.35). In sensitivity analyses, MetS-Diabetic patients had the highest, and MetS-NonDiabetic obese patients had the lowest long-term mortality. One in 3 patients who underwent all-comer PCI presented with MetS and experienced greater long-term mortality compared with others. However, this association was lost after adjustment for baseline confounders, highlighting that MetS is a marker of risk after PCI. Our findings support the obesity paradox and confirm robust associations between diabetes mellitus and long-term mortality.


Subject(s)
Metabolic Syndrome , Percutaneous Coronary Intervention , Humans , Metabolic Syndrome/complications , Metabolic Syndrome/epidemiology , Male , Female , Middle Aged , Australia/epidemiology , Retrospective Studies , Aged , Risk Factors , Registries , Coronary Artery Disease/mortality , Coronary Artery Disease/surgery , Coronary Artery Disease/complications , Prevalence , Prognosis , Follow-Up Studies , Survival Rate/trends , Time Factors
5.
Cardiovasc Revasc Med ; 58: 1-6, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37500394

ABSTRACT

BACKGROUND: Current evidence suggests that percutaneous coronary intervention for unprotected left main coronary artery disease (LMPCI) in selected patients is a safe alternative to coronary artery bypass grafting. However, real-world long-term survival data is limited. METHODS: We analyzed 24,644 patients from the MIG (Melbourne Interventional Group) registry between 2005 and 2020. We compared baseline clinical and procedural characteristics, in-hospital and 30-day outcomes, and long-term survival between unprotected LMPCI and non-LMPCI among patients without ST-segment elevation myocardial infarction, cardiogenic shock, or cardiac arrest. RESULTS: Unprotected LMPCI patients (n = 185) were significantly older (mean age 72.0 vs. 64.6 years, p < 0.001), had higher prevalence of impaired ejection fraction (EF <50 %; 27.3 % vs. 14.9 %, p < 0.001) and lower estimated glomerular filtration rate < 60 ml/min/1.73m2 (40.9 % vs. 21.5 %, p < 0.001), and had greater use of intravascular ultrasound (21 % vs. 1 %, p < 0.001) and drug-eluting stents (p < 0.001). LMPCI was associated with longer hospital stay (4 days vs. 2 days, p < 0.001). There was no significant difference in other in-hospital outcomes, 30-day mortality (0.6 % vs. 0.6 %, p = 0.90), and major adverse cardiac events (1.7 % vs. 3 %, p = 0.28). Although the unadjusted Kaplan-Meier survival to 8 years was significantly less with LMPCI compared to non-LMPCI (p < 0.01), LMPCI was not a predictor of long-term survival up to 8 years after Cox regression analysis (HR 0.67, 95 % CI 0.40-1.13, p = 0.13). CONCLUSION: In this study, non-emergent unprotected LMPCI was uncommonly performed, and IVUS was underutilized. Despite greater co-morbidities, LMPCI patients had comparable 30-day outcomes to non-LMPCI, and LMPCI was not an independent predictor of long-term mortality.


Subject(s)
Coronary Artery Disease , Percutaneous Coronary Intervention , Humans , Aged , Treatment Outcome , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/therapy , Coronary Artery Disease/complications , Percutaneous Coronary Intervention/adverse effects , Registries , Risk Factors
6.
Heart Lung Circ ; 32(12): 1457-1464, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37945426

ABSTRACT

BACKGROUND: Left ventricular (LV) dysfunction and ischaemic heart disease (IHD) are common among women. However, women tend to present later and are less likely to receive guideline-directed medical therapy (GDMT) compared with men. METHODS: We analysed prospectively collected data (2005-2018) from a multicentre registry on GDMT 30 days after percutaneous coronary intervention in 13,015 patients with LV ejection fraction <50%. Guideline-directed medical therapy was defined as beta blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker±mineralocorticoid receptor antagonist. Long-term mortality was determined by linkage with the Australian National Death Index. RESULTS: Women represented 20% (2,634) of the total cohort. Mean age was 65±12 years. Women were on average >5 years, with higher body mass index and higher rates of hypertension, diabetes, renal dysfunction, prior stroke, and rheumatoid arthritis. Guideline-directed medical therapy was similar between sexes (73% vs 72%; p=0.58), although women were less likely to be on an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (80% vs 82%; p=0.02). Women were less likely to be on statin therapy (p<0.001) or a second antiplatelet agent (p=0.007). Women had higher unadjusted long-term mortality (25% vs 19%; p<0.001); however, there were no differences in long-term mortality between sexes on adjusted analysis (hazard ratio 0.99; 95% confidence interval 0.87-1.14; p=0.94). CONCLUSIONS: Rates of GDMT for LV dysfunction were high and similar between sexes; however, women were less likely to be on appropriate IHD secondary prevention. The increased unadjusted long-term mortality in women was attenuated in adjusted analysis, which highlights the need for optimisation of baseline risk to improve long-term outcomes of women with IHD and comorbid LV dysfunction.


Subject(s)
Coronary Artery Disease , Heart Failure , Myocardial Ischemia , Ventricular Dysfunction, Left , Humans , Female , Male , Middle Aged , Aged , Sex Characteristics , Australia/epidemiology , Myocardial Ischemia/complications , Myocardial Ischemia/drug therapy , Myocardial Ischemia/epidemiology , Coronary Artery Disease/drug therapy , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Adrenergic beta-Antagonists/therapeutic use , Ventricular Dysfunction, Left/drug therapy , Ventricular Dysfunction, Left/epidemiology , Stroke Volume/physiology , Angiotensin Receptor Antagonists/therapeutic use
7.
Hypertension ; 80(11): 2447-2454, 2023 11.
Article in English | MEDLINE | ID: mdl-37655489

ABSTRACT

BACKGROUND: Recent US guidelines recommend lower blood pressure (BP) targets in hypertension, but aggressive lowering of diastolic BP (DBP) can occur at the expense of myocardial perfusion, particularly in the presence of coronary artery disease. We sought to establish the long-term impact of low DBP on mortality among patients undergoing percutaneous coronary intervention with well-controlled systolic BP. METHODS: We analyzed data from 12 965 patients undergoing percutaneous coronary intervention between 2009 and 2018 from the Melbourne Interventional Group registry who had a preprocedural systolic BP of ≤140 mm Hg. Patients with ST-elevation myocardial infarction, cardiogenic shock, and out-of-hospital arrest were excluded. Patients were stratified into 5 groups according to preprocedural DBP: <50, 50 to 59, 60 to 69, 70 to 79, and ≥80 mm Hg. The primary outcome was long-term, all-cause mortality. Mortality data were derived from the Australian National Death Index. RESULTS: Patients with DBP<50 mm Hg were older with higher rates of diabetes, renal impairment, prior myocardial infarction, left ventricular dysfunction, peripheral and cerebrovascular disease (all P<0.001). Patients with DBP<50 mm Hg had higher 30-day (2.5% versus 0.7% for the other 4 quintiles; P<0.0001) and long-term mortality (median, 3.6 years; follow-up, 29% versus 11%; P<0.0001). Cox-regression analysis revealed that DBP<50 mm Hg was an independent predictor of long-term mortality (hazard ratio [HR], 1.55 [95% CI, 1.20-2.00]; P=0.001). CONCLUSIONS: In patients with well-controlled systolic BP undergoing percutaneous coronary intervention, low DBP (<50 mm Hg) is an independent predictor of long-term mortality.


Subject(s)
Myocardial Infarction , Percutaneous Coronary Intervention , Humans , Blood Pressure/physiology , Treatment Outcome , Australia , Percutaneous Coronary Intervention/adverse effects , Risk Factors , Registries
9.
JACC Case Rep ; 19: 101932, 2023 Aug 02.
Article in English | MEDLINE | ID: mdl-37593590

ABSTRACT

Coronary vasospasm is a relatively well-documented cause for ischemia and myocardial infarction in patients with nonobstructive coronary artery disease. Patients with coexisting eosinophilia present with severe manifestations and are often refractory to traditional therapies. There are few reported cases in the literature. We describe 3 cases occurring within 10 months. (Level of Difficulty: Intermediate.).

10.
BMJ Case Rep ; 16(6)2023 Jun 22.
Article in English | MEDLINE | ID: mdl-37348924

ABSTRACT

A young woman presented with a syncopal episode. As part of the work-up for her presentation, an MRI of the brain was performed which showed a small acute stroke. She subsequently had a further embolic-appearing stroke 9 months later. The initial investigations for the work-up of her strokes did not reveal any major abnormalities, including an unremarkable ECG and transthoracic echocardiogram (TTE). A transoesophageal echocardiogram (TOE) showed aneurysmal apical and mid-anteroseptal akinesis with mildly reduced left ventricular ejection fraction. Anomalous left coronary artery from the pulmonary artery (ALCAPA) was confirmed on coronary angiogram. Although ALCAPA presenting in adulthood is rare, our case highlights the value of TOE over TTE in the work-up of cryptogenic strokes, particularly in young patients with embolic strokes of undetermined source.


Subject(s)
Anomalous Left Coronary Artery , Bland White Garland Syndrome , Embolic Stroke , Ischemic Stroke , Female , Humans , Stroke Volume , Pulmonary Artery/abnormalities , Ventricular Function, Left
11.
JACC Cardiovasc Interv ; 16(4): 457-467, 2023 02 27.
Article in English | MEDLINE | ID: mdl-36858666

ABSTRACT

BACKGROUND: When patients with prior coronary artery bypass grafting (CABG) undergo percutaneous coronary intervention (PCI), targeting the native vessel is preferred. Studies informing such recommendations are based predominantly on saphenous vein graft (SVG) PCI. There are few data regarding arterial graft intervention, particularly to a radial artery (RA) graft. OBJECTIVES: The aim of this study was to report the characteristics of arterial graft stenoses and evaluate the feasibility of RA PCI. METHODS: This study included 2,780 consecutive patients with prior CABG undergoing PCI between 2005 and 2018 who were prospectively enrolled in the MIG (Melbourne Interventional Group) registry. Data were stratified by PCI target vessel. RA graft PCI was compared with both native vessel (native PCI) and SVG PCI. Internal mammary graft PCI data were reported. The primary outcome was 3-year mortality. RESULTS: Overall, 1,928 patients (69.4%) underwent native PCI, 716 (25.6%) SVG PCI, 86 (3.1%) RA PCI, and 50 (1.8%) internal mammary graft PCI. Compared with SVG PCI, the RA PCI cohort presented earlier after CABG, less frequently had acute coronary syndrome, and more commonly had ostial or distal anastomosis intervention (P < 0.005 for all). Compared with patients who underwent native PCI, those who underwent RA PCI were more likely to have diabetes and peripheral vascular disease (P < 0.001 for both) and to present with non-ST-segment elevation myocardial infarction (P = 0.010). The RA PCI group had no perforations or in-hospital myocardial infarctions, though no significant difference was found in periprocedural outcomes compared with either native or SVG PCI. No differences were found between RA PCI and either native or SVG PCI in 30-day outcomes or 3-year mortality. CONCLUSIONS: Presenting and lesion characteristics differed between patients undergoing arterial compared with SVG PCI, implying a varied pathogenesis of graft stenosis. RA PCI appears feasible, safe, and where anatomically suitable, may be a viable alternative to native PCI.


Subject(s)
Acute Coronary Syndrome , Non-ST Elevated Myocardial Infarction , Percutaneous Coronary Intervention , Humans , Radial Artery , Treatment Outcome , Anastomosis, Surgical , Constriction, Pathologic
12.
Am J Cardiol ; 191: 125-132, 2023 03 15.
Article in English | MEDLINE | ID: mdl-36682080

ABSTRACT

Myocardial infarction complicated by cardiogenic shock (MI-CS) has a poor prognosis, even with early revascularization. Previously, intra-aortic balloon pump (IABP) use was thought to improve outcomes, but the IABP-SHOCK-II (Intra-aortic Balloon Pump in Cardiogenic Shock-II study) trial found no survival benefit. We aimed to determine the trends in IABP use in patients who underwent percutaneous intervention over time. Data were taken from patients in the Melbourne Interventional Group registry (2005 to 2018) with MI-CS who underwent percutaneous intervention. The primary outcome was the trend in IABP use over time. The secondary outcomes included 30-day mortality and major adverse cardiovascular and cerebrovascular events (MACCEs). Of the 1,110 patients with MI-CS, IABP was used in 478 patients (43%). IABP was used more in patients with left main/left anterior descending culprit lesions (62% vs 46%), lower ejection fraction (<35%; 18% vs 11%), and preprocedural inotrope use (81% vs 73%, all p <0.05). IABP use was associated with higher bleeding (18% vs 13%) and 30-day MACCE (58% vs 51%, both p <0.05). The rate of MI-CS per year increased over time; however, after 2012, there was a decrease in IABP use (p <0.001). IABP use was a predictor of 30-day MACCE (odds ratio 1.6, 95% confidence interval 1.18 to 2.29, p = 0.003). However, IABP was not associated with in-hospital, 30-day, or long-term mortality (45% vs 47%, p = 0.44; 46% vs 50%, p = 0.25; 60% vs 62%, p = 0.39). In conclusion, IABP was not associated with reduced short- or long-term mortality and was associated with increased short-term adverse events. IABP use is decreasing but is predominately used in sicker patients with greater myocardium at risk.


Subject(s)
Heart-Assist Devices , Myocardial Infarction , Percutaneous Coronary Intervention , Humans , Shock, Cardiogenic/epidemiology , Shock, Cardiogenic/etiology , Shock, Cardiogenic/therapy , Myocardial Infarction/complications , Myocardial Infarction/epidemiology , Intra-Aortic Balloon Pumping , Heart-Assist Devices/adverse effects , Registries , Treatment Outcome , Percutaneous Coronary Intervention/adverse effects
13.
Emerg Med J ; 40(2): 101-107, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35473753

ABSTRACT

BACKGROUND: An adverse interaction whereby opioids impair and delay the gastrointestinal absorption of oral P2Y12 inhibitors has been established, however the clinical significance of this in acute coronary syndrome (ACS) is uncertain. We sought to characterise the relationship between prehospital opioid dose and clinical outcomes in patients with ACS. METHODS: Patients given opioid treatment by emergency medical services (EMS) with ACS who underwent percutaneous coronary intervention (PCI) between 1 January 2014 and 31 December 2018 were included in this retrospective cohort analysis using data linkage between the Ambulance Victoria, Victorian Cardiac Outcomes Registry and Melbourne Interventional Group databases. Patients with cardiogenic shock, out-of-hospital cardiac arrest and fibrinolysis were excluded. The primary end point was the risk-adjusted odds of 30-day major adverse cardiac events (MACE) between patients who received opioids and those that did not. RESULTS: 10 531 patients were included in the primary analysis. There was no significant difference in 30-day MACE between patients receiving opioids and those who did not after adjusting for key patient and clinical factors. Among patients with ST-elevation myocardial infarction (STEMI), there were significantly more patients with thrombolysis in myocardial infarction (TIMI) 0 or 1 flow pre-PCI in a subset of patients with high opioid dose versus no opioids (56% vs 25%, p<0.001). This remained significant after adjusting for known confounders with a higher predicted probability of TIMI 0/1 flow in the high versus no opioid groups (33% vs 11%, p<0.001). CONCLUSIONS: Opioid use was not associated with 30-day MACE. There were higher rates of TIMI 0/1 flow pre-PCI in patients with STEMI prescribed opioids. Future prospective research is required to verify these findings and investigate alternative analgesia for ischaemic chest pain.


Subject(s)
Acute Coronary Syndrome , Emergency Medical Services , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , Acute Coronary Syndrome/therapy , Retrospective Studies , Analgesics, Opioid/therapeutic use , Treatment Outcome
14.
Intern Med J ; 53(8): 1376-1382, 2023 08.
Article in English | MEDLINE | ID: mdl-35670161

ABSTRACT

BACKGROUND: Previous large multi-centre randomised controlled trials have not provided clear benefit with routine intracoronary thrombus aspiration (TA) as an adjunct to primary percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI). AIM: To determine whether there is a difference in outcomes with the use of manual TA prior to PCI, compared with PCI alone in a cohort of patients with STEMI. METHODS: We analysed data from 6270 consecutive patients undergoing primary PCI for STEMI prospectively enrolled in the Melbourne Interventional Group registry between 2007 and 2018. Multivariable analysis was performed to determine predictors of 30-day major adverse cardiovascular and cerebrovascular events (MACCE) and long-term mortality. RESULTS: We compared 1621 (26%) patients undergoing primary PCI with TA to 4649 (74%) patients undergoing PCI alone. Male gender (81% vs 78%; P < 0.01), younger age (61 vs 63 years; P = 0.03), GP-IIb/IIIa use (76% vs 58%, P < 0.01), and current smoking (40% vs 36%; P < 0.01) were more common in the TA group. TA was more likely to be used in patients with complex lesions (83% vs 66%; P < 0.01) with TIMI 0 flow (77% vs 56%; P < 0.01). No significant difference in post-procedural TIMI flow, stroke, 30-day mortality, or long-term mortality were identified. Multivariable analysis demonstrated a reduction in 30-day MACCE (hazard ratio (HR) 0.75; confidence interval (CI) 0.63-0.89; P < 0.01) in the TA group, but was not associated with long-term mortality (HR 0.98; CI 0.85-1.1; P = 0.73). CONCLUSION: The use of TA in patients undergoing primary PCI for STEMI was not associated with improved short or long-term mortality when compared with PCI alone.


Subject(s)
Coronary Thrombosis , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , Male , Middle Aged , Coronary Thrombosis/etiology , Percutaneous Coronary Intervention/adverse effects , ST Elevation Myocardial Infarction/surgery , Thrombectomy , Treatment Outcome , Clinical Trials as Topic
15.
Nat Commun ; 13(1): 6558, 2022 11 02.
Article in English | MEDLINE | ID: mdl-36323665

ABSTRACT

mRNA translation is tightly regulated to preserve cellular homeostasis. Despite extensive biochemical, genetic, and structural studies, a detailed understanding of mRNA translation regulation is lacking. Imaging methodologies able to resolve the binding dynamics of translation factors at single-cell and single-mRNA resolution were necessary to fully elucidate regulation of this paramount process. Here live-cell spectroscopy and single-particle tracking were combined to interrogate the binding dynamics of endogenous initiation factors to the 5'cap. The diffusion of initiation factors (IFs) changed markedly upon their association with mRNA. Quantifying their diffusion characteristics revealed the sequence of IFs assembly and disassembly in cell lines and the clustering of translation in neurons. This approach revealed translation regulation at high spatial and temporal resolution that can be applied to the formation of any endogenous complex that results in a measurable shift in diffusion.


Subject(s)
Peptide Initiation Factors , Protein Biosynthesis , RNA, Messenger/metabolism , Peptide Initiation Factors/genetics , RNA Caps/metabolism , Peptide Chain Initiation, Translational
16.
Cell ; 185(18): 3390-3407.e18, 2022 09 01.
Article in English | MEDLINE | ID: mdl-36055200

ABSTRACT

Chemical synapses between axons and dendrites mediate neuronal intercellular communication. Here, we describe a synapse between axons and primary cilia: the axo-ciliary synapse. Using enhanced focused ion beam-scanning electron microscopy on samples with optimally preserved ultrastructure, we discovered synapses between brainstem serotonergic axons and the primary cilia of hippocampal CA1 pyramidal neurons. Functionally, these cilia are enriched in a ciliary-restricted serotonin receptor, the 5-hydroxytryptamine receptor 6 (5-HTR6). Using a cilia-targeted serotonin sensor, we show that opto- and chemogenetic stimulation of serotonergic axons releases serotonin onto cilia. Ciliary 5-HTR6 stimulation activates a non-canonical Gαq/11-RhoA pathway, which modulates nuclear actin and increases histone acetylation and chromatin accessibility. Ablation of this pathway reduces chromatin accessibility in CA1 pyramidal neurons. As a signaling apparatus with proximity to the nucleus, axo-ciliary synapses short circuit neurotransmission to alter the postsynaptic neuron's epigenetic state.


Subject(s)
Axons/physiology , Chromatin/chemistry , Cilia , Synapses , Cell Nucleus/metabolism , Chromatin/metabolism , Cilia/metabolism , Hippocampus/cytology , Hippocampus/physiology , Serotonin/metabolism , Signal Transduction , Synapses/physiology
17.
Science ; 376(6591): 377-382, 2022 04 22.
Article in English | MEDLINE | ID: mdl-35446649

ABSTRACT

Cytotoxic T lymphocytes (CTLs) and natural killer cells kill virus-infected and tumor cells through the polarized release of perforin and granzymes. Perforin is a pore-forming toxin that creates a lesion in the plasma membrane of the target cell through which granzymes enter the cytosol and initiate apoptosis. Endosomal sorting complexes required for transport (ESCRT) proteins are involved in the repair of small membrane wounds. We found that ESCRT proteins were precisely recruited in target cells to sites of CTL engagement immediately after perforin release. Inhibition of ESCRT machinery in cancer-derived cells enhanced their susceptibility to CTL-mediated killing. Thus, repair of perforin pores by ESCRT machinery limits granzyme entry into the cytosol, potentially enabling target cells to resist cytolytic attack.


Subject(s)
Endosomal Sorting Complexes Required for Transport , Membrane Glycoproteins , Endosomal Sorting Complexes Required for Transport/genetics , Endosomal Sorting Complexes Required for Transport/metabolism , Granzymes/metabolism , Membrane Glycoproteins/metabolism , Perforin/genetics , Perforin/metabolism , Pore Forming Cytotoxic Proteins/genetics , Pore Forming Cytotoxic Proteins/metabolism , T-Lymphocytes, Cytotoxic/metabolism
18.
Heart Lung Circ ; 31(5): 638-646, 2022 May.
Article in English | MEDLINE | ID: mdl-35125322

ABSTRACT

OBJECTIVES: Approximately 5-10% of patients presenting for percutaneous coronary intervention (PCI) have concurrent atrial fibrillation (AF). To what extent AF portends adverse long-term outcomes in these patients remains to be defined. METHODS: We analysed data from the multicentre Melbourne Interventional Group Registry from 2014-2018. Patients were identified as being in AF or sinus rhythm (SR) at the commencement of PCI. The primary endpoint was long-term mortality, obtained via linkage with the National Death Index. RESULTS: 13,286 procedures were included, with 800 (6.0%) patients in AF and 12,486 (94.0%) in SR. Compared to SR, patients with AF were older (72.9±10.9 vs 64.1±12.0 p<0.001) and more likely to have comorbidities including diabetes mellitus (31.3% vs 25.0% p<0.001), hypertension (74.4% vs 65.1% p<0.001) and moderate to severe left ventricular systolic dysfunction (36.6% vs 19.5% p<0.001). Atrial fibrillation was associated with an increased risk of in-hospital mortality (11.0% vs 2.5% p<0.001) and MACE (composite of all-cause mortality, myocardial infarction, or target vessel revascularisation) (11.9% vs 4.2% p<0.001). In-hospital major bleeding was more common in the AF group (3.1% vs 1.0% p<0.001). On Cox proportional hazards modelling, AF was an independent predictor of long-term mortality (adjusted HR 1.38 95% CI 1.11-1.72 p<0.004) at a mean follow-up of 2.3±1.5 years. CONCLUSIONS: Preprocedural AF is common among patients presenting for PCI. Preprocedural AF is associated with high-rates of comorbid illnesses and portends higher risk of short- and long-term outcomes including mortality underscoring the need for careful evaluation of its risks prior to PCI.


Subject(s)
Atrial Fibrillation , Myocardial Infarction , Percutaneous Coronary Intervention , Atrial Fibrillation/complications , Hemorrhage/etiology , Humans , Myocardial Infarction/etiology , Percutaneous Coronary Intervention/methods , Registries , Treatment Outcome
19.
Am J Cardiol ; 168: 39-46, 2022 04 01.
Article in English | MEDLINE | ID: mdl-35115134

ABSTRACT

Unprotected left main (LM) percutaneous coronary intervention (PCI) at centers without onsite cardiac surgery remains controversial. We aimed to evaluate the effect of onsite cardiac surgery on short-term and long-term outcomes in patients who had unprotected LM PCI. We analyzed Victorian Cardiac Outcomes Registry data on consecutive patients who had unprotected LM PCI at cardiac surgical centers (SCs) and non-SCs (NSCs) between January 2014 to December 2018. Compared with the SC group (n = 594, 81%), the NSC group (n = 136) were younger (69 vs 72 years) and presented with more ST-elevation myocardial infarction (35% vs 16%) and cardiogenic shock (25% vs 15%), with higher rates of preprocedural intubation (17% vs 11%) and mechanical circulatory support (20% vs 9.3%), all p <0.01. Unadjusted in-hospital mortality (23% vs 11.4%), and 30-day major adverse cardiac events (composite of mortality, myocardial infarction, stent thrombosis, or unplanned revascularization) (26% vs 16%) were higher in NSC patients, all p <0.01. However, following multivariable adjustment, SC was neither a predictor of in-hospital mortality (odds ratio 0.68, 95% confidence interval [CI] 0.32 to 1.43, p = 0.31), 30-day mortality (odds ratio 0.70, 95% CI 0.33 to 1.48, p = 0.35) nor long-term survival at 60 months (hazard ratio 0.88, 95% CI 0.62 to 1.27, p = 0.51). Propensity score analysis confirmed the neutral effect of onsite cardiac surgery on long-term survival (hazard ratio 0.99, 95% CI 0.66 to 1.50, p = 0.97). In conclusion, patients who underwent unprotected LM PCI at NSCs presented with greater acuity of illness. Despite this, the availability of onsite cardiac surgical support was not associated with in-hospital, 30-day, or long-term outcomes underscoring the safety of LM PCI in NSCs.


Subject(s)
Cardiac Surgical Procedures , Coronary Artery Disease , Myocardial Infarction , Percutaneous Coronary Intervention , Coronary Artery Disease/surgery , Humans , Percutaneous Coronary Intervention/adverse effects , Risk Factors , Treatment Outcome
20.
Cardiovasc Revasc Med ; 41: 136-141, 2022 08.
Article in English | MEDLINE | ID: mdl-35165049

ABSTRACT

BACKGROUND: Primary percutaneous coronary intervention (PCI) for patients with ST-elevation myocardial infarction (STEMI) is recommended within 90 min of first medical contact. Those without pre-hospital notification (PN) are less likely to meet reperfusion targets and are an understudied subset of the STEMI population. METHODS: An observational cohort study from a multicentre PCI registry of consecutive patients undergoing primary PCI for STEMI between 2012 and 2017. Exclusion criteria included out-of-hospital cardiac arrest, prior thrombolysis, symptom onset >12 h prior, and cardiogenic shock. RESULTS: 2519 patients were included: 1392 (55.3%) without PN (no-PN group) and 1127 (44.7%) with PN (PN group). Those without PN had longer median DTBT (78 min vs 51 min, p < 0.001) and STBT (206 min vs 161 min, p < 0.001), with only 55% meeting DTBT targets out-of-hours in the no-PN group. No-PN patients had lower rates of AHA/ACC type B2/C lesions, GP IIb/IIIa use, aspiration thrombectomy and had smaller stent diameter (all p ≤ 0.003), suggesting smaller areas of ischemic myocardium. There were no significant differences in 30-day MACE (no-PN 5.6% vs PN 6.5%, p = 0.36) or long-term National Death Index linked mortality (no-PN 6.2% vs PN 7.9%, p = 0.09). Lack of PN did not independently predict long-term mortality. CONCLUSION: Despite comparably excellent outcomes overall, those without PN had longer ischemic times and were less likely to meet DTBT targets, especially after hours. Ischemic times may be a better evaluation of PN networks than hard clinical outcomes, and efficient systems of care tailored to the individual health service are essential to ensure timely reperfusion of patients with STEMI.


Subject(s)
Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Hospitals , Humans , Percutaneous Coronary Intervention/adverse effects , Reperfusion , ST Elevation Myocardial Infarction/diagnostic imaging , ST Elevation Myocardial Infarction/therapy , Time Factors , Treatment Outcome
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